Analytic and Clinical Performance of cobas HPV Testing in Anal Specimens from HIV-Positive Men Who Have Sex with Men

PubMed Central

Follansbee, Stephen; Borgonovo, Sylvia; Tokugawa, Diane; Sahasrabuddhe, Vikrant V.; Chen, Jie; Lorey, Thomas S.; Gage, Julia C.; Fetterman, Barbara; Boyle, Sean; Sadorra, Mark; Tang, Scott Dahai; Darragh, Teresa M.; Castle, Philip E.

2014-01-01

Anal human papillomavirus (HPV) infections are common, and the incidence of anal cancer is high in HIV-infected men who have sex with men (MSM). To evaluate the performance of HPV assays in anal samples, we compared the cobas HPV test (cobas) to the Roche Linear Array HPV genotyping assay (LA) and cytology in HIV-infected MSM. Cytology and cobas and LA HPV testing were conducted for 342 subjects. We calculated agreement between the HPV assays and the clinical performance of HPV testing and HPV genotyping alone and in combination with anal cytology. We observed high agreement between cobas and LA, with cobas more likely than LA to show positive results for HPV16, HPV18, and other carcinogenic types. Specimens testing positive in cobas but not in LA were more likely to be positive for other markers of HPV-related disease compared to those testing negative in both assays, suggesting that at least some of these were true positives for HPV. cobas and LA showed high sensitivities but low specificities for the detection of anal intraepithelial neoplasia grade 2/3 (AIN2/3) in this population (100% sensitivity and 26% specificity for cobas versus 98.4% sensitivity and 28.9% specificity for LA). A combination of anal cytology and HPV genotyping provided the highest accuracy for detecting anal precancer. A higher HPV load was associated with a higher risk of AIN2/3 with HPV16 (Ptrend < 0.001), HPV18 (Ptrend = 0.07), and other carcinogenic types (Ptrend < 0.001). We demonstrate that cobas can be used for HPV detection in anal cytology specimens. Additional tests are necessary to identify men at the highest risk of anal cancer among those infected with high-risk HPV. PMID:24899025

Prevalence of oral and oropharyngeal human papillomavirus in a sample of South African men: a pilot study.

PubMed

Davidson, Christy Lana; Richter, Karin Louise; Van der Linde, Mike; Coetsee, Judy; Boy, Sonja Catharina

2014-03-26

Human papillomavirus (HPV) infection is well known to be associated with head and neck cancers (HNCs). HPV-associated HNCs are related to sexual behaviour, particularly the lifetime number of oral sex partners, but the epidemiology of oral and oropharyngeal HPV in South African men has not yet been studied. To determine the oral and oropharyngeal HPV strain prevalence and associated factors in a selected male population in Pretoria, South Africa (SA). Male factory workers were recruited. Oral rinse and gargle samples were tested for 37 HPV types using the Linear Array HPV Genotyping Test (Roche Molecular Systems). A questionnaire was used to obtain information regarding age, medical conditions, substance and alcohol use and sexual behaviour. HIV testing was optional. The HPV prevalence was 5.6% among men (N=125) aged 17 - 64 years. High-risk HPV (hrHPV) types 16 and 68 were found in two men. Oral sex seemed to be an uncommon practice in the majority of respondents, but the two respondents with hrHPV did practise oral sex. There was a statistically significant association between HPV infection and an increased number of sexual partners (p=0.027), but not between HPV and substance use, HIV status or clinical mucosal pathology. The prevalence of oral and oropharyngeal HPV was lower than reported in other countries. An association between oral HPV and having multiple sexual partners was found. A larger nationwide study would give a more representative view of the burden of oral and oropharyngeal HPV infection in SA.

Comparison of anal HPV natural history among men by country of residence: Brazil, Mexico, and the United States.

PubMed

Sudenga, Staci L; Nyitray, Alan G; Torres, B Nelson; Silva, Roberto; Villa, Luisa; Lazcano-Ponce, Eduardo; Abrahamsen, Martha; Baggio, Maria Luiza; Salmeron, Jorge; Quiterio, Manuel; Giuliano, Anna R

2017-07-01

Globally, anal cancer incidence is rare, but is increasing in some world regions. Our objective was to assess differences in anal HPV natural history in three countries. Men aged 18-70 years were recruited from the US (n = 634), Mexico (n = 665), and Brazil (n = 731). Anal specimens were collected every six-months. HPV genotyping was assessed by Linear Array. Anal HPV prevalence was compared using the Fisher's exact test. HPV infection incidence rates (IR) and 95% confidence intervals (CI) were calculated. Any anal HPV prevalence was highest among men from Brazil (24%) compared to Mexico (15%) and the US (15%). When stratified by sexual history, the prevalence of any HPV among MSM/MSMW was 43%, 37%, and 45% and 9%, 12%, and 10% for MSW from Brazil, Mexico, and US, respectively. Any HPV incidence was significantly higher among men from Brazil compared to US men (IRR = 2.4, 95% CI = 1.7-3.4) and comparable between men from Mexico and the US (IRR = 1.2, 95% CI = 0.8-1.8). Men in Brazil and Mexico often have similar, if not higher incidence of anal HPV compared to men from the U.S., and may benefit from gender neutral HPV vaccine policies. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Human Papillomavirus Genotype Prevalence in Invasive Penile Cancers from a Registry-Based United States Population

PubMed Central

Hernandez, Brenda Y.; Goodman, Marc T.; Unger, Elizabeth R.; Steinau, Martin; Powers, Amy; Lynch, Charles F.; Cozen, Wendy; Saber, Maria Sibug; Peters, Edward S.; Wilkinson, Edward J.; Copeland, Glenn; Hopenhayn, Claudia; Huang, Youjie; Watson, Meg; Altekruse, Sean F.; Lyu, Christopher; Saraiya, Mona

2013-01-01

Background: Human papillomavirus (HPV) is estimated to play an etiologic role in 40–50% of penile cancers worldwide. Estimates of HPV prevalence in U.S. penile cancer cases are limited. Methods: HPV DNA was evaluated in tumor tissue from 79 invasive penile cancer patients diagnosed in 1998–2005 within the catchment areas of seven U.S. cancer registries. HPV was genotyped using PCR-based Linear Array and INNO-LiPA assays and compared by demographic, clinical, and pathologic characteristics and survival. Histological classification was also obtained by independent pathology review. Results: HPV DNA was present in 50 of 79 (63%) of invasive penile cancer cases. Sixteen viral genotypes were detected. HPV 16, found in 46% (36/79) of all cases (72% of HPV-positive cases) was the most prevalent genotype followed equally by HPV 18, 33, and 45, each of which comprised 5% of all cases. Multiple genotypes were detected in 18% of viral positive cases. HPV prevalence did not significantly vary by age, race/ethnicity, population size of geographic region, cancer stage, histology, grade, penile subsite, or prior cancer history. Penile cases diagnosed in more recent years were more likely to be HPV-positive. Overall survival did not significantly vary by HPV status. Conclusion: The relatively high prevalence of HPV in our study population provides limited evidence of a more prominent and, possibly, increasing role of infection in penile carcinogenesis in the U.S. compared to other parts of the world. PMID:24551592

Global Improvement in Genotyping of Human Papillomavirus DNA: the 2011 HPV LabNet International Proficiency Study

PubMed Central

Eklund, Carina; Forslund, Ola; Wallin, Keng-Ling

2014-01-01

Accurate and internationally comparable human papillomavirus (HPV) DNA genotyping is essential for HPV vaccine research and for HPV surveillance. The HPV Laboratory Network (LabNet) has designed international proficiency studies that can be issued regularly and in a reproducible manner. The 2011 HPV genotyping proficiency panel contained 43 coded samples composed of purified plasmids of 16 HPV types (HPV6, -11, -16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, -68a, and -68b) and 3 extraction controls. Tests that detected 50 IU of HPV16 and HPV18 and 500 genome equivalents for the other 14 HPV types in both single and multiple infections were considered proficient. Ninety-six laboratories worldwide submitted 134 data sets. Twenty-five different HPV genotyping assay methods were used, including the Linear Array, line blot/INNO-LiPA, PapilloCheck, and PCR Luminex assays. The major oncogenic HPV types, HPV16 and HPV18, were proficiently detected in 97.0% (113/116) and 87.0% (103/118) of the data sets, respectively. In 2011, 51 data sets (39%) were 100% proficient for the detection of at least one HPV type, and 37 data sets (28%) were proficient for all 16 HPV types; this was an improvement over the panel results from the 2008 and 2010 studies, when <25 data sets (23% and 19% for 2008 and 2010, respectively) were fully proficient. The improvement was also evident for the 54 laboratories that had also participated in the previous proficiency studies. In conclusion, a continuing global proficiency program has documented worldwide improvement in the comparability and reliability of HPV genotyping assay performances. PMID:24478473

The EVVA Cohort Study: Anal and Cervical Type-Specific Human Papillomavirus Prevalence, Persistence, and Cytologic Findings in Women Living With HIV.

PubMed

de Pokomandy, Alexandra; Kaufman, Elaina; de Castro, Christina; Mayrand, Marie-Hélène; Burchell, Ann N; Klein, Marina; Charest, Louise; Auger, Manon; Rodrigues-Coutlée, Sophie; Coutlée, François

2017-08-15

The risk of anal cancer due to high-risk human papillomavirus (HR-HPV) is higher in women living with human immunodeficiency virus (HIV) than in the general population. We present findings of cervical and anal HPV and cytologic tests at baseline in the EVVA cohort study and HPV persistence data 6 months after baseline. Semiannual visits included questionnaires, chart reviews, cervical/anal cytologic and cervical/anal HPV testing for 2 years. Genotyping for 36 HPV genotypes was performed using the Roche Linear Array HPV genotyping test. A total of 151 women living with HIV were recruited. At baseline, 75% had anal HPV, 51% had anal HR-HPV, 50% had cervical HPV, and 29% had cervical HR-HPV. Anal HPV-16 and HPV-51 were more frequent in women born in Canada (31% and 29%, respectively, compared with ≤16% for other women). Most anal HR-HPV types detected at 6 months (57%-93%) were persistent from baseline. Findings of anal cytologic tests were abnormal for 37% of women. Anal HPV is highly prevalent in women living with HIV, and type distribution varies by place of birth. High-resolution anoscopy was indicated in more than one third of results. As anal cancer is potentially preventable, these important findings need to be considered when selecting the best approach for anal cancer screening programs. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

High Risk Human Papillomavirus Persistence Among HIV-infected Young Women in South Africa

PubMed Central

Adler, David; Wallace, Melissa; Bennie, Thola; Abar, Beau; Sadeghi, Rokhsanna; Meiring, Tracy; Williamson, Anna-Lise; Bekker, Linda-Gail

2015-01-01

Objectives Persistence of infection with high-risk Human papillomaviruses (HR-HPV) increases the risk of incident and progressive precancerous lesions of the cervix. Rates of HR-HPV persistence have been shown to be increased among HIV-infected adult women, however there is a paucity of literature addressing HPV persistence in the young HIV-infected population. We compared rates of HR-HPV persistence between HIV-infected and HIV-uninfected young women. Methods We obtained self-collected vaginal swabs at six-month intervals from 50 HIV-uninfected and 33 HIV-infected young women recruited through a community youth center (age 17-21 years) and compared rates of HR-HPV persistence. HR-HPV testing was conducted using the Roche’s Linear Array® HPV Test. Results Eighty-three prevalent (upon baseline testing) and incident (upon subsequent testing) individual HR-HPV infections were identified among 43 members of the cohort (23 HIV-uninfected and 20 HIV-infected). At twelve months, 19% of baseline HR-HPV infections continued to be present with a statistically significant difference between HIV-uninfected and HIV-infected participants (4% versus 31%; p=0.01). Conclusions HIV-infected young women in our cohort had a seven-fold increased rate of persistence of HR-HPV overall at 12 months indicating an increased risk for incident and progressive precancerous lesions. Identification of persistent infection with HR-HPV may complement cytological findings in determining the need for colposcopy. PMID:25697074

The epidemiology of oral HPV infection among a multinational sample of healthy men

PubMed Central

Kreimer, Aimee R.; Villa, Alessandro; Nyitray, Alan G.; Abrahamsen, Martha; Papenfuss, Mary; Smith, Danelle; Hildesheim, Allan; Villa, Luisa L; Lazcano-Ponce, Eduardo; Giuliano, Anna R.

2011-01-01

Background Oral human papillomavirus type-16 (HPV16) infection is a risk factor for oropharyngeal cancer. We examined oral HPV infection among healthy men. Methods Oral rinse/gargle specimens and questionnaire data were collected from 1,688 healthy men aged 18 to 74 (median 31 years), from the United States, Mexico, and Brazil. HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59 and non-carcinogenic HPV types were detected using Roche Linear Array. Results Oral HPV DNA was detected in 67 of 1680 (4.0%, 95%CI 3.1% to 5.0%) ß-globin positive specimens; carcinogenic HPVs were detected in 1.3% (95%CI 0.8% to 2.0%; n=22) and HPV16 was the most commonly detected carcinogenic HPV type (0.6%, 95%CI 0.2% to 1.1%; n=10). The prevalence of oral HPV infection was similar by country except for HPV55, which had notably higher prevalence in Mexico (3.0%) than Brazil (0%) or the US (0.2%). Oral HPV prevalence non-significantly increased over increasing age categories (p for trend 0.096). The strongest predictor of oral HPV was current tobacco use, which increased the odds 2.5-fold (95%CI 1.4–4.4). Oral sexual behaviors were not associated with oral HPV infection. Conclusions Oral HPV16 infection was rare in healthy men, especially at younger ages, and was positively associated with current tobacco use. Impact Oral HPV appears to be ~10 fold less prevalent than infection at genital sites in men (4% vs. ~40%, respectively). It remains unclear whether this reflects reduced exposure or if the oral region is more resistant to HPV infection compared to anogenital sites. PMID:21148755

Evaluation of the clinical performance of the Abbott RealTime High-Risk HPV for carcinogenic HPV detection.

PubMed

Halfon, Philippe; Benmoura, Dominique; Agostini, Aubert; Khiri, Hacene; Penaranda, Guillaume; Martineau, Agnes; Blanc, Bernard

2010-08-01

Abbott RealTime (RT) High-Risk (HR) HPV assay is a new qualitative real-time polymerase chain reaction (PCR) based assay for the detection of 14 HR HPV DNA. The assay can differentiate between the infection by HPV 16, HPV 18 and non-HPV 16/18 types through the distinct fluorescent labels on the type specific probes. To evaluate the clinical performance of the Abbott RT HR HPV test, in comparison with biopsy, Hybrid Capture II (HCII), and Linear Array (LA), for detection of high-grade disease (CIN2+). The study population consisted of 143 women who were included in three referral gynecology clinics in Marseilles (France) between March 2007 and June 2008. The clinical performance of the RT HR HPV assay, performed on the fully automated m2000 system, was compared with HCII and LA. HR HPV positivity rate was similar for all tests (Abbott RT HR HPV and HCII, 62%, and LA 63%). All tests had high sensitivities and negative predictive values for CIN2+ detection (>90%). The agreement between HCII and Abbott RT HR HPV, and between HCII and LA were 93% (k=0.85) and 96% (k=0.91) respectively. As expected, HPV16 or HPV18 positivity was greater in advanced grades of disease, especially in CIN2+ patients: 85% in CIN2+ vs. 33% in

The Effect of Cryotherapy on Human Papillomavirus Clearance among HIV-positive Women in Lusaka, Zambia

PubMed Central

Katundu, Katundu; Bateman, Allen C.; Pfaendler, Krista S.; Mwanahamuntu, Mulindi H.; Kapambwe, Sharon; Vermund, Sten H.; Sahasrabuddhe, Vikrant V.; Msadabwe, Susan C.; Stringer, Jeffrey S.A.; Parham, Groesbeck P.; Chibwesha, Carla J.

2015-01-01

Objective We sought to investigate the progression of human papillomaviruses (HPV) infection in HIV-positive women after cryotherapy. Methods We examined changes in detection of high-risk HPV (hrHPV) cervical infections among HIV-infected women over a 12-week period following cryotherapy using stored specimens from a cohort study conducted between June 2009 and March 2011 in Lusaka, Zambia. Samples from visits at baseline and weeks 4, 8, and 12 were tested using the Roche Linear Array assay. Results A total of 89 women were included in the analysis. The median age was 32 years (interquartile range [IQR]: 28–36 years). The median CD4+ cell count was 350 cells/μL (IQR: 214–470 cells/μL) and 66% of women were receiving antiretroviral therapy. At baseline, the prevalence of hrHPV was 91% (95% confidence interval [CI]: 83–95%). HPV45 was the most common HPV type, present in (30%) women, followed by HPV16 (27%), HPV18 (27%), HPV51 (20%), and HPV58 (22%). Among women with valid results both at baseline and 12 weeks, 17/67 (25%) cleared their initial hrHPV infection within 12 weeks of treatment, though 65% (11/17) had new hrHPV types detected. Conclusions Cryotherapy led to clearance of 25% of hrHPV infections within 12 weeks of treatment. However, hrHPV infection remained persistent in most women and new hrHPV types were detected often, explaining the high rate of persistence and recurrence of cervical disease in this population. Continued efforts to scale-up HPV vaccination and cervical screening should remain a priority in high HIV burden settings such as Zambia. PMID:26125097

Sequential Acquisition of Anal Human Papillomavirus (HPV) Infection Following Genital Infection Among Men Who Have Sex With Women: The HPV Infection in Men (HIM) Study

PubMed Central

Pamnani, Shitaldas J.; Nyitray, Alan G.; Abrahamsen, Martha; Rollison, Dana E.; Villa, Luisa L.; Lazcano-Ponce, Eduardo; Huang, Yangxin; Borenstein, Amy; Giuliano, Anna R.

2016-01-01

Background. The purpose of this study was to assess the risk of sequential acquisition of anal human papillomavirus (HPV) infection following a type-specific genital HPV infection for the 9-valent vaccine HPV types and investigate factors associated with sequential infection among men who have sex with women (MSW). Methods. Genital and anal specimens were available for 1348 MSW participants, and HPV genotypes were detected using the Roche Linear Array assay. Sequential risk of anal HPV infection was assessed using hazard ratios (HRs) among men with prior genital infection, compared with men with no prior genital infection, in individual HPV type and grouped HPV analyses. Results. In individual analyses, men with prior HPV 16 genital infections had a significantly higher risk of subsequent anal HPV 16 infections (HR, 4.63; 95% confidence interval [CI], 1.41–15.23). In grouped analyses, a significantly higher risk of sequential type-specific anal HPV infections was observed for any of the 9 types (adjusted HR, 2.80; 95% CI, 1.32–5.99), high-risk types (adjusted HR, 2.65; 95% CI, 1.26, 5.55), and low-risk types (adjusted HR, 5.89; 95% CI, 1.29, 27.01). Conclusions. MSW with prior genital HPV infections had a higher risk of a subsequent type-specific anal infection. The higher risk was not explained by sexual intercourse with female partners. Autoinoculation is a possible mechanism for the observed association. PMID:27489298

Prevalence of cervical human papillomavirus infection in healthy women is related to sexual behaviours and educational level: a cross-sectional study.

PubMed

Tay, Sun Kuie; Oon, Lynette Lin Ean

2014-12-01

This study reports the prevalence and risk factors of human papillomavirus (HPV) infection in healthy women in Singapore. Demography, education, sexual and reproductive history and cigarette smoking habits were obtained from a cross-sectional population of healthy women and girls aged above 12 years of age. Cervical or vaginal cytology samples were investigated for 37 known anogenital HPV subtypes using the linear array PCR method. Chi square statistics were used to test for associations of individual epidemiological factors with HPV infection. Independent risk factors were identified with binomial logistic regression analysis. Of 891 subjects, the prevalence of HPV infection was 9.31% (83/891 women) for any-type HPV and 5.05% (46/891 women) for the high-risk HPV (hrHPV). Of 30 HPV subtypes detected, the most prevalent genotypes in descending order of frequency were subtypes 51, 16, 52, 58 and 66 for hrHPV and subtypes 62, 61, 84, 72 and 53 for the low-risk HPV. This frequency distribution of HPV subtypes was different from reports from other countries within Asia. Forty-six virgins studied tested negative for HPV infection. Significant independent risk factors for any-type HPV infection were multiple sexual partners (adjusted OR 1.4) and low (≤6 years) educational level (adjusted OR 4.0). The distribution of HPV subtypes in healthy women varies between different countries within Asia. In Singapore, the prevalence of HPV infection was 9.31% and was related to penetrative sexual intercourse, multiple sexual partners and low educational level. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Age-specific prevalence of HPV genotypes in cervical cytology samples with equivocal or low-grade lesions

PubMed Central

Brismar-Wendel, S; Froberg, M; Hjerpe, A; Andersson, S; Johansson, B

2009-01-01

Background: To define the spectrum of human papillomavirus (HPV) types and establish an age limit for triage HPV testing in atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL). Materials and methods: 343 liquid-based cytological samples from the population-based screening programme with minor abnormalities were subjected to HPV genotyping (Linear Array, Roche, Basel, Switzerland). Results: High-risk human papillomavirus (HR-HPV) was found in 71% of LSIL and 49% of ASCUS cases (P<0.001). High-risk human papillomavirus prevalence was age-dependent in LSIL (P=0.01), with decreasing prevalence until the age of 50 years, followed by a slight increase. Human papillomavirus type 16 was the most common HR-HPV, found in 23% of HPV-positive women. Human papillomavirus type 18 was the sixth most common, found in 9.9% (P<0.001). An age-dependent quadratic trend was observed for multiple infections (P=0.01) with a trough at about 42 years. The most common HR-HPV types to show a coinfection with HPV16 (clade 9) were HPV39 (28%), 45 (38%), and 59 (46%), belonging to HPV18 clade 7. The frequency of low-risk (LR) vs probable HR and HR-HPV also followed an age-dependent quadratic trend. Conclusions: After the age of 25 years, HR-HPV prevalence is similar in LSIL and ASCUS cases, motivating a low age limit for triage HPV testing. Multiple infections and LR/HR-HPV dominance are age-dependent. Genotyping in longitudinal design is needed to elucidate the importance of multiple infections in cancer progression and in cross-protection from vaccination. PMID:19623178

The 2010 Global Proficiency Study of Human Papillomavirus Genotyping in Vaccinology

PubMed Central

Eklund, Carina; Forslund, Ola; Wallin, Keng-Ling; Zhou, Tiequn

2012-01-01

Accurate and internationally comparable human papillomavirus (HPV) DNA genotyping is essential both for evaluation of HPV vaccines and for effective monitoring and implementation of vaccination programs. The World Health Organization (WHO) HPV Laboratory Network (LabNet) regularly issues international proficiency studies. The 2010 HPV genotyping proficiency panel for HPV vaccinology contained 43 coded samples composed of purified plasmids of 16 HPV types (HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68a and 68b) and 3 coded extraction controls. Proficient typing was defined as detection in both single and multiple infections of 50 international units (IU) of HPV type 16 (HPV-16) and HPV-18 DNA and 500 genome equivalents (GE) for the other 14 HPV types. Ninety-eight laboratories worldwide submitted a total of 132 data sets. Twenty-four different HPV genotyping assay methods were used, with Linear Array being the most commonly used. Other major assays used were a line blot assay (Inno-LiPa), CLART, type-specific real-time PCR, PCR Luminex, and different microarray assays. Altogether, 72 data sets were proficient for detection of more than 1 type, and only 26 data sets proficiently detected all 16 HPV types. The major oncogenic HPV types, 16 and 18, were proficiently detected in 95.0% (114/120) and 87.0% (94/108) of data sets, respectively. Forty-six data sets reported multiple false-positive results and were considered nonproficient. A trend toward increased sensitivity of assays was seen for the 41 laboratories that participated in both 2008 and 2010. In conclusion, continued global proficiency studies will be required for establishing comparable and reliable HPV genotyping services for vaccinology worldwide. PMID:22535980

Agreement for HPV genotyping detection between self-collected specimens on a FTA cartridge and clinician-collected specimens

PubMed Central

Guan, YaoYao; Gravitt, Patti E.; Howard, Roslyn; Eby, Yolanda J.; Wang, Shaoming; Li, Belinda; Feng, Changyan; Qiao, You-Lin; Castle, Philip E.

2016-01-01

The current method of transporting self-collected cervicovaginal specimen for HPV DNA testing relies on liquid based medium, which is challenging and expensive to transport. A novel, dry storage and transportation device, Whatman indicating FTA™ Elute Cartridge, avoids some of the pitfalls of liquid-based medium. This method has been shown to be comparable to liquid-based collection medium, but relative performance of self-collected (SC) and clinician-collected (CC) samples onto FTA cards has not been reported. The objective of this study is to compare the analytic performance of self- and clinician-collected samples onto FTA cartridges for the detection of carcinogenic HPV using Linear Array. There was a 91% agreement, 69% positive agreement, and kappa of 0.75 between the clinician-collected and self-collected specimens for detection of any carcinogenic HPV genotype. When the HPV results were categorized hierarchically according to cervical cancer risk, there was no difference in the distribution of the HPV results for the clinician- and self-collected specimens (p = 0.7). This study concludes that FTA elute cartridge is a promising method of specimen transport for cervical cancer screening programs considering using self-collected specimen and HPV testing. Larger studies with clinical endpoints are now needed to assess the clinical performance. PMID:23370404

Performance of the digene LQ, RH and PS HPVs genotyping systems on clinical samples and comparison with HC2 and PCR-based Linear Array.

PubMed

Godínez, Jose M; Tous, Sara; Baixeras, Nuria; Moreno-Crespi, Judith; Alejo, María; Lejeune, Marylène; Bravo, Ignacio G; Bosch, F Xavier; de Sanjosé, Silvia

2011-11-18

Certain Human Papillomaviruses (HPVs) are the infectious agents involved in cervical cancer development. Detection of HPVs DNA is part of the cervical cancer screening protocols and HPVs genotyping has been proposed for its inclusion in these preventive programs. The aim of this study was to evaluate three novel genotyping tests, namely Qiagen LQ, RH and PS, in clinical samples with and without abnormalities. For this, 305 cervical samples were processed and the results of the evaluated techniques were compared with those obtained in the HPVs diagnostic process in our lab, by using HC2 and Linear Array (LA) technologies. The concordances and kappa statistics (k) for each technique compared with HC2 were 98.69% (k = 0.94) for LQ, 98.03% (k = 0.91) for RH and 91.80% (k = 0.82) for PS. There was a very good agreement in HPVs type-specific concordance for the most prevalent types HPV16 (kappa range = 0.83-0.90), HPV18 (k.r.= 0.74-0.80) and HPV45 (k.r.= 0.82-0.90). The three tests showed an overall good concordance for HPVs detection when compared with HR-HC2 system. LQ and RH rendered lower detection rate for multiple infections than LA genotyping. However, our understanding of the clinical significance of multiple HPVs infections is still incomplete and therefore the relevance of the lower ability to detect multiple infections needs to be evaluated.

Analytic and clinical performance of cobas HPV testing in anal specimens from HIV-positive men who have sex with men.

PubMed

Wentzensen, Nicolas; Follansbee, Stephen; Borgonovo, Sylvia; Tokugawa, Diane; Sahasrabuddhe, Vikrant V; Chen, Jie; Lorey, Thomas S; Gage, Julia C; Fetterman, Barbara; Boyle, Sean; Sadorra, Mark; Tang, Scott Dahai; Darragh, Teresa M; Castle, Philip E

2014-08-01

Anal human papillomavirus (HPV) infections are common, and the incidence of anal cancer is high in HIV-infected men who have sex with men (MSM). To evaluate the performance of HPV assays in anal samples, we compared the cobas HPV test (cobas) to the Roche Linear Array HPV genotyping assay (LA) and cytology in HIV-infected MSM. Cytology and cobas and LA HPV testing were conducted for 342 subjects. We calculated agreement between the HPV assays and the clinical performance of HPV testing and HPV genotyping alone and in combination with anal cytology. We observed high agreement between cobas and LA, with cobas more likely than LA to show positive results for HPV16, HPV18, and other carcinogenic types. Specimens testing positive in cobas but not in LA were more likely to be positive for other markers of HPV-related disease compared to those testing negative in both assays, suggesting that at least some of these were true positives for HPV. cobas and LA showed high sensitivities but low specificities for the detection of anal intraepithelial neoplasia grade 2/3 (AIN2/3) in this population (100% sensitivity and 26% specificity for cobas versus 98.4% sensitivity and 28.9% specificity for LA). A combination of anal cytology and HPV genotyping provided the highest accuracy for detecting anal precancer. A higher HPV load was associated with a higher risk of AIN2/3 with HPV16 (P(trend) < 0.001), HPV18 (P(trend) = 0.07), and other carcinogenic types (P(trend) < 0.001). We demonstrate that cobas can be used for HPV detection in anal cytology specimens. Additional tests are necessary to identify men at the highest risk of anal cancer among those infected with high-risk HPV. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Impact of human immunodeficiency virus on the natural history of human papillomavirus genital infection in South African men and women.

PubMed

Mbulawa, Zizipho Z A; Marais, Dianne J; Johnson, Leigh F; Coetzee, David; Williamson, Anna-Lise

2012-07-01

This study investigated genital human papillomavirus (HPV) incidence and clearance in 278 human immunodeficiency virus (HIV)-seropositive (HIV-positive) women, 208 HIV-negative women, 161 HIV-positive men, and 325 HIV-negative men, followed at 6-month intervals for up to 24 months. HPV types were determined by the Roche Reverse Linear Array HPV genotyping assay. The rate of new HPV detection at the cervix and penis were 33.83 events/1000 person-months (95% confidence interval [CI], 26.39-43.46) and 55.68 events/1000 person-months (95% CI, 43.59-69.19), respectively. HIV infection was associated with increased risk of new HPV detection in women (relative risk [RR], 2.98; 95% CI, 2.07-4.29) and men (RR, 2.00; 95% CI, 1.49-2.69). The risk of new HPV detection increased in women (RR, 5.25; 95% CI, 3.52-7.81) and men (RR, 8.71; 95% CI, 6.19-12.24) when the sexual partner was infected with the same HPV type. The rate of clearing any HPV infection was 95.1 events/1000 person-months (95% CI, 83.3-108.1) in men and 66.9 events/1000 person-months (95% CI, 57.0-78.5) in women. HIV infection reduced the rate of HPV clearance in women (RR, 0.46; 95% CI, .34-.62) and men (RR, 0.71; 95% CI, .55-.93). HIV infection increases the risk of new HPV detection and decreases the rate of HPV clearance in both women and men.

Sequential Acquisition of Anal Human Papillomavirus (HPV) Infection Following Genital Infection Among Men Who Have Sex With Women: The HPV Infection in Men (HIM) Study.

PubMed

Pamnani, Shitaldas J; Nyitray, Alan G; Abrahamsen, Martha; Rollison, Dana E; Villa, Luisa L; Lazcano-Ponce, Eduardo; Huang, Yangxin; Borenstein, Amy; Giuliano, Anna R

2016-10-15

The purpose of this study was to assess the risk of sequential acquisition of anal human papillomavirus (HPV) infection following a type-specific genital HPV infection for the 9-valent vaccine HPV types and investigate factors associated with sequential infection among men who have sex with women (MSW). Genital and anal specimens were available for 1348 MSW participants, and HPV genotypes were detected using the Roche Linear Array assay. Sequential risk of anal HPV infection was assessed using hazard ratios (HRs) among men with prior genital infection, compared with men with no prior genital infection, in individual HPV type and grouped HPV analyses. In individual analyses, men with prior HPV 16 genital infections had a significantly higher risk of subsequent anal HPV 16 infections (HR, 4.63; 95% confidence interval [CI], 1.41-15.23). In grouped analyses, a significantly higher risk of sequential type-specific anal HPV infections was observed for any of the 9 types (adjusted HR, 2.80; 95% CI, 1.32-5.99), high-risk types (adjusted HR, 2.65; 95% CI, 1.26, 5.55), and low-risk types (adjusted HR, 5.89; 95% CI, 1.29, 27.01). MSW with prior genital HPV infections had a higher risk of a subsequent type-specific anal infection. The higher risk was not explained by sexual intercourse with female partners. Autoinoculation is a possible mechanism for the observed association. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Risk factors for infection by oncogenic human papillomaviruses in HIV-positive MSM patients in the ART era (2010-2016).

PubMed

Hidalgo-Tenorio, Carmen; Gil-Anguita, Concepción; Ramírez-Taboada, Jessica; Esquivias, Javier; López-Ruz, Miguel A; Balgahata, Omar Mohamed; Javier-Martinez, Rosario; Pasquau, Juan

2017-09-01

Squamous cell carcinoma of anus (SCCA) is one of the most frequent non-AIDS-defining diseases in HIV patients, mainly in men who have sex with men (MSM), and it is associated with human papillomavirus (HPV) infection.To determine the prevalence of high-risk HPV (HR-HPV) genotypes, premalignant lesions (HSIL) and SCCA in a cohort of HIV-positive MSM; to study the distribution of HPV genotypes according to anal histology results; and to analyze risk factors for this infection.This prospective single-center study was conducted between May 2010 and September 2016. At the study visit, cotton swabs were used to collect anal samples for cytology study in ThinPrep Pap Test liquid medium (Thin Prep Processor 2000, Hologic Corp, USA), and for HPV PCR (Linear Array HPV Genotyping Test). After, high-resolution anoscopy (HRA) (Zeiss 150 fc) was carried out. Logistic regression analysis was performed to identify risk factors for HR-HPV infection.The study included 319 patients, with mean age of 36.7 years; HR-HPV was detected in 81.3%. The prevalence of HSIL was 13.5% and SCCA was 0.3%. With regard to the distribution of HPV genotypes according to histology results, HPV 16 was the most frequent genotype in normal anal mucosa (26.7%), in LSILs (36.9%), and in HSILs (38%). In multivariate analysis, CD4 nadir < 200 cells/μL was the factor associated with infection by HR-HPV (OR 3.66, 95% CI 1.05%-12.75%).HIV-positive MSM showed a high prevalence of HSIL+ lesions and of infection by oncogenic HPV, which appears to be favored by a deficient immune system. HPV 16 was the most frequently isolated genotype in anal mucosa, regardless of lesion type.

Prevalence of high-risk human papilloma virus genotypes and associated risk of cervical precancerous lesions in a large U.S. screening population: data from the ATHENA trial.

PubMed

Monsonego, Joseph; Cox, J Thomas; Behrens, Catherine; Sandri, Maria; Franco, Eduardo L; Yap, Poh-Sin; Huh, Warner

2015-04-01

We assessed the age-related prevalence of high risk human papillomavirus (HR-HPV) genotypes and the genotype-associated risk for high-grade cervical intraepithelial neoplasia (CIN) in a large U.S. screening population. A total of 40,901 women aged ≥25 years were screened with liquid-based cytology and HPV testing in the ATHENA (Addressing the Need for Advanced HPV Diagnostics) trial. Genotyping was performed using the LINEAR ARRAY HPV Genotyping Test. HPV16 was the most prevalent genotype in all age groups, ranging from 3.5% to 0.8% in women aged 25-29 and ≥50 years, respectively. The next most prevalent genotypes were HPV52, HPV31 and HPV18. In the overall population, HPV16 conferred the greatest absolute risk of ≥CIN3 both in women aged 25-29 and ≥30 years (14.2% and 15.1%, respectively) followed by HPV31 (8.0% and 7.9%), HPV52 (6.7% and 4.4%) and HPV18 (2.7% and 9.0%). Similar trends were seen in women with negative cytology. The percent positivity increased markedly with disease progression for HPV16 and HPV18 which were responsible for 45.6% and 8.4% of ≥CIN3, respectively. Of note, HPV 18 was responsible for 50% of adenocarcinoma in situ (AIS) and 50% of invasive cancer cases. HPV16 played a major role in the development of ≥CIN3 irrespective of age, supporting the identification of HPV16 in primary screening for all women. Identification of HPV18 is also warranted, given its significant contribution to AIS and cancer. Identification of non-16/18 genotypes as a pool should provide sufficient information for screening. Copyright © 2015. Published by Elsevier Inc.

Genital Human Papillomavirus Infection Progression to External Genital Lesions: The HIM Study.

PubMed

Sudenga, Staci L; Ingles, Donna J; Pierce Campbell, Christine M; Lin, Hui-Yi; Fulp, William J; Messina, Jane L; Stoler, Mark H; Abrahamsen, Martha; Villa, Luisa L; Lazcano-Ponce, Eduardo; Giuliano, Anna R

2016-01-01

Human papillomavirus (HPV) causes two types of external genital lesions (EGLs) in men: genital warts (condyloma) and penile intraepithelial neoplasia (PeIN). The purpose of this study was to describe genital HPV progression to a histopathologically confirmed HPV-related EGL. A prospective analysis nested within the HPV Infection in Men (HIM) study was conducted among 3033 men. At each visit, visually distinct EGLs were biopsied; the biopsy specimens were subjected to pathologic evaluation and categorized by pathologic diagnoses. Genital swabs and biopsies were used to identify HPV types using the Linear Array genotyping method for swabs and INNO-LiPA for biopsy specimens. EGL incidence was determined among 1788 HPV-positive men, and cumulative incidence rates at 6, 12, and 24 mo were estimated. The proportion of HPV infections that progressed to EGL was also calculated, along with median time to EGL development. Among 1788 HPV-positive men, 92 developed an incident EGL during follow-up (9 PeIN and 86 condyloma). During the first 12 mo of follow-up, 16% of men with a genital HPV 6 infection developed an HPV 6-positive condyloma, and 22% of genital HPV 11 infections progressed to an HPV 11-positive condyloma. During the first 12 mo of follow-up, 0.5% of men with a genital HPV 16 infection developed an HPV 16-positive PeIN. Although we expected PeIN to be a rare event, the sample size for PeIN (n=10) limited the types of analyses that could be performed. Most EGLs develop following infection with HPV 6, 11, or 16, all of which could be prevented with the 4-valent HPV vaccine. In this study, we looked at genital human papillomavirus (HPV) infections that can cause lesions in men. The HPV that we detected within the lesions could be prevented by a vaccine. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Assessing genital human papillomavirus genoprevalence in young Australian women following the introduction of a national vaccination program.

PubMed

Osborne, Sarah L; Tabrizi, Sepehr N; Brotherton, Julia M L; Cornall, Alyssa M; Wark, John D; Wrede, C David; Jayasinghe, Yasmin; Gertig, Dorota M; Pitts, Marian K; Garland, Suzanne M

2015-01-01

Following the implementation of Australia's National HPV Vaccination Program in April 2007, this study evaluated the prevalence of vaccine-targeted human papillomavirus (HPV) genotypes (HPV 6, 11, 16, 18) amongst vaccine-eligible young women. Between September 2011 and August 2013, women from Victoria, Australia aged 18-25 were recruited through targeted advertising on the social networking website Facebook. Participants completed an online questionnaire, and sexually active women were asked to provide a self-collected vaginal swab for HPV deoxyribonucleic acid (DNA) detection and genotyping. Samples positive for HPV were genotyped using the Linear Array HPV genotyping test (Roche Diagnostics). Self-reported HPV vaccination details were verified with the National HPV Vaccination Program Register (NHVPR). Of 431 vaginal swabs, 24.8% were positive for HPV DNA. Vaccine-targeted HPV genotypes were detected in only seven (1.6%) samples; all HPV 16 (of the six HPV 16 positive vaccinated women, all had received the vaccine after sexual debut). There were no cases of HPV 6, 11 or 18 identified. HPV types 51, 59, 73, 84, and 89 were the most prevalent genotypes. Vaccination rates were high, with 77.3% of participants having received all three doses of the vaccine, and there was an 89.8% concordance between self-reported and registry-reported HPV vaccination status. Strong associations were observed between vaccination status, age, language spoken at home and country of birth, as well as between HPV detection and the number of male sexual partners. Preliminary data from this study demonstrate a very low prevalence of vaccine-related HPV genotypes amongst vaccine-eligible women from Victoria, Australia. We were able to use Facebook to effectively reach and recruit young women to participate in the assessment of the impact of Australia's HPV vaccination program. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Genotyping of oncogenic human papilloma viruses in women with HG SIL diagnosis].

PubMed

Kedzia, Witold; Pruski, Dominik; Józefiak, Agata; Rokita, Wojciech; Spaczyński, Marek

2010-10-01

Development of primary prevention of cervical cancer in other words a vaccination against selected, oncogenic HPV types, entails an increasing importance of epidemiological studies and prevalence of various types of human papilloma virus. The incidence of HPV varies depending on the geographic location of the population. The effectiveness of primary prevention against HPV 16, 18, in the context of reducing the incidence of cervical cancer will depend, among others, on the prevalence of these types in the population and virus-like antigens, which are partially cross-resistant. Identification of the most frequent, oncogenic HPV types in women with HG SIL diagnosis from Central and Western Poland to assess the merits of the development of primary prevention. For the purpose of molecular tests identifying the presence of 13 DNA oncogenic virus types, swabs were taken with the cyto-brush from 76 women diagnosed with CIN 2 or CIN 3 (HG SIL). Patients eligible for the study were diagnosed at the Laboratory of Pathophysiology of Uterine Cervix, Gynecology and Obstetrics Clinical Hospital of Karol Marcinkowski University of Medical Sciences. Patients came from Central and Western parts of Poland. Cell material in which the method of Amplicor HPV (Roche Diagnostics) identified the presence of DNA of oncogenic HPV types was in each case subsequently subjected to genotyping using the molecular test - Linear Array HPV Genotyping (Roche Diagnostics). Five most common oncogenic HPV types in order of detection included: 16, 33, 18, 31, 56. Together these five types of virus comprised 75.86% (88/116) of all detected HPV types. 1. In women from Central and Western Poland, diagnosed with HG SIL, the most common HPV genotypes were HPV 16, HPV33, HPV 18, HPV31, HPV56. 2. Two HPV types 16 and 18, against which vaccinations are directed, belong to the group of three genotypes of HPV most commonly identified in the evolution of CIN 2, CIN 3 diagnosed in women from Central and Western Poland.

Evaluation of a Novel Single-Tube Method for Extended Genotyping of Human Papillomavirus

PubMed Central

Serrano, I.; Wennington, H.; Graham, C.; Cubie, H.; Boland, E.; Fu, G.; Cuschieri, K.

2017-01-01

ABSTRACT The use of high-risk human papillomavirus (HPV) testing for surveillance and clinical applications is increasing globally, and it is important that tests are evaluated to ensure they are fit for this purpose. In this study, the performance of a new HPV genotyping test, the Papilloplex high-risk HPV (HR-HPV) test, was compared to two well-established genotyping tests. Preliminary clinical performance was also ascertained for the detection of CIN2+ in a disease-enriched retrospective cohort. A panel of 500 cervical liquid-based cytology samples with known clinical outcomes were tested by the Papilloplex HR-HPV test. Analytical concordance was compared to two assays: a Linear Array (LA) HPV genotyping test and an Optiplex HPV genotyping test. The initial clinical performance for the detection for CIN2+ samples was performed and compared to that of two clinically validated HPV tests: a RealTime High-Risk HPV test (RealTime) and a Hybrid Capture 2 HPV test (HC2). High agreement for HR-HPV was observed between the Papilloplex and LA and Optiplex HPV tests (97 and 95%, respectively), with kappa values for HPV16 and HPV18 being 0.90 and 0.81 compared to the LA and 0.70 and 0.82 compared to the Optiplex test. The sensitivity, specificity, positive predictive value, and negative predictive value of the Papilloplex test for the detection of CIN2+ were 92, 54, 33, and 96%, respectively, and very similar to the values observed with RealTime and HC2. The Papilloplex HR-HPV test demonstrated a analytical performance similar to those of the two HPV genotyping tests at the HR-HPV level and the type-specific level. The preliminary data on clinical performance look encouraging, although further longitudinal studies within screening populations are required to confirm these findings. PMID:29237790

HPV genotypes in high grade cervical lesions and invasive cervical carcinoma as detected by two commercial DNA assays, North Carolina, 2001-2006.

PubMed

Hariri, Susan; Steinau, Martin; Rinas, Allen; Gargano, Julia W; Ludema, Christina; Unger, Elizabeth R; Carter, Alicia L; Grant, Kathy L; Bamberg, Melanie; McDermott, James E; Markowitz, Lauri E; Brewer, Noel T; Smith, Jennifer S

2012-01-01

HPV typing using formalin fixed paraffin embedded (FFPE) cervical tissue is used to evaluate HPV vaccine impact, but DNA yield and quality in FFPE specimens can negatively affect test results. This study aimed to evaluate 2 commercial assays for HPV detection and typing using FFPE cervical specimens. Four large North Carolina pathology laboratories provided FFPE specimens from 299 women ages18 and older diagnosed with cervical disease from 2001 to 2006. For each woman, one diagnostic block was selected and unstained serial sections were prepared for DNA typing. Extracts from samples with residual lesion were used to detect and type HPV using parallel and serial testing algorithms with the Linear Array and LiPA HPV genotyping assays. LA and LiPA concordance was 0.61 for detecting any high-risk (HR) and 0.20 for detecting any low-risk (LR) types, with significant differences in marginal proportions for HPV16, 51, 52, and any HR types. Discordant results were most often LiPA-positive, LA-negative. The parallel algorithm yielded the highest prevalence of any HPV type (95.7%). HR type prevalence was similar using parallel (93.1%) and serial (92.1%) approaches. HPV16, 33, and 52 prevalence was slightly lower using the serial algorithm, but the median number of HR types per woman (1) did not differ by algorithm. Using the serial algorithm, HPV DNA was detected in >85% of invasive and >95% of pre-invasive lesions. The most common type was HPV16, followed by 52, 18, 31, 33, and 35; HPV16/18 was detected in 56.5% of specimens. Multiple HPV types were more common in lower grade lesions. We developed an efficient algorithm for testing and reporting results of two commercial assays for HPV detection and typing in FFPE specimens, and describe HPV type distribution in pre-invasive and invasive cervical lesions in a state-based sample prior to HPV vaccine introduction.

[Prevalence of human papilloma virus isolated from cervix lesions in a female population from Transilvania].

PubMed

Feticu, Lucia; Bocşan, I S; Bondor, Cosmina loana; Boboş, Cecilia

2012-01-01

Between the years 2008-2011 reverse hibridisation (INNO-LiPA HPV Genotyping Extra test) and genotyping 1a Roche (the kit: Linear array HPV genotyping test) were used for detection of Human Papilloma Virus (HPV) in the cervix secretions of 182 female patients aged 16-63 years, predominantly of urban origin. 99 patients (54.4%) were identified as being infected with various types of HPV, prevalent in urban (53 single infections and 46 multiple infections). HPV infection was not detected in 83 (45.6%) patients. Only 7 females from rural areas were tested (5 females had single or multiple HPV infections). 32 types of HPV were identificated: 15 HPV types with high risk (51, 82, 56, 18, 39, 45, 59, 68, 16, 31, 33, 35, 52, 58, 73), 14 types with low risk (42, 61, 62, 72, 81, 83, 84, CP6108, 70, 6, 11, 55, 74, 54), and 3 types with possible high risk (26, 53, 66). The type of HPV could not be identified in other two cases. The most frecvent types of HPV with high risk isolated were: the type 16. The types 51 and 58 of HPV with high risk and the type 84 with low risk are detected in single infections in urban and in rural. HPV clades involved in single infections are: 1 (1 case), 3 (5 cases), 5 (4 cases), 6 (5 cases), 7 (5 cases), 9 (21 cases), 10 (7 cases). The clades 11 (7 cases) and 13 (6 cases) were involved only in multiple infections detected in urban. The types 35, 39, 59, 68 of HPV with high risk were isolated from multple infections. In rural, multiple infections with two HPV were detected. The citological screening by Babe-Papanicolaou examination was made only in 9 cases: HPV was not detected in 4 cases (one female had ASC-US: atypical squamous cells of "undetermined significance"); in 5 positive cases were detected HPV 16, 31, 58, 6.

HPV prevalence and type-distribution in cervical cancer and premalignant lesions of the cervix: A population-based study from Northern Ireland.

PubMed

Anderson, Lesley A; O'Rorke, Michael A; Wilson, Robbie; Jamison, Jackie; Gavin, Anna T

2016-07-01

Assessment of Human papillomavirus (HPV) prevalence and genotype distribution is important for monitoring the impact of prophylactic HPV vaccination. This study aimed to demonstrate the HPV genotypes predominating in pre-malignant and cervical cancers in Northern Ireland (NI) before the vaccination campaign has effect. Formalin fixed paraffin embedded tissue blocks from 2,303 women aged 16-93 years throughout NI were collated between April 2011 and February 2013. HPV DNA was amplified by PCR and HPV genotyping undertaken using the Roche(®) linear array detection kit. In total, 1,241 out of 1,830 eligible samples (68.0%) tested positive for HPV, with the majority of these [1,181/1,830 (64.5%)] having high-risk (HR) HPV infection; 37.4% were positive for HPV-16 (n = 684) and 5.1% for HPV-18 (n = 93). HPV type-specific prevalence was 48.1%, 65.9%, 81.3%, 92.2%, and 64.3% among cervical intraepithelial neoplasias (CIN) Grades I-III, squamous cell carcinomas (SCC) and adenocarcinoma (AC) cases, respectively. Most SCC cases (81.3%) had only one HPV genotype detected and almost a third (32.0%) of all cervical pathologies were HPV negative including 51.9% of CIN I (n = 283), 34.1% CIN II (n = 145), 18.7% of CIN III (n = 146), 7.8% of SCC (n = 5), and 35.7% of AC (n = 5) cases. This study provides important baseline data for monitoring the effect of HPV vaccination in NI and for comparison with other UK regions. The coverage of other HR-HPV genotypes apart from 16 and 18, including HPV-45, 31, 39, and 52, and the potential for cross protection, should be considered when considering future polyvalent vaccines. © 2015 Wiley Periodicals, Inc.

Six years genotype distribution of Human Papillomavirus in Calabria Region, Southern Italy: a retrospective study.

PubMed

Galati, Luisa; Peronace, Cinzia; Fiorillo, Maria Teresa; Masciari, Rosanna; Giraldi, Cristina; Nisticò, Salvatore; Minchella, Pasquale; Maiolo, Vincenzo; Barreca, Giorgio Settimo; Marascio, Nadia; Lamberti, Angelo Giuseppe; Giancotti, Aida; Lepore, Maria Gabriella; Greco, Francesca; Mauro, Maria Vittoria; Borelli, Annelisa; Bocchiaro, Giuseppa Lo; Surace, Giovanni; Liberto, Maria Carla; Focà, Alfredo

2017-01-01

Although analysis of the Human papillomavirus (HPV) genotype spread in a particular area has a crucial impact on public health and prevention programmes, there is a lack of epidemiological data regarding HPV in the Calabria region of Italy. We therefore update information on HPV age/genotype distribution by retrospectively analysing a cohort of women, with and without cervical lesions, living in Calabria, who underwent HPV DNA testing; moreover, we also evaluated HPV age/genotype distribution in a subset of patients with cervical lesions. Cervical scrape specimens obtained from 9590 women (age range 20-75 years) from January 2010 to December 2015 were tested for HPV DNA. Viral types were genotyped by Linear Array HPV Genotyping® test (Roche, USA) at the Clinical Microbiology Operative Unit of six hospitals located in four provinces of the Calabria region. Cervical scrape specimens were also used to perform Pap smears for cytological analysis in a subset of 405 women; cytological classification of the samples was performed according to the Bethesda classification system. A total of 2974 women (31%) (C.I. 95% 30.09-31.94) were found to be HPV DNA positive for at least one (57.3%) or several (42.7%) HPV genotypes. Of single genotype HPV infections, 46.5% and 36.4 % were classed as high-risk (HR, Group 1) and low-risk (LR, Group 3) respectively, while 16.9% were classed as probably/possibly carcinogenic and 0.2% undetermined risk. Stratified by age, total HPV distribution, showed the highest prevalence within the range 30-39 years (37.2%), while single genotype infection distribution displayed a peak in women from the age range 20-29 years (37.5%). The most common high-risk HPV type was HPV 16 (19.1%), followed by HPV 31 (9.1%). We provide epidemiological data on HPV age/genotype distribution in women living in the Calabria region with or without cytological abnormalities, further to the enhancement of HPV screening/prevention programmes for the local population.

Agreement for HPV genotyping detection between self-collected specimens on a FTA cartridge and clinician-collected specimens.

PubMed

Guan, Yaoyao; Gravitt, Patti E; Howard, Roslyn; Eby, Yolanda J; Wang, Shaoming; Li, Belinda; Feng, Changyan; Qiao, You-Lin; Castle, Philip E

2013-04-01

The current method of transporting self-collected cervicovaginal specimen for HPV DNA testing relies on liquid based medium, which is challenging and expensive to transport. A novel, dry storage and transportation device, Whatman indicating FTA™ Elute Cartridge, avoids some of the pitfalls of liquid-based medium. This method has been shown to be comparable to liquid-based collection medium, but relative performance of self-collected (SC) and clinician-collected (CC) samples onto FTA cards has not been reported. The objective of this study is to compare the analytic performance of self- and clinician-collected samples onto FTA cartridges for the detection of carcinogenic HPV using Linear Array. There was a 91% agreement, 69% positive agreement, and kappa of 0.75 between the clinician-collected and self-collected specimens for detection of any carcinogenic HPV genotype. When the HPV results were categorized hierarchically according to cervical cancer risk, there was no difference in the distribution of the HPV results for the clinician- and self-collected specimens (p=0.7). This study concludes that FTA elute cartridge is a promising method of specimen transport for cervical cancer screening programs considering using self-collected specimen and HPV testing. Larger studies with clinical endpoints are now needed to assess the clinical performance. Copyright © 2012 Elsevier B.V. All rights reserved.

Utility of the Roche Cobas 4800 for detection of high-risk human papillomavirus in formalin-fixed paraffin-embedded oropharyngeal squamous cell carcinoma.

PubMed

Pettus, Jason R; Wilson, Terri L; Steinmetz, Heather B; Lefferts, Joel A; Tafe, Laura J

2017-02-01

Clinical laboratories are expected to reliably identify human papilloma virus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) for prognostic and potential therapeutic applications. In addition to surrogate p16 immunohistochemistry (IHC) testing, DNA-based HPV-specific testing strategies are widely utilized. Recognizing the efficiency of the Roche Cobas 4800 platform for testing gynecological cytology specimens for high-risk HPV, we elected to evaluate the potential utility of this platform for testing formalin-fixed paraffin-embedded (FFPE) OPSCC tissue. Using the Roche Linear Array assay for comparison, we tested twenty-eight samples (16 primary OPSCC, 2 lymph node metastases from primary OPSCC, 1 oral tongue carcinoma, 3 benign squamous papillomas, and 3 non-oropharyngeal carcinoma tissues). Excluding two invalid results, the Roche Cobas 4800 testing resulted in excellent inter-assay concordance (25/26, 96.2%) and 100% concordance for HPV-16/HPV-18 positive samples. This data suggests that the Roche Cobas 4800 platform may be a cost-effective method for testing OPSCC FFPE tissues in a clinical molecular pathology laboratory setting. Copyright © 2016 Elsevier Inc. All rights reserved.

Concordance of human papillomavirus types detected on the surface and in the tissue of genital lesions in men.

PubMed

Anic, Gabriella M; Messina, Jane L; Stoler, Mark H; Rollison, Dana E; Stockwell, Heather; Villa, Luisa L; Lazcano-Ponce, Eduardo; Gage, Christine; Silva, Roberto Jose C; Baggio, Maria L; Salmerón, Jorge; Giuliano, Anna R

2013-09-01

Swabbing the surface of a genital lesion to obtain a sample for HPV DNA testing is less invasive than a biopsy, but may not represent HPV types present in the lesion tissue. The objective of this study was to examine the concordance of HPV types detected in swab and biopsy samples from 165 genital lesions from men ages 18-70. Lesions included 90 condyloma, 10 penile intraepithelial neoplasia (PeIN), 23 non-condyloma with a known histology, and 42 lesions with an undetermined histology. All lesions were sampled by swabbing the surface of the lesion with a pre-wetted Dacron swab and taking a shave biopsy. HPV genotyping was performed using Linear Array for swab samples and INNO-LiPA for biopsy samples. The kappa and McNemar statistics were used to compare the concordance of detecting HPV types in swab and biopsy samples. Both sampling methods had high agreement for detection of HPV DNA in condyloma (87.8% agreement) and PeIN (100% agreement). There was also high concordance for detection of HPV16 (kappa = 1.00) and HPV18 (kappa = 1.00) in PeIN, however, agreement was low to moderate for detecting HPV6 (kappa = 0.31) and HPV11 (kappa = 0.56) in condyloma. Low to moderate agreement was also observed between sampling methods for detecting individual HPV types in the non-condyloma and lesions with an indefinite histology. The results suggest that obtaining a biopsy in addition to swabbing the surface of a lesion may provide additional information about specific HVP types associated with male genital lesions. Copyright © 2013 Wiley Periodicals, Inc.

The Role of Human Papillomavirus Genotyping in Cervical Cancer Screening: A Large-Scale Evaluation of the cobas HPV Test.

PubMed

Schiffman, Mark; Boyle, Sean; Raine-Bennett, Tina; Katki, Hormuzd A; Gage, Julia C; Wentzensen, Nicolas; Kornegay, Janet R; Apple, Raymond; Aldrich, Carrie; Erlich, Henry A; Tam, Thanh; Befano, Brian; Burk, Robert D; Castle, Philip E

2015-09-01

The cobas HPV Test ("cobas"; Roche Molecular Systems) detects HPV16 and HPV18 individually, and a pool of 12 other high-risk (HR) HPV types. The test is approved for (i) atypical squamous cells of undetermined significance (ASC-US) triage to determine need for colposcopy, (ii) combined screening with cytology ("cotesting"), and (iii) primary HPV screening. To assess the possible value of HPV16/18 typing, >17,000 specimens from a longitudinal cohort study of initially HPV-positive women (HC2, Qiagen) were retested with cobas. To study accuracy, cobas genotyping results were compared with those of an established method, the Linear Array HPV Genotyping Test (LA, Roche Molecular Systems). Clinical value of the typing strategy was evaluated by linking the cobas results (supplemented by other available typing results) to 3-year cumulative risks of CIN3+. Grouped hierarchically (HPV16, else HPV18, else other HR types, else negative), the κ statistic for agreement between cobas and LA was 0.86 [95% confidence interval (CI), 0.86-0.87]. In all three scenarios, HPV16-positive women were at much higher 3-year risk of CIN3+ than HPV16-negative women: women ages 21 and older with ASC-US (14.5%; 95% CI, 13.5%-15.5% vs. 3.5%; 95% CI, 3.3-3.6); women ages 30 years and older that were HPV-positive cytology-negative (10.3%; 95% CI, 9.6-11.1 vs. 2.3%; 95% CI, 2.2-2.4); and all women 25 years and older that were HPV-positive (18.5%; 95% CI, 17.8-19.2 vs. 4.3%; 95% CI, 4.2-4.4). The cobas and LA results show excellent agreement. The data support HPV16 typing. HPV16 typing is useful in the management of HPV-positive/cytology-negative women in cotesting, of all HPV-positive women in primary HPV testing, and perhaps in the management of HPV-positive women with ASC-US. Cancer Epidemiol Biomarkers Prev; 24(9); 1304-10. ©2015 American Association for Cancer Research.

Final analysis of a study assessing genital human papillomavirus genoprevalence in young Australian women, following eight years of a national vaccination program.

PubMed

Garland, Suzanne M; Cornall, Alyssa M; Brotherton, Julia M L; Wark, John D; Malloy, Michael J; Tabrizi, Sepehr N

2018-05-31

The VACCINE [Vaccine Against Cervical Cancer Impact and Effectiveness] study evaluated the prevalence of quadrivalent vaccine-targeted human papillomavirus (HPV) genotypes (HPV 6, 11, 16, 18) amongst young women of vaccine-eligible age. Between October 2011 - June 2015, women aged 18-25 years from Victoria, Australia, were recruited through targeted advertising on the social networking website Facebook. Participants completed an online questionnaire and provided a self-collected vaginal swab for HPV DNA detection and genotyping (Linear Array HPV genotyping assay). Self-reported HPV vaccination details were verified with the National HPV Vaccination Program Register (NHVPR). Of 1223 who agreed to participate, 916 (74.9%) completed the survey and, for 1007 (82.3%) sexually-active participants, 744 (73.9%) returned the self-collected swab, of which 737 contained detectable DNA. 184/737 (25.0%) were positive for HPV. Vaccine-targeted HPV genotypes were detected in only 13 (1.7%) women: 11 HPV 16 (six vaccinated after sexual debut, five unvaccinated) and two HPV 6. Prevalence of any of HPV 31/33/45 collectively was 2.9%, varying significantly by vaccination status (fully 2.0%, unvaccinated 6.8%; p = 0.01). Vaccination rates among the sexually-active cohort were high, with 65.6%, 71.6% and 74.2% of participants having received three, at least two or at least one dose of vaccine, respectively. Of women self-reporting HPV vaccination, the NHVPR confirmed one or more doses were received in 90%. Strong associations were observed between vaccination status, age, language spoken at home and country of birth, as well as between HPV detection and the number of male sexual partners. Surveillance five to eight years' post-initiation of a national HPV vaccination program demonstrated a consistent and very low prevalence of vaccine-related HPV genotypes and some evidence of cross protection against related types amongst vaccine-eligible women from Victoria, Australia. Copyright © 2018. Published by Elsevier Ltd.

Prevalence and correlates of oral human papillomavirus infection among healthy males and females in Lima, Peru.

PubMed

Rosen, Brian J; Walter, Leora; Gilman, Robert H; Cabrerra, Lilia; Gravitt, Patti E; Marks, Morgan A

2016-03-01

The incidence of human papillomavirus (HPV) associated head and neck cancers (HNCs) have been increasing in Peru. However, the burden of oral HPV infection in Peru has not been assessed. The objective of this cross-sectional study was to estimate the prevalence and correlates of oral HPV infection in a population-based sample from males and females from Lima, Peru. Between January 2010 and June 2011, a population-based sample of 1099 individuals between the ages of 10 and 85 from a low-income neighbourhood in Lima, Peru was identified through random household sampling. Information on demographic, sexual behaviours, reproductive factors and oral hygiene were collected using interviewer-administered questionnaires. Oral rinse specimens were collected from each participant, and these specimens were genotyped using the Roche Linear Array assay. ORs were used to assess differences in the prevalence of any oral HPV and any high-risk oral HPV infection by demographic factors, sexual practices and oral hygiene among individuals 15+ years of age. The prevalence of any HPV and any high-risk HPV (HR-HPV) was 6.8% and 2.0%, respectively. The three most common types were HPV 55 (3.4%), HPV 6 (1.5%) and HPV 16 (1.1%). Male sex (aOR, 2.21; 95% CI 1.22 to 4.03) was associated with any HPV infection after adjustment. The prevalence of oral HPV in this study was similar to estimates observed in the USA. Higher prevalence of oral infections in males was consistent with a male predominance of HPV-associated HNCs and may signal a sex-specific aetiology in the natural history of infection. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Genotyping for Human Papillomavirus (HPV) 16/18/52/58 Has a Higher Performance than HPV16/18 Genotyping in Triaging Women with Positive High-risk HPV Test in Northern Thailand

PubMed Central

Khunamornpong, Surapan; Settakorn, Jongkolnee; Sukpan, Kornkanok; Suprasert, Prapaporn; Srisomboon, Jatupol; Intaraphet, Suthida; Siriaunkgul, Sumalee

2016-01-01

Background Testing for high-risk human papillomavirus DNA (HPV test) has gained increasing acceptance as an alternative method to cytology in cervical cancer screening. Compared to cytology, HPV test has a higher sensitivity for the detection of histologic high-grade squamous intraepithelial lesion or worse (HSIL+), but this could lead to a large colposcopy burden. Genotyping for HPV16/18 has been recommended in triaging HPV-positive women. This study was aimed to evaluate the screening performance of HPV testing and the role of genotyping triage in Northern Thailand. Methods A population-based cervical screening program was performed in Chiang Mai (Northern Thailand) using cytology (conventional Pap test) and HPV test (Hybrid Capture 2). Women who had abnormal cytology or were HPV-positive were referred for colposcopy. Cervical samples from these women were genotyped using the Linear Array assay. Results Of 5,456 women, 2.0% had abnormal Pap test results and 6.5% tested positive with Hybrid Capture 2. Of 5,433 women eligible for analysis, 355 with any positive test had histologic confirmation and 57 of these had histologic HSIL+. The sensitivity for histologic HSIL+ detection was 64.9% for Pap test and 100% for Hybrid Capture 2, but the ratio of colposcopy per detection of each HSIL+ was more than two-fold higher with Hybrid Capture 2 than Pap test (5.9 versus 2.8). Genotyping results were available in 316 samples. HPV52, HPV16, and HPV58 were the three most common genotypes among women with histologic HSIL+. Performance of genotyping triage using HPV16/18/52/58 was superior to that of HPV16/18, with a higher sensitivity (85.7% versus 28.6%) and negative predictive value (94.2% versus 83.9%). Conclusions In Northern Thailand, HPV testing with genotyping triage shows better screening performance than cervical cytology alone. In this region, the addition of genotyping for HPV52/58 to HPV16/18 is deemed necessary in triaging women with positive HPV test. PMID:27336913

Human papillomavirus genotypes and clinical management of genital warts in women attending a colposcopy clinic in Cape Town, South Africa.

PubMed

Tayib, Shahila; Allan, Bruce; Williamson, Anna-Lise; Denny, Lynette

2015-09-21

Genital human papillomavirus (HPV) infection is the most common sexually transmitted viral disease in the world. HPV infection of the genital epithelium is associated with genital warts and malignancies of the lower genital tract. To describe the distribution, phenotypic appearance and HPV type associated with genital warts in women. This was a prospective observational study of all women with genital warts who attended the Colposcopy Clinic, Groote Schuur Hospital, Cape Town, South Africa, during 2010 and fulfilled the inclusion and exclusion criteria. One hundred and thirteen women were tested for HPV using the Roche Linear Array HPV genotyping kit to determine the HPV genotypes causing genital warts. The median age of the women was 27 years (range 15 - 53); 90 (79.6%) were HIV-positive, and two-thirds were on antiretroviral treatment. Treatment involved ablation with topical agents, cauterisation or carbon dioxide laser. At 3 months' follow-up after treatment, 56.6% of the women, the majority of whom were HIV-positive, had recurrent/persistent disease. In both HIV-positive and HIV-negative women, HPV was detected in over 90% of cases. However, over half the HIV-positive women as opposed to 2/18 of the HIV-negative women were infected with multiple HPV genotypes. The commonest HPV genotypes in HIV-positive and HIV-negative women were types 11, 6, 89, 61, 55 and 62 and types 11 and 6, respectively. The majority of the patients were HIV-positive and had multiple HPV infections. While this did not alter the phenotypic appearance of the warts, recurrence/persistence after treatment was more common.

Diversity of human papillomavirus in the anal canal of men: The HIM study

PubMed Central

Sichero, Laura; Nyitray, Alan G.; Nunes, Emily Montosa; Nepal, Bal; Ferreira, Silvaneide; Sobrinho, João S.; Baggio, Maria Luiza; Galan, Lenice; Silva, Roberto C.; Lazcano-Ponce, Eduardo; Giuliano, Anna R.; Villa, Luisa L.

2015-01-01

Human papillomavirus (HPV) infections are associated with development of anogenital lesions in men. There are no reports describing the distribution of non-alpha HPV types in the anal canal of a sexually diverse men group. The HIM (HPV in Men) Study is a multicenter study of the natural history of HPV infection in Brazil, Mexico and USA. At baseline, 12% of anal canal specimens PCR HPV-positive were not typed by the Roche Linear Array and were considered unclassified. Our goal was characterizing HPVs among these unclassified specimens at baseline and assess associations with participant socio-demographic and behavioral characteristics. Unclassified HPVs were typed by sequencing amplified PGMY09/11 products or cloning of PGMY/GP+ nested amplicons followed by sequencing. Further analysis was conducted using FAP primers. Of men with unclassified HPV at the anal canal, most (89.1%) were men who have sex with women (MSW). Readable sequences were produced for 62.8% of unclassified specimens, of which 75.2% were characterized HPV types. A total of 18, 26, and 3 different α-, β- and γ-HPV types were detected, respectively. Compared to older men (45-70 years), α-HPVs were more commonly detected among young men (18-30 years) whereas β-HPVs were more frequent among mid-adult men (31-44 years). β-HPVs were more common among heterosexual men (85.0%) than non-heterosexual men. β2-HPV types composed all β-HPVs detected among non-heterosexual men. The high prevalence of β-HPV in the anal canal of men who do not report receptive anal sex is suggestive of other forms of transmission that do not involve penile-anal intercourse. PMID:25698660

Long-term persistence of oral human papillomavirus type 16: the HPV Infection in Men (HIM) study.

PubMed

Pierce Campbell, Christine M; Kreimer, Aimée R; Lin, Hui-Yi; Fulp, William; O'Keefe, Michael T; Ingles, Donna J; Abrahamsen, Martha; Villa, Luisa L; Lazcano-Ponce, Eduardo; Giuliano, Anna R

2015-03-01

Persistent infection with oral HPV16 is believed to drive the development of most oropharyngeal cancers. However, patterns of oral HPV16 persistence remain understudied, particularly among HIV-negative individuals. Oral HPV16 persistence was evaluated among 1,626 participants of the HPV Infection in Men (HIM) Study. Twenty-three oral HPV16-positive men who provided an oral gargle sample on ≥2 study visits were included in the analysis. Archived oral samples from all follow-up visits were tested for HPV16 using Linear Array and INNO-LiPA detection methods. Persistence was evaluated using consecutive HPV16-positive visits held approximately 6 months apart and using the Kaplan-Meier method. Oral HPV16-positive men were aged 18 to 64 years [median, 36 years; interquartile range (IQR), 25-42] and were followed for a median of 44.4 months (IQR, 29.9-49.5). Of 13 incident infections, 4 (30.8%) persisted ≥12 months, 1 (10.0%) persisted ≥24 months, and none persisted ≥36 months [median infection duration, 7.3 months; 95% confidence interval (CI), 6.4-NA)]. Of 10 prevalent infections, 9 (90.0%) persisted ≥12 months, 8 (80.0%) persisted ≥24 months, 4 (57.1%) persisted ≥36 months, and 2 (40.0%) persisted ≥48 months (median infection duration, NA). Twelve-month persistence of incident infections increased significantly with age (Ptrend = 0.028). Prevalent oral HPV16 infections in men persisted longer than newly acquired infections, and persistence appeared to increase with age. These findings may explain the high prevalence of oral HPV observed at older ages. Understanding oral HPV16 persistence will aid in the identification of men at high-risk of developing HPV-related oropharyngeal cancer. ©2015 American Association for Cancer Research.

Concurrent oral human papilloma virus infection in patients with recurrent respiratory papillomatosis: a preliminary study.

PubMed

Born, Hayley; Ruiz, Ryan; Verma, Avanti; Taliercio, Salvatore; Achlatis, Stratos; Pitman, Michael; Gandonu, Sonate; Bing, Renjie; Amin, Milan R; Branski, Ryan C

2014-12-01

To determine oral human papilloma virus (HPV) colonization in patients with adult-onset recurrent respiratory papillomatosis (AO-RRP) and their long-term partners. Prospective, cohort study Patients with pathology-confirmed AO-RRP and a small cohort of their long-term partners were subjected to a standardized oral rinse and swab protocol to obtain oral epithelial cells. DNA from these samples was extracted and subjected to both qualitative analyses via multiplex polymerase chain reaction as well as to a commercially available linear array assay for the determination of specific HPV subtypes. Samples were collected from 27 patients with AO-RRP and six long-term sexual partners. Qualitative analysis of agarose gel products using a multiple genotype primer cocktail suggested the presence of HPV DNA in oral rinse or swabs in 26 patients (96%) and four partner samples (67%). A subset of these positive patient samples was then subjected to genotyping; a spectrum of HPV subtypes was observed. Interestingly, HPV81 was identified in many samples. Recent data suggest that less than 7% of the general population is HPV positive in the oral cavity. Our data suggest that the oral colonization rate is much higher in patients with AO-RRP. Additionally, long-term sexual partners of patients with RRP had a much higher rate of HPV positivity. These preliminary data may have implications for viral transmission and provide a framework for enhanced patient education as well as further investigation. 4. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Distribution of HPV genotypes in women with cervical cancer in Auckland, New Zealand; a review of 50 specimens between 2000-2006.

PubMed

Williamson, Deborah; Nagappan, Radhika; Sirikonda, Rao; Rahnama, Fahimeh; Thomas, Stephen; Lovell-Smith, Margaret; Croxson, Margaret

2011-02-01

In New Zealand, around two hundred women are diagnosed with cervical cancer annually, with approximately seventy deaths from cervical cancer per year. Our aim was to determine the distribution of oncogenic HPV genotypes in biopsy specimens from women with diagnosed cervical cancers in the Auckland region of New Zealand between 2000-2006. Confirmed cases of cervical carcinoma were identified from the local pathology register, and representative tissue samples were taken from these blocks. Sections were deparaffinised, and DNA was extracted according to standard protocols. Samples were subject to PCR amplification using L1 consensus primer sets MY09/11 and GP5/6. Further type-specific amplification was performed on positive samples, using an in-house primer sequence based on target sequences within the E6 gene. Remaining samples were typed by a Linear Array Assay, or by DNA sequencing. HPV DNA was detected in 100% of cases. In 49/50 samples, the HPV genotype was identified, with a total of 14 different HPV genotypes detectable. Together HPV-16 and 18 were found in 41/49 cases (83.6%) either singly or in combination. Our findings suggest that the distribution of HPV genotypes in New Zealand is similar to that of other geographic areas. Ongoing surveillance is warranted to ensure appropriate genotype selection for prophylactic HPV vaccinations. © 2010 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology © 2010 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Diversity of human papillomavirus in the anal canal of men: the HIM Study.

PubMed

Sichero, L; Nyitray, A G; Nunes, E M; Nepal, B; Ferreira, S; Sobrinho, J S; Baggio, M L; Galan, L; Silva, R C; Lazcano-Ponce, E; Giuliano, A R; Villa, L L

2015-05-01

Human papillomavirus (HPV) infections are associated with the development of anogenital lesions in men. There are no reports describing the distribution of non-α HPV types in the anal canal of a sexually diverse group of men. The HPV Infection in Men (HIM) Study is a multicentre study on the natural history of HPV infection in Brazil, Mexico, and the USA. At baseline, 12% of anal canal PCR HPV-positive specimens were not typed by the Roche Linear Array, and were considered to be unclassified. Our goals were to characterize HPVs among these unclassified specimens at baseline, and to assess associations with participant socio-demographic and behavioural characteristics. Unclassified HPVs were typed by sequencing of amplified PGMY09/11 products or cloning of PGMY/GP + nested amplicons followed by sequencing. Further analysis was conducted with FAP primers. Of men with unclassified HPV in the anal canal, most (89.1%) were men who have sex with women. Readable sequences were produced for 62.8% of unclassified specimens, of which 75.2% were characterized HPV types. Eighteen, 26 and three different α-HPV, β-HPV and γ-HPV types were detected, respectively. α-HPVs were more commonly detected among young men (18-30 years) than among older men (45-70 years), whereas β-HPVs were more frequent among mid-adult men (31-44 years). β-HPVs were more common among heterosexual men (85.0%) than among non-heterosexual men. All β-HPVs detected among non-heterosexual men were β2-HPV types. The high prevalence of β-HPV in the anal canal of men who do not report receptive anal sex is suggestive of other forms of transmission that do not involve penile-anal intercourse. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Association of cytologic grade of anal "Pap" smears with viral loads of human papillomavirus types 16, 18, and 52 detected in the same specimens from men who have sex with men.

PubMed

Utaipat, Utaiwan; Siriaunkgul, Sumalee; Supindham, Taweewat; Saokhieo, Pongpun; Chaidaeng, Butsayarat; Wongthanee, Antika; Settakorn, Jongkolnee; Sukpan, Kornkanok; Ruanpeng, Darin; Kosashunhanan, Natthapol; Chotirosniramit, Nuntisa; Sugandhavesa, Patcharaphan; Miura, Toshiyuki; Chariyalertsak, Suwat

2016-12-01

Human papilloma virus (HPV) load has been linked to cellular abnormalities of the uterine cervix, and proposed as predictors of HPV persistence and progression of dysplasia to cervical cancer. However, the association of HPV viral load and anal dysplasia and cancer has not been as thoroughly investigated. To examine the association of the viral loads of high-risk HPV types 16, 18, and 52, with the cytologic severity grading in anal-swab specimens of MSM with and without HIV-1 co-infection. A cross-sectional study recruited 200 MSM in northern Thailand from July 2012 to January 2013. Real-time qPCR amplified portion of the HPV E6E7 gene, as well as the human β-globin gene to validate adequacy of the anal specimens and to normalize interpatient viral-load comparisons. Genotyping by linear-array assay identified and distinguished types 16, 18, and 52. HPV-16, and -18 viral loads increased with respect to the abnormality of the cytologic diagnoses (p<0.05 for HPV-16, p<0.01 for HPV-18). HIV-1 positivity was associated with higher HPV-18 viral load (p=0.006). HPV-16 viral loads ≥10 2.24 copies per 5000 anal cells, and HPV-18 loads ≥10 3.15 , were independently associated with abnormal cytology on logistic regression (p=0.022, p=0.041, respectively). Positive predictive values were 85.2% (23/27) and 80.0% (44/55) for the high viral load of a particular HPV-16 and the combined HPV-16, -18 and -52 types, respectively. High viral loads of HPV types 16 and 18 appear to be associated with anal cytologic abnormalities. The clinical utility of HPV viral loads to predict risk for anal cancer remains to be determined by a larger prospective cohort with sufficient frequency of high-grade dysplasia. Copyright © 2016 Elsevier B.V. All rights reserved.

Human papillomavirus prevalence, viral load and pre-cancerous lesions of the cervix in women initiating highly active antiretroviral therapy in South Africa: a cross-sectional study.

PubMed

Moodley, Jennifer R; Constant, Deborah; Hoffman, Margaret; Salimo, Anna; Allan, Bruce; Rybicki, Ed; Hitzeroth, Inga; Williamson, Anna-Lise

2009-08-07

Cervical cancer and infection with human immunodeficiency virus (HIV) are both important public health problems in South Africa (SA). The aim of this study was to determine the prevalence of cervical squamous intraepithelial lesions (SILs), high-risk human papillomavirus (HR-HPV), HPV viral load and HPV genotypes in HIV positive women initiating anti-retroviral (ARV) therapy. A cross-sectional survey was conducted at an anti-retroviral (ARV) treatment clinic in Cape Town, SA in 2007. Cervical specimens were taken for cytological analysis and HPV testing. The Digene Hybrid Capture 2 (HC2) test was used to detect HR-HPV. Relative light units (RLU) were used as a measure of HPV viral load. HPV types were determined using the Roche Linear Array HPV Genotyping test. Crude associations with abnormal cytology were tested and multiple logistic regression was used to determine independent risk factors for abnormal cytology. The median age of the 109 participants was 31 years, the median CD4 count was 125/mm3, 66.3% had an abnormal Pap smear, the HR-HPV prevalence was 78.9% (Digene), the median HPV viral load was 181.1 RLU (HC2 positive samples only) and 78.4% had multiple genotypes. Among women with abnormal smears the most prevalent HR-HPV types were HPV types 16, 58 and 51, all with a prevalence of 28.5%. On univariate analysis HR-HPV, multiple HPV types and HPV viral load were significantly associated with the presence of low and high-grade SILs (LSIL/HSIL). The multivariate logistic regression showed that HPV viral load was associated with an increased odds of LSIL/HSIL, odds ratio of 10.7 (95% CI 2.0 - 57.7) for those that were HC2 positive and had a viral load of 181.1 RLU. Women initiating ARVs have a high prevalence of abnormal Pap smears and HR-HPV. Our results underscore the need for locally relevant, rigorous screening protocols for the increasing numbers of women accessing ARV therapy so that the benefits of ARVs are not partially offset by an excess risk in cervical cancer.

Country-Specific HPV-related Genital Disease Among Men Residing in Brazil, Mexico, and the United States: The HIM Study

PubMed Central

Sudenga, Staci L.; Torres, B. Nelson; Fulp, William J.; Silva, Roberto; Villa, Luisa L.; Lazcano-Ponce, Eduardo; Ingles, Donna J.; Stoler, Mark; Messina, Jane L.; Abrahamsen, Martha; Luiza Baggio, Maria; Salmeron, Jorge; Quiterio, Manuel; Giuliano, Anna R.

2017-01-01

The purpose of this study was to assess whether the incidence of histopathologically confirmed condyloma and penile intraepithelial neoplasia (PeIN) and rates of genital HPV infection progression to these lesions differs by country (Brazil, Mexico, and the U.S.). At each visit, lesions were biopsied and were categorized by pathologic diagnoses. The Linear Array genotyping method was used to identify HPV genotypes from genital swabs, while the INNO-LiPA HPV Genotyping Extra method was used for tissue specimens. Age-specific analyses were conducted for lesion incidence by country, with Kaplan–Meier estimation of cumulative incidence. The proportion of HPV infections that progressed to condyloma and PeIN, the median time to lesion development, and the incidence rates were estimated by country. When comparing demographic and sexual characteristics across the three countries, sexual orientation (p=0.008) and lifetime number of female sexual partners (p < 0.0001) were differentially associated with lesion incidence in the three countries. Condyloma incidence in Brazil and the U.S. decreased with age, while incidence remained constant across the lifespan in Mexico. There were no differences by country and age for PeIN incidence. HPV types 6 and 11 were the most common types to progress to condyloma, and HPV types 16, 6, and 11 were the most common types to progress to PeIN in all three countries. The continuous risk of condyloma and PeIN across all age groups and countries in this study emphasizes the need to ensure that strong HPV immunity, such as that obtained through vaccination, is maintained across the lifespan of men. PMID:27681815

Country-specific HPV-related genital disease among men residing in Brazil, Mexico and The United States: The HIM study.

PubMed

Sudenga, Staci L; Torres, B Nelson; Fulp, William J; Silva, Roberto; Villa, Luisa L; Lazcano-Ponce, Eduardo; Ingles, Donna J; Stoler, Mark; Messina, Jane L; Abrahamsen, Martha; Baggio, Maria Luiza; Salmeron, Jorge; Quiterio, Manuel; Giuliano, Anna R

2017-01-15

The purpose of this study was to assess whether the incidence of histopathologically confirmed condyloma and penile intraepithelial neoplasia (PeIN) and rates of genital HPV infection progression to these lesions differs by country (Brazil, Mexico and the U.S.). At each visit, lesions were biopsied and were categorized by pathologic diagnoses. The Linear Array genotyping method was used to identify HPV genotypes from genital swabs, while the INNO-LiPA HPV Genotyping Extra method was used for tissue specimens. Age-specific analyses were conducted for lesion incidence by country, with Kaplan-Meier estimation of cumulative incidence. The proportion of HPV infections that progressed to condyloma and PeIN, the median time to lesion development and the incidence rates were estimated by country. When comparing demographic and sexual characteristics across the three countries, sexual orientation (p = 0.008) and lifetime number of female sexual partners (p < 0.0001) were differentially associated with lesion incidence in the three countries. Condyloma incidence in Brazil and the U.S. decreased with age, while incidence remained constant across the lifespan in Mexico. There were no differences by country and age for PeIN incidence. HPV types 6 and 11 were the most common types to progress to condyloma and HPV types 16, 6 and 11 were the most common types to progress to PeIN in all three countries. The continuous risk of condyloma and PeIN across all age groups and countries in this study emphasizes the need to ensure that strong HPV immunity, such as that obtained through vaccination, is maintained across the lifespan of men. © 2016 UICC.

Human papillomavirus (HPV) DNA triage of women with atypical squamous cells of undetermined significance with Amplicor HPV and Hybrid Capture 2 assays for detection of high-grade lesions of the uterine cervix.

PubMed

Dufresne, Simon; Sauthier, Philippe; Mayrand, Marie-Hélène; Petignat, Patrick; Provencher, Diane; Drouin, Pierre; Gauthier, Philippe; Dupuis, Marie-Josée; Michon, Bertrand; Ouellet, Stéphan; Hadjeres, Rachid; Ferenczy, Alex; Franco, Eduardo L; Coutlée, François

2011-01-01

Up to 20% of women having a cytology smear showing atypical squamous cells of undetermined significance (ASC-US) and infected with high-risk human papillomavirus (HR HPV) have high-grade cervical intraepithelial neoplasia (CIN 2/3). Results obtained with the Amplicor HPV and Hybrid Capture 2 (HC-2) assays for HR HPV DNA detection in women referred to colposcopy for an ASC-US smear were compared. Cervical samples in PreservCyt were tested for the presence of 13 HR HPV types with HC-2, with Amplicor at three cutoffs for positivity (0.2, 1.0, and 1.5 optical density units), and for 36 genotypes with the Linear Array (LA). Of 396 eligible women, 316 did not have CIN, 47 had CIN 1, 29 had CIN 2/3, and 4 had CIN of unknown grade. HR HPV was detected in 129 (32.6%) and 164 (41.4%) samples with HC-2 and Amplicor HPV (cutoff, 0.2), respectively (P = 0.01). Overall, 112 specimens were positive and 215 were negative with the HC-2 and Amplicor HPV assays (agreement of 82.6%; 95% confidence interval [CI], 78.5 to 86.0). The clinical sensitivity and specificity of Amplicor HPV at cutoffs of 0.2, 1.0 and 1.5 and of HC-2 for detection of CIN 2/3 were 89.7% (95% CI, 72.8 to 97.2) and 62.5% (95% CI, 57.5 to 52.4), 89.7% (95% CI, 72.8 to 97.2) and 64.5% (95% CI, 59.4 to 69.2), 89.7% (95% CI, 72.8 to 97.2) and 64.7% (95% CI, 59.7 to 69.5), and 93.1% (95% CI, 77.0 to 99.2) and 72.2% (95% CI, 67.4 to 76.5), respectively. Both HR HPV detection tests identified women with ASC-US who would benefit the most from colposcopy. Women with persistent HR HPV infection need further investigation despite a first normal colposcopy.

Comparison of DNA testing strategies in monitoring human papillomavirus infection prevalence through simulation.

PubMed

Lin, Carol Y; Li, Ling

2016-11-07

HPV DNA diagnostic tests for epidemiology monitoring (research purpose) or cervical cancer screening (clinical purpose) have often been considered separately. Women with positive Linear Array (LA) polymerase chain reaction (PCR) research test results typically are neither informed nor referred for colposcopy. Recently, a sequential testing by using Hybrid Capture 2 (HC2) HPV clinical test as a triage before genotype by LA has been adopted for monitoring HPV infections. Also, HC2 has been reported as a more feasible screening approach for cervical cancer in low-resource countries. Thus, knowing the performance of testing strategies incorporating HPV clinical test (i.e., HC2-only or using HC2 as a triage before genotype by LA) compared with LA-only testing in measuring HPV prevalence will be informative for public health practice. We conducted a Monte Carlo simulation study. Data were generated using mathematical algorithms. We designated the reported HPV infection prevalence in the U.S. and Latin America as the "true" underlying type-specific HPV prevalence. Analytical sensitivity of HC2 for detecting 14 high-risk (oncogenic) types was considered to be less than LA. Estimated-to-true prevalence ratios and percentage reductions were calculated. When the "true" HPV prevalence was designated as the reported prevalence in the U.S., with LA genotyping sensitivity and specificity of (0.95, 0.95), estimated-to-true prevalence ratios of 14 high-risk types were 2.132, 1.056, 0.958 for LA-only, HC2-only, and sequential testing, respectively. Estimated-to-true prevalence ratios of two vaccine-associated high-risk types were 2.359 and 1.063 for LA-only and sequential testing, respectively. When designated type-specific prevalence of HPV16 and 18 were reduced by 50 %, using either LA-only or sequential testing, prevalence estimates were reduced by 18 %. Estimated-to-true HPV infection prevalence ratios using LA-only testing strategy are generally higher than using HC2-only or using HC2 as a triage before genotype by LA. HPV clinical testing can be incorporated to monitor HPV prevalence or vaccine effectiveness. Caution is needed when comparing apparent prevalence from different testing strategies.

Reverse-phase protein array profiling of oropharyngeal cancer and significance of PIK3CA mutations in HPV-associated head and neck cancer.

PubMed

Sewell, Andrew; Brown, Brandee; Biktasova, Asel; Mills, Gordon B; Lu, Yiling; Tyson, Darren R; Issaeva, Natalia; Yarbrough, Wendell G

2014-05-01

Human papilloma virus (HPV)-associated (HPV+) oropharyngeal squamous cell carcinomas (OPSCC) have different molecular and biologic characteristics and clinical behavior compared with HPV-negative (HPV-) OPSCC. PIK3CA mutations are more common in HPV(+) OPSCC. To define molecular differences and tumor subsets, protein expression and phosphorylation were compared between HPV(+) and HPV(-) OPSCC and between tumors with and without PIK3CA mutations. Expression of 137 total and phosphorylated proteins was evaluated by reverse-phase protein array in 29 HPV(+) and 13 HPV(-) prospectively collected OPSCCs. Forty-seven OPSCCs were tested for hotspot-activating mutations in PIK3CA and AKT. Activation of PIK3CA downstream targets and sensitivity to pathway inhibitors were determined in HPV(+) head and neck cancer cells overexpressing wild-type or mutant PIK3CA. Analyses revealed 41 differentially expressed proteins between HPV(+) and HPV(-) OPSCC categorized into functional groups: DNA repair, cell cycle, apoptosis, phosphoinositide 3-kinase (PI3K)/AKT/mTOR, and receptor kinase pathways. All queried DNA repair proteins were significantly upregulated in HPV(+) samples. A total of 8 of 33 HPV(+) and 0 of 14 HPV(-) tumors contained activating PIK3CA mutations. Despite all activating PIK3CA mutations occurring in HPV(+) samples, HPV(+) tumors had lower mean levels of activated AKT and downstream AKT target phosphorylation. Ectopic expression of mutant PIK3CA in HPV(+) cells increased mTOR, but not AKT activity. HPV E6/E7 overexpression inhibited AKT phosphorylation in HPV-negative cells. Mutant PIK3CA overexpressing cells were more sensitive to a dual PI3K/mTOR inhibitor compared with an AKT inhibitor. Protein expression analyses suggest that HPV(+) and HPV(-) OPSCC differentially activate DNA repair, cell cycle, apoptosis, PI3K/AKT/mTOR, and receptor kinase pathways. PIK3CA mutations are more common in HPV(+) OPSCC and are associated with activation of mTOR, but not AKT. These data suggest that inhibitors for mTOR may have activity against HPV(+) PIK3CA mutant oropharyngeal cancers. ©2014 AACR.

Prevalence and concordance of high-risk papillomavirus infection in male sexual partners of women diagnosed with high grade cervical lesions.

PubMed

López Diez, Elena; Pérez, Sonia; Iñarrea, Amparo; de la Orden, Angel; Castro, Máximo; Almuster, Sheila; Tortolero, Leonardo; Rodríguez, Moises; Montero, Ruben; Ojea, Antonio

2017-05-01

Little is known about the characteristics of high-risk papillomavirus (HR-HPV) infection in men. The aims of this cross-sectional study were: (a) to investigate HR-HPV prevalence and genotype distribution in men, sexual partners of women presenting with high-grade cervical intraepithelial neoplasia (HG-CIN), according to epidemiological characteristics, and (b) to assess type-specific concordance between partners. A total of 125 men were recruited within the first 6 months after HG-CIN diagnosis of their partner. Samples from the coronal sulcus, glans penis shaft, and scrotum were tested with linear array HPV genotyping assay (Roche Diagnostics, Mannheim, Germany). Type-specific concordance within 120 couples was studied. Epidemiological factors were evaluated by multivariate logistic regression analysis. SPSS 19 (IBM, Chicago, USA). The prevalence of HR-HPV infection in males was 50.4% (63/125). HPV16/53/52/51/66/31 were the most frequent genotypes (24/10.4/9.6/8.8/8/7.2%, respectively). Current smoking was associated with an increased risk for HR-HPV infection in men (38.2% (21/55) vs 60% (42/70), OR 2.4, p=0.025). Among 60 infected couples, 62% shared at least one genotype: 41.7% couples were concordantly HPV16 positive and 18.3% were HPV16 negative (kappa value: 0.21). The proportion of women with the same genotype as their male partner was higher than the proportion of men sharing the same genotype as their female partner: 58.7% (37/63) vs 30.8% (37/120), p<0.0001. Sexual partners of women with HG-CIN are a significant reservoir and vector of HPV infection, a fact that could contribute to making viral clearance more difficult to achieve in their partners after treatment of their HG-CIN lesions. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Reduced rate of human papillomavirus infection and genetic overtransmission of TP53 72C polymorphic variant lower cervical cancer incidence.

PubMed

Alsbeih, Ghazi A; Al-Harbi, Najla M; Bin Judia, Sara S; Khoja, Hatim A; Shoukri, Mohamed M; Tulbah, Asma M

2017-07-01

Cervical cancer is a predominantly human papillomavirus (HPV)-driven disease worldwide. However, its incidence is unexplainably low in western Asia, including Saudi Arabia. Using this paradigm, we investigated the role of HPV infection rate and host genetic predisposition in TP53 G72C single nucleotide polymorphism (SNP) presumed to affect cancer incidence. Patients treated between 1990 and 2012 were reviewed, and a series of 232 invasive cervical cancer cases were studied and compared with 313 matched controls without cancer. SNP was genotyped by way of direct sequencing. HPV linear array analysis was used to detect and genotype HPV in tumor samples. The incidence of cervical cancer revealed bimodal peaks at 42.5 years, with a slighter rebound at 60.8 years. Among all cases, 77% were HPV-positive and 16 HPV genotypes were detected-mostly genotypes 16 (75%) and 18 (9%)-with no difference by age, histology, or geographical region. Although the TP53 G72C genotype was not associated with overall cervical cancer risk, it was significantly associated with HPV positivity (odds ratio, 0.57; 95% confidence interval, 0.36-0.90; P = .016). Furthermore, the variant C allele was significantly overtransmitted in the population (P < .0003). Cervical cancer incidence displays bimodal curve peaking at a young age with secondary rebound at older age. The combination of relative low HPV infection and variant TP53 72C allele overtransmission provide a plausible explanation for the low incidence of cervical cancer in our population. Therefore, HPV screening and host SNP genotyping may provide more relevant biomarkers to gauge the risk of developing cervical cancer. Cancer 2017;123:2459-66. © 2017 American Cancer Society. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Cell-cycle and suppressor proteins expression in uterine cervix in HIV/HPV co-infection: comparative study by tissue micro-array (TMA).

PubMed

Nicol, Alcina F; Pires, Andréa Rodrigues Cordovil; de Souza, Simone R; Nuovo, Gerard J; Grinsztejn, Beatriz; Tristão, Aparecida; Russomano, Fabio B; Velasque, Luciane; Lapa e Silva, José R; Pirmez, Claude

2008-10-07

The oncoproteins of human papillomavirus (HPVs) directly effect cell-cycle control. We hypothesize that regulatory and cell cycle protein expression might be additionally modified in the cervix of HIV/HPV co-infected women. We analyzed the expression of Rb, p27, VEGF and Elf-1 transcriptor factor by immunohistochemistry in 163 paraffin-embeded cervical samples using Tissue Micro-Array (TMA) and correlated this to HIV-1 and HPV infection. HIV/HPV co-infection was associated with a significant increase in expression (p < 0.001) of VEGF and p27 in both low and high grade CIN when compared to the cervices of women infected by HPV alone. Decreased Rb expression was evident with increased CIN grade in the cervices of women infected with HPV alone (p = 0.003 average of cells/mm2 in CIN I: 17.9, CIN II/III: 4.8, and tumor 3.9). Rb expression increased 3-fold for both low and high grade CIN with HPV/HIV-1 co-infection compared to HPV infection alone but did not reach statistical significance. There was a significant increase in Elf-1 expression in HPV+/HIV- women with CIN II/III and tumor (average of cells/mm2 in CIN I: 63.8; CIN II/III: 115.7 and tumor: 112.0, p = 0.005), in comparison to controls. Co-infection of HPV and HIV leads to significant increase in the VEGF and p27 expression when compared to HPV+/HIV-negative infection that could facilitate viral persistence and invasive tumor development.

The Need for Cervical Cancer Control in HIV-Positive and HIV-Negative Women from Romania by Primary Prevention and by Early Detection Using Clinically Validated HPV/DNA Tests.

PubMed

Ursu, Ramona Gabriela; Onofriescu, Mircea; Luca, Alexandru; Prisecariu, Liviu Jany; Sălceanu, Silvia Olivia; Nemescu, Dragoş; Iancu, Luminiţa Smaranda

2015-01-01

In Romania, a country with no organized national surveillance program regarding cervical cancer, the early diagnosis of HPV (Human Papilloma Virus) infections is a major requirement, especially in HIV-infected women. The objective of this study was to determine the HPV prevalence and type distribution in young HIV-positive women and to assess the difference in the risk factors for developing cervical cancer compared to those of HIV-negative women. We conducted one cross-sectional cohort study from June 2013-September 2014, including 1,032 women: 992 HIV- women who were 36.5 years old (limits: 17 ÷ 84) and 40 HIV + women who were 22.9 years old (limits: 17 ÷ 30) with iatrogenic HIV infected. We detected HPV types with the Linear Array HPV Genotyping test (Roche, Romania). DNA/HPV was detected in 18/40 (45%) of the HIV+ patients and in 350/992 (35.2%) of the HIV- patients (OR = 1.5, 95%CI 0.76÷2.96). After age adjustment, the overall HPV prevalence was 51.6% in HIV+ versus 63.2% in HIV- women aged under 25, and 22.2% in HPV+ versus 47.2% in HIV- women aged 25-34. We detect HIV being a risk factor for acquiring multiple HPV type infections (OR = 2.30, 95% CI 0.88÷5.97). The eight most common HPV types (high-risk, and low-risk) for women below age 30, HIV+ / - were: HPV 16, 18, 31, 51, 58, 68, and 6 and 82 respectively. To assess the risk factors of HIV-positive women for acquiring HPV infection, we analyzed the CD4/μL, ARN/HIV copies/μL, the age group, the number of sexual partners, smoking, and the type of HPV infection (single versus multiple infections). We found that the number of sexual partners and smoking are statistically significant risk factors. Even though there are no significant differences regarding the prevalence of HPV infection in HIV + versus HIV - patients, multiple infections were more frequent in the first group. In our study group young HIV-infected patients under HAART therapy, high number of sexual partners (more than 3) and smoking were detected to be risk factors. Future organized screening for HPV infection using sensitive and specific methods are necessary at the national level in Romania.

Anal cytological abnormalities and epidemiological correlates among men who have sex with men at risk for HIV-1 infection.

PubMed

Donà, Maria Gabriella; Benevolo, Maria; Vocaturo, Amina; Palamara, Guido; Latini, Alessandra; Giglio, Amalia; Moretto, Domenico; Rollo, Francesca; Impara, Giampaolo; Ensoli, Fabrizio; Pimpinelli, Fulvia; Di Carlo, Aldo; Giuliani, Massimo

2012-10-16

The incidence of anal cancer, a Human Papillomavirus (HPV)-related neoplasia, has been increasing in recent decades, mainly in men who have sex with men (MSM). Cytological changes of the anal epithelium induced by HPV can be detected through an anal pap smear. This study aimed to evaluate the prevalence and epidemiological correlates of anal cytological abnormalities among relatively young MSM at risk for HIV-1 infection, to help clarify whether or not this population deserves further investigation to assess the presence of anal cancer precursor lesions. MSM were recruited among attendees of a large STI clinic for a HIV-1 screening program. Anal samples, collected with a Dracon swab in PreservCyt, were used both for liquid-based cytology and HPV testing by the Linear Array HPV Genotyping Test. Data regarding socio-demographic characteristics and sexual behavior were collected in face-to-face interviews. A total of 346 MSM were recruited (median age 32 years). Overall, 72.5% of the individuals had an anal HPV infection, with 56.1% of them being infected by oncogenic HPV genotypes. Anal cytological abnormalities were found in 29.8% of the cases (16.7% ASC-US and 13.1% L-SIL). Presence of ASC-US+ was strongly associated with infection by any HPV type (OR = 4.21, 95% CI: 1.97-9.23), and particularly by HPV 16 and/or 18 (OR = 5.62, 95% CI: 2.33-13.81). A higher proportion of ASC-US+ was found in older MSM, in those with a higher number of lifetime partners and in those with a history of ano-genital warts. However, none of these variables or the others analyzed showed any significant association with abnormal cytological findings. The presence of anal cytological abnormalities in about one third of the recruited MSM and their strong association with HPV infection, in particular that caused by HPV 16 and/or 18, might provide a further complement to the data that now support the introduction of HPV vaccination among MSM to protect them from the development of HPV-associated diseases. Additional studies are needed to determine whether and how screening for anal cancer precursor lesions should be performed in younger MSM.

Prevalence and predictors of squamous intraepithelial lesions of the cervix in HIV-infected women in Lusaka, Zambia

PubMed Central

Parham, Groesbeck P.; Sahasrabuddhe, Vikrant V.; Mwanahamuntu, Mulindi H.; Shepherd, Bryan E.; Hicks, Michael L.; Stringer, Elizabeth M.; Vermund, Sten H.

2009-01-01

Objectives HIV-infected women living in resource-constrained nations like Zambia are now accessing antiretroviral therapy and thus may live long enough for HPV-induced cervical cancer to manifest and progress. We evaluated the prevalence and predictors of cervical squamous intraepithelial lesions (SIL) among HIV-infected women in Zambia. Methods We screened 150 consecutive, non-pregnant HIV-infected women accessing HIV/AIDS care services in Lusaka, Zambia. We collected cervical specimens for cytological analysis by liquid-based monolayer cytology (ThinPrep Pap Test®) and HPV typing using the Roche Linear Array® PCR assay. Results The median age of study participants was 36 years (range 23-49 years) and their median CD4+ count was 165/μL (range 7-942). The prevalence of SIL on cytology was 76% (114/150), of which 23.3% (35/150) women had low-grade SIL, 32.6% (49/150) had high-grade SIL, and 20% (30/150) had lesions suspicious for squamous cell carcinoma (SCC). High-risk HPV types were present in 85.3% (128/150) women. On univariate analyses, age of the participant, CD4+ cell count, and presence of any high-risk HPV type were significantly associated with the presence of severely abnormal cytological lesions (i.e., high-grade SIL and lesions suspicious for SCC). Multivariable logistic regression modeling suggested the presence of any high-risk HPV type as an independent predictor of severely abnormal cytology (adjusted OR: 12.4, 95% CI 2.62-58.1, p=0.02). Conclusions The high prevalence of abnormal squamous cytology in our study is one of the highest reported in any population worldwide. Screening of HIV-infected women in resource-constrained settings like Zambia should be implemented to prevent development of HPV-induced SCC. PMID:16875716

[Human papillomavirus associated cervix uteri morbidity in Hungary: epidemiology and correlation with the HPV types and the simultaneous cytological diagnosis].

PubMed

Szentirmay, Zoltán; Veleczki, Zsuzsa; Kásler, Miklós

2017-08-01

Persistent infection of human papillomavirus is known to cause cervical intraepithelial neoplasia or cancer in the cervix uteri and other HPV-associated cancers in different localization. Based on epidemiological and biological data, principally the high risk HPV is responsible for development of cervical these cancers. However, we have no information about the frequently distribution of different HPV types and what is the correlation between the HPV types and cytological diagnosis in cervical intraepithelial neoplasia (CIN). In this paper, we are going to present new data involving incidence and mortality of HPV-associated cancers during the period of 2009-2015 in Hungary. We are also going to investigate the correlation of cervical cytological diagnosis and HPV typing, and the preventive effect of HPV vaccination. The epidemiological data spring from the National Cancer Registry. HPV typing was performed by Linear Array HPV Genotyping Test. Simultaneous cytological diagnosis and HPV typing was carried out on 2048 cytological samples collected in period of 2009-2016. According to the epidemiologic data, the most frequently occurring HPV-associated cancer is the laryngeal carcinoma in man, and the cervical cancer in woman in Hungary. During the 2009-2015 time intervals, the frequency distribution of head and neck cancers was not changed in man, but the incidence of tongue root squamous cell carcinomas was gradually increasing in woman. We have defined the clinical significance of single and simultaneously multiple HPV infection and have investigated the correlation of the HPV frequency distribution and cytological diagnosis in CIN. It was found that in the cytological negativity of probably/possibly carcinogen pHR-HPV group classified by IACR was much more frequent as in HR-HPV group (56% versus 47%). The presence of simultaneous multiplex HPV infection betokens an increased cancer risk. According to the international publications, the ratio of HPV16 just twice as big as in cervical cancer, what we found in CIN (60% versus 30%). The frequency order of the HPV18 is 2nd in cancer, and 9th in CIN. Comparing the frequency distribution of HR/pHR-HPVs in cervical cancer and CIN, the HR-HPV35 is very rarely occurring in CIN, the pHR-HPV56, 66, and 73 is more frequently seen in CIN as in carcinoma. Appreciated the preventive value of anti-HPV vaccines, we have found a significant differences in group with 1 HPV/sample and in group with more than 1 HPV/sample. The frequency distribution of tongue root squamous cell carcinoma and cervical cancer was gradually increasing in woman. The overall preventive effect of 9-valent vaccine is 80.3%. This preventive value should be higher because of the transformation ability of the different HPV types is not same. Out of consideration for HPV incidence in cancer, the preventive effect of 9-valent or 4-valent vaccines might reach to 93% or 73%. However, the pHR-HPVs are biologically active, it is not sufficient for the inclusion of these HPV types into population-wide HPV-DNA based cervical screening programs. Orv Hetil. 2017; 158(31): 1213-1221.

Development of a photodiode array biochip using a bipolar semiconductor and its application to detection of human papilloma virus.

PubMed

Baek, Taek Jin; Park, Pan Yun; Han, Kwi Nam; Kwon, Ho Taik; Seong, Gi Hun

2008-03-01

We describe a DNA microarray system using a bipolar integrated circuit photodiode array (PDA) chip as a new platform for DNA analysis. The PDA chip comprises an 8 x 6 array of photodiodes each with a diameter of 600 microm. Each photodiode element acts both as a support for an immobilizing probe DNA and as a two-dimensional photodetector. The usefulness of the PDA microarray platform is demonstrated by the detection of high-risk subtypes of human papilloma virus (HPV). The polymerase chain reaction (PCR)-amplified biotinylated HPV target DNA was hybridized with the immobilized probe DNA on the photodiode surface, and the chip was incubated in an anti-biotin antibody-conjugated gold nanoparticle solution. The silver enhancement by the gold nanoparticles bound to the biotin of the HPV target DNA precipitates silver metal particles at the chip surfaces, which block light irradiated from above. The resulting drop in output voltage depends on the amount of target DNA present in the sample solution, which allows the specific detection and the quantitative analysis of the complementary target DNA. The PDA chip showed high relative signal ratios of HPV probe DNA hybridized with complementary target DNA, indicating an excellent capability in discriminating HPV subtypes. The detection limit for the HPV target DNA analysis improved from 1.2 nM to 30 pM by changing the silver development time from 5 to 10 min. Moreover, the enhanced silver development promoted by the gold nanoparticles could be applied to a broader range of target DNA concentration by controlling the silver development time.

Anal human papillomavirus in HIV-uninfected men who have sex with men: incidence and clearance rates, duration of infection, and risk factors.

PubMed

Donà, M G; Vescio, M F; Latini, A; Giglio, A; Moretto, D; Frasca, M; Benevolo, M; Rollo, F; Colafigli, M; Cristaudo, A; Giuliani, M

2016-12-01

Little is known regarding the natural history of anal human papillomavirus (HPV) infection. We aimed to evaluate incidence and clearance rates, their risk factors, and duration of anal HPV infection in HIV-uninfected men who have sex with men (MSM). A longitudinal study was conducted. Anal samples were analysed using the Linear Array HPV Genotyping test. Incidence and clearance rates, and corresponding risk factors, were estimated using a two-state Markov model. Overall, 155 MSM (median age 33.4 years) attending the largest sexually transmitted infection (STI) centre in Rome, Italy, were followed for a median of 12.2 months (Q1-Q3: 7.0-18.1). Incidence and clearance rates for any HPV were 85.6 (95% CI: 58.4-125.4) and 35.6 (95% CI: 24.7-51.5) × 1000 person-months, respectively; the median duration of infection was 9.4 months (Q1-Q3: 7.5-12.1). Receptive anal sex emerged as the only risk factor for the acquisition of any HPV (Hazard Ratio, HR = 2.65, 95% CI: 1.16-6.06). The incidence rates for carcinogenic and non-carcinogenic types were 42.3 (95% CI: 29.2-61.4) and 29.2 (95% CI: 19.5-43.7) × 1000 person-months, respectively (p = 0.13); their clearance rates were 62.9 (95% CI: 45.1-87.7) and 65.7 (95% CI: 47.4-91.0) × 1000 person-months, respectively (p = 0.83). HPV16 showed the lowest clearance rate among carcinogenic types (59.7 × 1000 person-months), and a duration of infection of 16.8 months. In conclusion, a higher incidence rate was observed for carcinogenic compared to non-carcinogenic HPV types, although the difference was not significant. HPV16 emerged as the type with the longest duration of infection and the lowest clearance rate among carcinogenic types. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Human papillomavirus mRNA and DNA testing in women with atypical squamous cells of undetermined significance: A prospective cohort study.

PubMed

Thomsen, Louise T; Dehlendorff, Christian; Junge, Jette; Waldstrøm, Marianne; Schledermann, Doris; Frederiksen, Kirsten; Kjaer, Susanne K

2016-10-15

In this prospective cohort study, we compared the performance of human papillomavirus (HPV) mRNA and DNA testing of women with atypical squamous cells of undetermined significance (ASC-US) during cervical cancer screening. Using a nationwide Danish pathology register, we identified women aged 30-65 years with ASC-US during 2005-2011 who were tested for HPV16/18/31/33/45 mRNA using PreTect HPV-Proofer (n = 3,226) or for high-risk HPV (hrHPV) DNA using Hybrid Capture 2 (HC2) (n = 9,405) or Linear Array HPV-Genotyping test (LA) (n = 1,533). Women with ≥1 subsequent examination in the register (n = 13,729) were followed for up to 9.5 years for high-grade cervical intraepithelial neoplasia (CIN) or cancer. After 3 years' follow-up, mRNA testing had higher specificity for CIN3 or worse (CIN3+) than HC2 testing (88.1% [95% confidence interval (CI): 86.8-89.6%] versus 59.3% [95% CI: 58.1-60.4%]) and higher positive predictive value (PPV) (38.2% [95% CI: 33.8%-43.1%] versus 19.5% [95% CI: 17.8-20.9%]). However, the sensitivity of mRNA testing was lower than that of HC2 testing (66.7% [95% CI: 59.3-74.5%] versus 97.0% [95% CI: 95.5-98.4%]), and women testing mRNA negative had higher 3-year risk for CIN3+ than those testing HC2 negative (3.2% [95% CI: 2.2-4.2%] versus 0.5% [95% CI: 0.3-0.7%]). Patterns were similar after 18 months and 5 years'; follow-up; for CIN2+ and cancer as outcomes; across all age groups; and when comparing mRNA testing to hrHPV DNA testing using LA. In conclusion, the HPV16/18/31/33/45 mRNA test is not optimal for ASC-US triage due to its low sensitivity and the substantial risk for precancer following a negative test. © 2016 UICC.

Type-Specific Detection of 30 Oncogenic Human Papillomaviruses by Genotyping both E6 and L1 Genes

PubMed Central

Peng, Junping; Gao, Lei; Guo, Junhua; Wang, Ting; Wang, Ling; Yao, Qing; Zhu, Haijun

2013-01-01

Human papillomavirus (HPV) is the principal cause of invasive cervical cancer and benign genital lesions. There are currently 30 HPV types linked to cervical cancer. HPV infection also leads to other types of cancer. We developed a 61-plex analysis of these 30 HPV types by examining two genes, E6 and L1, using MassARRAY matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) (PCR-MS). Two hundred samples from homosexual males (HM) were screened by PCR-MS and MY09/MY11 primer set-mediated PCR (MY-PCR) followed by sequencing. One hundred thirty-five formalin-fixed, paraffin-embedded (FFPE) cervical cancer samples were also analyzed by PCR-MS, and results were compared to those of the commercially available GenoArray (GA) assay. One or more HPV types were identified in 64.5% (129/200) of the samples from HM. Comprising all 30 HPV types, PCR-MS detected 51.9% (67/129) of samples with multiple HPV types, whereas MY-PCR detected only one single HPV type in these samples. All PCR-MS results were confirmed by MY-PCR. In the cervical cancer samples, PCR-MS and GA detected 97% (131/135) and 90.4% (122/135) of HPV-positive samples, respectively. PCR-MS and GA results were fully concordant for 122 positive and 4 negative samples. The sequencing results for the 9 samples that tested negative by GA were completely concordant with the positive PCR-MS results. Multiple HPV types were identified in 25.2% (34/135) and 55.6% (75/135) of the cervical cancer samples by GA and PCR-MS, respectively, and results were confirmed by sequencing. The new assay allows the genotyping of >1,000 samples per day. It provides a good alternative to current methods, especially for large-scale investigations of multiple HPV infections and degraded FFPE samples. PMID:23152557

Anal cytological lesions and HPV infection in individuals at increased risk for anal cancer.

PubMed

Donà, Maria Gabriella; Benevolo, Maria; Latini, Alessandra; Rollo, Francesca; Colafigli, Manuela; Frasca, Mirko; Zaccarelli, Mauro; Giglio, Amalia; Moretto, Domenico; Pescarmona, Edoardo; Cristaudo, Antonio; Giuliani, Massimo

2018-04-25

Anal cytology may be useful for evaluating lesions associated with human papillomavirus (HPV) in individuals at increased risk for anal cancer. Liquid-based cytology was used to assess anal cytological lesions among human immunodeficiency virus (HIV)-infected and HIV-uninfected men who have sex with men (MSM). The Linear Array HPV genotyping test was used for HPV detection. This cross-sectional study included 1021 MSM, of whom 388 were HIV-infected (38.0%). Anal cytological lesions (atypical squamous cells of undetermined significance or more severe [ASCUS+]) were observed in 32.5% and 53.2% of the HIV-uninfected and HIV-infected individuals, respectively (P < .0001). The highest ASCUS + prevalence was observed among ≥45-year-old HIV-uninfected MSM (37.3%) and 25-to 29-year-old HIV-infected MSM (66.7%). High-grade squamous intraepithelial lesions (HSILs) peaked in ≥ 45-year-old HIV-uninfected subjects and 35- to 39-year-old HIV-infected subjects. Individuals with anal infections with high-risk (HR) HPV types were 3 to 4 times more likely to have an ASCUS + report. An HPV-16 and/or HPV-18 infection increased the odds of HSIL or more severe cytology (HSIL+) for HIV-infected MSM almost 4 times. MSM concurrently infected with HR and low-risk HPVs were significantly more likely to have low-grade squamous intraepithelial lesions or more severe cytology (LSIL+) than those infected with only HR types. No significant associations were found between cytological abnormalities and the HIV load and nadir and current CD4 + counts. The prevalence of anal cytological lesions is high in MSM, even in HIV-infected individuals treated with combined antiretroviral therapy. In these subjects, HSILs occur more frequently and at a younger age in comparison with HIV-uninfected counterparts. Specific diagnostic procedures should be implemented to manage individuals at increased risk for anal cancer with an abnormal anal Papanicolaou test. Cancer Cytopathol 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Possible Synergistic Interactions Among Multiple HPV Genotypes in Women Suffering from Genital Neoplasia

PubMed

Hajia, Massoud; Sohrabi, Amir

2018-03-27

Objective: Persistence of HPV infection is the true cause of cervical disorders. It is reported that competition may exist among HPV genotypes for colonization. This survey was designed to establish the multiple HPV genotype status in our community and the probability of multiple HPV infections involvement. Methods: All multiple HPV infections were selected for investigation in women suffering from genital infections referred to private laboratories in Tehran, Iran. A total of 160 multi HPV positive specimens from cervical scraping were identified by the HPV genotyping methods, "INNO-LiPA and Geno Array". Result: In present study, HPV 6 (LR), 16 (HR), 53 (pHR), 31 (HR) and 11 (LR) were included in 48.8% of detected infections as the most five dominant genotypes. HPV 16 was detected at the highest rate with genotypes 53, 31 and 52, while HPV 53 appeared linked with HPV 16, 51 and 56 in concurrent infections. It appears that HPV 16 and 53 may have significant tendencies to associate with each other rather than with other genotypes. Analysis of the data revealed there may be some synergistic interactions with a few particular genotypes such as "HPV 53". Conclusion: Multiple HPV genotypes appear more likely to be linked with development of cervical abnormalities especially in patients with genital infections. Since, there are various patterns of dominant HPV genotypes in different regions of world, more investigations of this type should be performed for careHPV programs in individual countries. Creative Commons Attribution License

Human Papillomavirus Genotyping Using an Automated Film-Based Chip Array

PubMed Central

Erali, Maria; Pattison, David C.; Wittwer, Carl T.; Petti, Cathy A.

2009-01-01

The INFINITI HPV-QUAD assay is a commercially available genotyping platform for human papillomavirus (HPV) that uses multiplex PCR, followed by automated processing for primer extension, hybridization, and detection. The analytical performance of the HPV-QUAD assay was evaluated using liquid cervical cytology specimens, and the results were compared with those results obtained using the digene High-Risk HPV hc2 Test (HC2). The specimen types included Surepath and PreservCyt transport media, as well as residual SurePath and HC2 transport media from the HC2 assay. The overall concordance of positive and negative results following the resolution of indeterminate and intermediate results was 83% among the 197 specimens tested. HC2 positive (+) and HPV-QUAD negative (−) results were noted in 24 specimens that were shown by real-time PCR and sequence analysis to contain no HPV, HPV types that were cross-reactive in the HC2 assay, or low virus levels. Conversely, HC2 (−) and HPV-QUAD (+) results were noted in four specimens and were subsequently attributed to cross-contamination. The most common HPV types to be identified in this study were HPV16, HPV18, HPV52/58, and HPV39/56. We show that the HPV-QUAD assay is a user friendly, automated system for the identification of distinct HPV genotypes. Based on its analytical performance, future studies with this platform are warranted to assess its clinical utility for HPV detection and genotyping. PMID:19644025

Human papillomavirus genotyping using an automated film-based chip array.

PubMed

Erali, Maria; Pattison, David C; Wittwer, Carl T; Petti, Cathy A

2009-09-01

The INFINITI HPV-QUAD assay is a commercially available genotyping platform for human papillomavirus (HPV) that uses multiplex PCR, followed by automated processing for primer extension, hybridization, and detection. The analytical performance of the HPV-QUAD assay was evaluated using liquid cervical cytology specimens, and the results were compared with those results obtained using the digene High-Risk HPV hc2 Test (HC2). The specimen types included Surepath and PreservCyt transport media, as well as residual SurePath and HC2 transport media from the HC2 assay. The overall concordance of positive and negative results following the resolution of indeterminate and intermediate results was 83% among the 197 specimens tested. HC2 positive (+) and HPV-QUAD negative (-) results were noted in 24 specimens that were shown by real-time PCR and sequence analysis to contain no HPV, HPV types that were cross-reactive in the HC2 assay, or low virus levels. Conversely, HC2 (-) and HPV-QUAD (+) results were noted in four specimens and were subsequently attributed to cross-contamination. The most common HPV types to be identified in this study were HPV16, HPV18, HPV52/58, and HPV39/56. We show that the HPV-QUAD assay is a user friendly, automated system for the identification of distinct HPV genotypes. Based on its analytical performance, future studies with this platform are warranted to assess its clinical utility for HPV detection and genotyping.

Ethnic and geographic variations in HPV prevalence and genotype distribution in north-western Yunnan, China.

PubMed

Baloch, Zulqarnain; Yuan, Tao; Wang, Binghui; Tai, Wenlin; Feng, Yue; Liu, Yanqing; Li, Xiao; Feng, Yue; Liu, Li; Zhang, A-mei; Wu, Xiaomei; Xia, Xueshan

2016-03-01

The prevalence and genotype distribution of human papillomavirus (HPV) vary throughout the world. To assess the prevalence and genotype distribution of HPV among three ethnic groups in two geographic locations in north-western Yunnan, we recruited 522 women in Shangri-le (n = 255) and Lijiang (n = 267). PCR amplification of HPV DNA was performed on cervical cells from these women using two consensus primer systems (MY09/11 and GP5/6). Amplified-HPV DNA was genotyped using the HPV GenoArray test. Geographically, the HPV prevalence was significantly higher (P = 0.002) among Shangri-le women than among Lijiang women. Infections with high-risk (HR)-HPV and with multiple HPV genotypes were also significantly more common (P = 0.001) among women in Shangri-le than women in Lijiang. Additionally, the prevalence of overall, HR-HPV, and single genotype HPV infections was significantly higher (P = 0.001) among Tibetan women than among Naxi and Han women. HPV-16 and HPV-33 were significantly more frequent in Shangri-le women compared with Lijiang (P = 0.006) women. In addition, HPV-16 (9.81%) and HPV-33 (5.88%) were significantly more prevalent in Tibetan women than in Naxi and Han women. Here, for the first time, we highlight the significant variation in the prevalence and genotype distribution of HPV in various populations in the north-western region of Yunnan Province. © 2015 Wiley Periodicals, Inc.

Impact of HPV infection on oral squamous cell carcinoma.

PubMed

Götz, Carolin; Drecoll, Enken; Straub, Melanie; Bissinger, Oliver; Wolff, Klaus-Dietrich; Kolk, Andreas

2016-11-22

Head and neck squamous cell carcinomas (HNSCC) are often divided by their aetiology. Noxae associated collectives are compared with the human papilloma virus (HPV)-associated group, whereas different localisations of oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinomas are mostly discussed as one single group. Our aim was to show that classification by aetiology is not appropriate for OSCC. HPV DNA was detected by PCR in 7 (3.47%) patients, and we identified 12 (5.94%) positive (+) cases by p16INK4a immunostaining. Only 4 (1.98%) of the p16INK4a+ cases were + for HPV using PCR. Our homogenous collective of OSCC allowed us to compare HPV+ and HPV negative (-) patients without creating bias for tumour localisation, age, gender or tumour stage. After testing OSCC samples for HPV positivity, we compared the results of two commonly used HPV detection methods, p16INK4a immunostaining and HPV DNA-related PCR, on 202 OSCC patients. HPV subtypes were determined with an HPV LCD Array Kit. Clinicopathological features of the patients were analysed, and the disease specific survival rates (DSS) for HPV+ and HPV- patients were obtained. p16INK4a immunostaining is a not a reliable HPV detection method for OSCC. Positive p16INK4a immunostaining did not agree with + results from PCR of HPV DNA. Furthermore, the influence of HPV-related oncogenic transformation in OSCC is overestimated. The significance of HPV infection remains clinically unclear, and its influence on survival rates is not relevant to OSCC cases.

Vaccination with Human Papillomavirus Pseudovirus-Encapsidated Plasmids Targeted to Skin Using Microneedles

PubMed Central

Kines, Rhonda C.; Zarnitsyn, Vladimir; Johnson, Teresa R.; Pang, Yuk-Ying S.; Corbett, Kizzmekia S.; Nicewonger, John D.; Gangopadhyay, Anu; Chen, Man; Liu, Jie; Prausnitz, Mark R.; Schiller, John T.; Graham, Barney S.

2015-01-01

Human papilloma virus-like particles (HPV VLP) serve as the basis of the current licensed vaccines for HPV. We have previously shown that encapsidation of DNA expressing the model antigen M/M2 from respiratory syncytial virus (RSV) in HPV pseudovirions (PsV) is immunogenic when delivered intravaginally. Because the HPV capsids confer tropism for basal epithelium, they represent attractive carriers for vaccination targeted to the skin using microneedles. In this study we asked: 1) whether HPV16 VLP administered by microneedles could induce protective immune responses to HPV16 and 2) whether HPV16 PsV-encapsidated plasmids delivered by microneedles could elicit immune responses to both HPV and the antigen delivered by the transgene. Mice immunized with HPV16 VLP coated microneedles generated robust neutralizing antibody responses and were protected from HPV16 challenge. Microneedle arrays coated with HPV16-M/M2 or HPV16-F protein (genes of RSV) were then tested and dose-dependent HPV and F-specific antibody responses were detected post-immunization, and M/M2-specific T-cell responses were detected post RSV challenge, respectively. HPV16 PsV-F immunized mice were fully protected from challenge with HPV16 PsV and had reduced RSV viral load in lung and nose upon intranasal RSV challenge. In summary, HPV16 PsV-encapsidated DNA delivered by microneedles induced neutralizing antibody responses against HPV and primed for antibody and T-cell responses to RSV antigens encoded by the encapsidated plasmids. Although the immunogenicity of the DNA component was just above the dose response threshold, the HPV-specific immunity was robust. Taken together, these data suggest microneedle delivery of lyophilized HPV PsV could provide a practical, thermostable combined vaccine approach that could be developed for clinical evaluation. PMID:25785935

Vaccination with human papillomavirus pseudovirus-encapsidated plasmids targeted to skin using microneedles.

PubMed

Kines, Rhonda C; Zarnitsyn, Vladimir; Johnson, Teresa R; Pang, Yuk-Ying S; Corbett, Kizzmekia S; Nicewonger, John D; Gangopadhyay, Anu; Chen, Man; Liu, Jie; Prausnitz, Mark R; Schiller, John T; Graham, Barney S

2015-01-01

Human papilloma virus-like particles (HPV VLP) serve as the basis of the current licensed vaccines for HPV. We have previously shown that encapsidation of DNA expressing the model antigen M/M2 from respiratory syncytial virus (RSV) in HPV pseudovirions (PsV) is immunogenic when delivered intravaginally. Because the HPV capsids confer tropism for basal epithelium, they represent attractive carriers for vaccination targeted to the skin using microneedles. In this study we asked: 1) whether HPV16 VLP administered by microneedles could induce protective immune responses to HPV16 and 2) whether HPV16 PsV-encapsidated plasmids delivered by microneedles could elicit immune responses to both HPV and the antigen delivered by the transgene. Mice immunized with HPV16 VLP coated microneedles generated robust neutralizing antibody responses and were protected from HPV16 challenge. Microneedle arrays coated with HPV16-M/M2 or HPV16-F protein (genes of RSV) were then tested and dose-dependent HPV and F-specific antibody responses were detected post-immunization, and M/M2-specific T-cell responses were detected post RSV challenge, respectively. HPV16 PsV-F immunized mice were fully protected from challenge with HPV16 PsV and had reduced RSV viral load in lung and nose upon intranasal RSV challenge. In summary, HPV16 PsV-encapsidated DNA delivered by microneedles induced neutralizing antibody responses against HPV and primed for antibody and T-cell responses to RSV antigens encoded by the encapsidated plasmids. Although the immunogenicity of the DNA component was just above the dose response threshold, the HPV-specific immunity was robust. Taken together, these data suggest microneedle delivery of lyophilized HPV PsV could provide a practical, thermostable combined vaccine approach that could be developed for clinical evaluation.

1 H MR spectroscopy in cervical carcinoma using external phase array body coil at 3.0 Tesla: Prediction of poor prognostic human papillomavirus genotypes.

PubMed

Lin, Gigin; Lai, Chyong-Huey; Tsai, Shang-Yueh; Lin, Yu-Chun; Huang, Yu-Ting; Wu, Ren-Chin; Yang, Lan-Yan; Lu, Hsin-Ying; Chao, Angel; Wang, Chiun-Chieh; Ng, Koon-Kwan; Ng, Shu-Hang; Chou, Hung-Hsueh; Yen, Tzu-Chen; Hung, Ji-Hong

2017-03-01

To assess the clinical value of proton ( 1 H) MR spectroscopy in cervical carcinomas, in the prediction of poor prognostic human papillomavirus (HPV) genotypes as well as persistent disease following concurrent chemoradiotherapy (CCRT). 1 H MR spectroscopy using external phase array coil was performed in 52 consecutive cervical cancer patients at 3 Tesla (T). Poor prognostic HPV genotypes (alpha-7 species or absence of HPV infection) and persistent cervical carcinoma after CCRT were recorded. Statistical significance was calculated with the Mann-Whitney two-sided nonparametric test and areas under the receiver operating characteristics curve (AUC) analysis. A 4.3-fold (P = 0.032) increased level of methyl resonance at 0.9 ppm was found in the poor prognostic HPV genotypes, mainly attributed to the presence of HPV18, with a sensitivity of 75%, a specificity of 81%, and an AUC of 0.76. Poor prognostic HPV genotypes were more frequently observed in patients with adeno-/adenosquamous carcinoma (Chi-square, P < 0.0001). In prediction of the four patients with persistent disease after CCRT, elevated methyl resonance demonstrated a sensitivity of 100%, a specificity of 74%, and an AUC of 0.82. 1 H MR spectroscopy at 3T can be used to depict the elevated lipid resonance levels in cervical carcinomas, as well as help to predict the poor prognostic HPV genotypes and persistent disease following CCRT. Further large studies with longer follow up times are warranted to validate our initial findings. 1 J. Magn. Reson. Imaging 2017;45:899-907. © 2016 International Society for Magnetic Resonance in Medicine.

Linear viral load increase of a single HPV-type in women with multiple HPV infections predicts progression to cervical cancer.

PubMed

Depuydt, Christophe E; Thys, Sofie; Beert, Johan; Jonckheere, Jef; Salembier, Geert; Bogers, Johannes J

2016-11-01

Persistent high-risk human papillomavirus (HPV) infection is strongly associated with development of high-grade cervical intraepithelial neoplasia or cancer (CIN3+). In single type infections, serial type-specific viral-load measurements predict the natural history of the infection. In infections with multiple HPV-types, the individual type-specific viral-load profile could distinguish progressing HPV-infections from regressing infections. A case-cohort natural history study was established using samples from untreated women with multiple HPV-infections who developed CIN3+ (n = 57) or cleared infections (n = 88). Enriched cell pellet from liquid based cytology samples were subjected to a clinically validated real-time qPCR-assay (18 HPV-types). Using serial type-specific viral-load measurements (≥3) we calculated HPV-specific slopes and coefficient of determination (R(2) ) by linear regression. For each woman slopes and R(2) were used to calculate which HPV-induced processes were ongoing (progression, regression, serial transient, transient). In transient infections with multiple HPV-types, each single HPV-type generated similar increasing (0.27copies/cell/day) and decreasing (-0.27copies/cell/day) viral-load slopes. In CIN3+, at least one of the HPV-types had a clonal progressive course (R(2)  ≥ 0.85; 0.0025copies/cell/day). In selected CIN3+ cases (n = 6), immunostaining detecting type-specific HPV 16, 31, 33, 58 and 67 RNA showed an even staining in clonal populations (CIN3+), whereas in transient virion-producing infections the RNA-staining was less in the basal layer compared to the upper layer where cells were ready to desquamate and release newly-formed virions. RNA-hybridization patterns matched the calculated ongoing processes measured by R(2) and slope in serial type-specific viral-load measurements preceding the biopsy. In women with multiple HPV-types, serial type-specific viral-load measurements predict the natural history of the different HPV-types and elucidates HPV-genotype attribution. © 2016 UICC.

Ski protein levels increase during in vitro progression of HPV16-immortalized human keratinocytes and in cervical cancer

PubMed Central

Chen, Yi; Pirisi, Lucia; Creek, Kim E.

2013-01-01

We compared the levels of the Ski oncoprotein, an inhibitor of transforming growth factor-beta (TGF-β) signaling, in normal human keratinocytes (HKc), HPV16 immortalized HKc (HKc/HPV16), and differentiation resistant HKc/HPV16 (HKc/DR) in the absence and presence of TGF-β. Steady-state Ski protein levels increased in HKc/HPV16 and even further in HKc/DR, compared to HKc. TGF-β treatment of HKc, HKc/HPV16, and HKc/DR dramatically decreased Ski. TGF-β-induced Ski degradation was delayed in HKc/DR. Ski and phospho-Ski protein levels are cell cycle dependent with maximal Ski expression and localization to centrosomes and mitotic spindles during G2/M. ShRNA knock down of Ski in HKc/DR inhibited cell proliferation. More intense nuclear and cytoplasmic Ski staining and altered Ski localization were found in cervical cancer samples compared to adjacent normal tissue in a cervical cancer tissue array. Overall, these studies demonstrate altered Ski protein levels, degradation and localization in HPV16-transformed human keratinocytes and in cervical cancer. PMID:23809940

HPV genotypes and associated cervical cytological abnormalities in women from the Pearl River Delta region of Guangdong province, China: a cross-sectional study

PubMed Central

2014-01-01

Background It is important to understand the specific HPV genotype distribution in screen-detected lesions. HPV Genotype is helpful for separating HPV-positive women at greater risk of cancer from those who can regress spontaneously and for preventing cervical cancer at early stage. The aim of this study was to investigate the high-risk HPV genotype distribution among cervical cytology abnormality in Pearl River Delta Region, Southern China Methods 5585 HPV-infected women were screened from 77069 women in Pearl River Delta Region. Information was obtained from 3226 screened subjects through questionnaires and personal interviews. Exfoliated cervical cells were collected by doctors for HPV test with MassARRAY (Sequenom, Sandiego, CA) technique based on the matrix-assisted laser desorption/ionization time-of flight (MALDI-TOF) mass spectrometry (MS). The ThinPrep cytology test was performed to screen for cervical cancer. Unconditional logistic was used to determine the most common HPV carcinogenic types. Results Of the 3226 HPV-positive samples tested, 1744 (54.1%) with normal cervical cytology, 1482 (45.9%) with abnormal cytology. The five most common HPV types in this study were HPV16 (20.2%), HPV52 (17.1%), HPV58 (13.2%), HPV18 (9.5%), HPV6 (7.6%). Overall, HPV16 (OR = 10.5, 95% CI: 3.7 ~ 29.6), HPV33 (OR = 9.1, 95% CI: 2.8 ~ 29.2), HPV58 (OR = 6.3, 95% CI: 2.1 ~ 18.6), HPV31 (OR = 4.5, 95% CI: 1.3 ~ 15.5), multiple genotype infection (OR = 3.0, 95% CI: 1.7 ~ 14.7), especially HPV16 and HPV33, increased the risk of cytology abnormalities. Conclusions HPV16, HPV31, HPV33, HPV58, and multiple HPV genotype infection increased the risk of cytology abnormalities in Pearl River Delta Region and might be useful for the screening, preventing, treating, and monitoring of pre-cancer lesions in southern China. PMID:25016305

HPV Literacy: The Role of English Proficiency in Korean American Immigrant Women.

PubMed

Lee, Hee Yun; Choi, Y Joon; Yoon, Young Ji; Oh, Jennifer

2018-06-01

Although Korean American women have one of the highest cervical cancer incidence and mortality rates among all Asian American and non-Hispanic White women, they are less likely to receive the human papillomavirus (HPV) vaccine to prevent cervical cancer. This study aimed to examine Korean American women's HPV literacy and factors related to HPV literacy to identify targeted intervention strategies. A quota sampling strategy was used to recruit 243 Korean American women aged 19-85 years in the Atlanta, Georgia, metropolitan area. Multiple linear regression analysis was conducted using Andersen's Behavioral Model of Health Services Use to examine factors associated with HPV literacy. HPV literacy of Korean American immigrant women was moderate, and knowledge about HPV detection items was particularly low. Age was the only predisposing factor that had a significantly negative association with HPV literacy, whereas education level and English proficiency had a significant positive relationship with HPV literacy. Health status as a need factor was significantly positively associated with HPV literacy.

[Detection and typing by molecular biology of human papillomavirus in genital samples].

PubMed

Suárez Moya, A; Esquivias Gómez, J I; Vidart Aragón, J A; Picazo de la Garza, J J

2006-06-01

Recently, there has been a marked increase in human papillomavirus (HPV) infection, and the etiological relationship between some HPV genotypes and genital cancer has been confirmed. Therefore, we used current molecular biology techniques to evaluate the prevalence of these viruses and their genotype in genital samples. We processed 401 genital samples from 281 women and 120 men, all with a diagnosis compatible with HPV infection. Virus was detected using PCR, and positive samples were typed using an array technique which enabled us to detect the 35 most common types of mucous-associated HPV. Of the 401 patients studied, 185 (46.1%) were positive, and only one type of HPV was detected in 133 cases. We found that 41.6% of the women and 56.7% of the men were positive. A total of 260 HPVs were typed; 154 were high oncogenic risk. They infected 16 men (23.5%) and 88 women (75.2%). The difference was statistically significant (p<0.001). Type 6 HPV was the most frequently detected en 64 cases, followed by HVP 16 in 52 cases. We found a 46% prevalence of HPV infection. More than half of these patients were infected by high-risk HPV. The presence of high-risk HPV was significantly higher in women.

Characterization of transformation related genes in oral cancer cells.

PubMed

Chang, D D; Park, N H; Denny, C T; Nelson, S F; Pe, M

1998-04-16

A cDNA representational difference analysis (cDNA-RDA) and an arrayed filter technique were used to characterize transformation-related genes in oral cancer. From an initial comparison of normal oral epithelial cells and a human papilloma virus (HPV)-immortalized oral epithelial cell line, we obtained 384 differentially expressed gene fragments and arrayed them on a filter. Two hundred and twelve redundant clones were identified by three rounds of back hybridization. Sequence analysis of the remaining clones revealed 99 unique clones corresponding to 69 genes. The expression of these transformation related gene fragments in three nontumorigenic HPV-immortalized oral epithelial cell lines and three oral cancer cell lines were simultaneously monitored using a cDNA array hybridization. Although there was a considerable cell line-to-cell line variability in the expression of these clones, a reliable prediction of their expression could be made from the cDNA array hybridization. Our study demonstrates the utility of combining cDNA-RDA and arrayed filters in high-throughput gene expression difference analysis. The differentially expressed genes identified in this study should be informative in studying oral epithelial cell carcinogenesis.

Serial measurement of type-specific human papillomavirus load enables classification of cervical intraepithelial neoplasia lesions according to occurring human papillomavirus-induced pathway.

PubMed

Verhelst, Stefanie; Poppe, Willy A J; Bogers, Johannes J; Depuydt, Christophe E

2017-03-01

This retrospective study examined whether human papillomavirus (HPV) type-specific viral load changes measured in two or three serial cervical smears are predictive for the natural evolution of HPV infections and correlate with histological grades of cervical intraepithelial neoplasia (CIN), allowing triage of HPV-positive women. A cervical histology database was used to select consecutive women with biopsy-proven CIN in 2012 who had at least two liquid-based cytology samples before the diagnosis of CIN. Before performing cytology, 18 different quantitative PCRs allowed HPV type-specific viral load measurement. Changes in HPV-specific load between measurements were assessed by linear regression, with calculation of coefficient of determination (R) and slope. All infections could be classified into one of five categories: (i) clonal progressing process (R≥0.85; positive slope), (ii) simultaneously occurring clonal progressive and transient infection, (iii) clonal regressing process (R≥0.85; negative slope), (iv) serial transient infection with latency [R<0.85; slopes (two points) between 0.0010 and -0.0010 HPV copies/cell/day], and (v) transient productive infection (R<0.85; slope: ±0.0099 HPV copies/cell/day). Three hundred and seven women with CIN were included; 124 had single-type infections and 183 had multiple HPV types. Only with three consecutive measurements could a clonal process be identified in all CIN3 cases. We could clearly demonstrate clonal regressing lesions with a persistent linear decrease in viral load (R≥0.85; -0.003 HPV copies/cell/day) in all CIN categories. Type-specific viral load increase/decrease in three consecutive measurements enabled classification of CIN lesions in clonal HPV-driven transformation (progression/regression) and nonclonal virion-productive (serial transient/transient) processes.

Prognostic significance of c-KIT in vulvar cancer: bringing this molecular marker from bench to bedside

PubMed Central

2012-01-01

Background Vulvar carcinomas are rare tumors, and there is limited data regarding molecular alterations. To our knowledge there are no published studies on c-KIT and squamous cell carcinomas of the vulva (VSCC). Although there are a significant number of other tumor types which express c-KIT, there remains controversy as to its relationship to patient outcome. Thus, we wished to investigate such controversial findings to determine the prognostic importance of c-KIT by evaluating its protein and mRNA expression in VSCCs, correlating these findings with clinicopathological features and Human Papillomavirus (HPV) infection. Methods c-KIT expression was scored by immunohistochemistry (IHC) as positive or negative in 139 formalin-fixed paraffin-embedded (FFPE) cases of vulvar carcinomas arrayed in a tissue microarray (TMA) using the DAKO® A4502 rabbit polyclonal c-KIT antibody (diluted 1:100). c-KIT mRNA was evaluated by qRT-PCR in 34 frozen samples from AC Camargo Hospital Biobank (17 tumoral and 17 non-tumoral samples) using TaqMan probes–Applied Biosystems [Hs00174029_m1]. HPV genotyping was assessed in 103 samples using Linear Array® HPV Genotyping Test kit (Roche Molecular Diagnostics, Basel, Switzerland). All results obtained were correlated with clinical and pathological data of the patients. Results c-KIT protein was positive by immunohistochemistry in 70.5% of the cases and this was associated with a higher global survival (p = 0.007), a higher recurrence-free survival (p < 0.0001), an absence of associated lesions (p = 0.001), lymph node metastasis (p = 0.0053), and HPV infection (p = 0.034). Furthermore, c-KIT mRNA quantitation revealed higher levels of transcripts in normal samples compared to tumor samples (p = 0,0009). Conclusions Our findings indicate that those vulvar tumors staining positively for c-KIT present better prognosis. Thus, positivity of c-KIT as evaluated by IHC may be a good predictor for use of more conservative surgery techniques and lymph node dissection in vulvar cancer. So part of the essence of our study is to see the possibility of translating our current results from the bench to the bedside. This will help provide patients a more appropriate, less mutilating treatment, in order to keep the maximum physical and psychic quality as possible to these women. PMID:22839358

Comparison of detection methods for HPV status as a prognostic marker for loco-regional control after radiochemotherapy in patients with HNSCC.

PubMed

Linge, Annett; Schötz, Ulrike; Löck, Steffen; Lohaus, Fabian; von Neubeck, Cläre; Gudziol, Volker; Nowak, Alexander; Tinhofer, Inge; Budach, Volker; Sak, Ali; Stuschke, Martin; Balermpas, Panagiotis; Rödel, Claus; Bunea, Hatice; Grosu, Anca-Ligia; Abdollahi, Amir; Debus, Jürgen; Ganswindt, Ute; Lauber, Kirsten; Pigorsch, Steffi; Combs, Stephanie E; Mönnich, David; Zips, Daniel; Baretton, Gustavo B; Buchholz, Frank; Krause, Mechthild; Belka, Claus; Baumann, Michael

2018-04-01

To compare six HPV detection methods in pre-treatment FFPE tumour samples from patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who received postoperative (N = 175) or primary (N = 90) radiochemotherapy. HPV analyses included detection of (i) HPV16 E6/E7 RNA, (ii) HPV16 DNA (PCR-based arrays, A-PCR), (iii) HPV DNA (GP5+/GP6+ qPCR, (GP-PCR)), (iv) p16 (immunohistochemistry, p16 IHC), (v) combining p16 IHC and the A-PCR result and (vi) combining p16 IHC and the GP-PCR result. Differences between HPV positive and negative subgroups were evaluated for the primary endpoint loco-regional control (LRC) using Cox regression. Correlation between the HPV detection methods was high (chi-squared test, p < 0.001). While p16 IHC analysis resulted in several false positive classifications, A-PCR, GP-PCR and the combination of p16 IHC and A-PCR or GP-PCR led to results comparable to RNA analysis. In both cohorts, Cox regression analyses revealed significantly prolonged LRC for patients with HPV positive tumours irrespective of the detection method. The most stringent classification was obtained by detection of HPV16 RNA, or combining p16 IHC with A-PCR or GP-PCR. This approach revealed the lowest rate of recurrence in patients with tumours classified as HPV positive and therefore appears most suited for patient stratification in HPV-based clinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Opportunity for catch-up HPV vaccination in young women after first delivery.

PubMed

Rama, Cristina Helena; Villa, Luisa L; Pagliusi, Sonia; Andreoli, Maria A; Costa, Maria C; Thomann, Patricia; Alves, Venancio A F; Longatto-Filho, Adhemar; Eluf-Neto, Jose

2010-07-01

Early age at first delivery has been identified as a risk factor for high-risk HPV-type infection and cervical cancer development. A cross-sectional study was carried out in a large public maternity hospital in São Paulo, Brazil. During June 2006 to February 2007, 301 women aged 15-24 years who gave birth to their first child were recruited between 43 and 60 days after delivery. Detection of HPV DNA in cervical specimens was performed using a standardised PCR protocol with PGMY09/11 primers. The association of selected factors with HPV infection was assessed by using a Generalised Linear Model. HPV DNA was detected in 58.5% (95% CI 52.7% to 64.0%) of the enrolled young women. The most common types of HPV found were: HPV16, HPV51, HPV52, HPV58 and HPV71. The overall prevalence of HPV types targeted by the HPV prophylactic vaccines was: HPV 16-12.0%, HPV 18- 2.3% and HPV 6 and 11 4.3%. In the multivariate analysis, only age (inversely, p for trend=0.02) and smoking habits were independently associated with HPV infection. The findings show that these young primiparous women had high cervical HPV prevalence, suggesting that this is a high-risk group for cervical cancer development. Nevertheless, 17.3% were positive for any of the four HPV types included in HPV vaccines (HPV6, 11, 16 or 18), with 13.3% positive for HPV 16 or 18 and only 1.0% having both vaccine related-oncogenic HPV types. Thus, young primiparous women could benefit from catch-up HPV vaccination programmes.

Nip the HPV encoded evil in the cancer bud: HPV reshapes TRAILs and signaling landscapes

PubMed Central

2013-01-01

HPV encoded proteins can elicit ectopic protein–protein interactions that re-wire signaling pathways, in a mode that promotes malignancy. Moreover, accumulating data related to HPV is now providing compelling substantiation of a central role played by HPV in escaping immunosurveillance and impairment of apoptotic response. What emerges is an intricate network of Wnt, TGF, Notch signaling cascades that forms higher-order ligand–receptor complexes routing downstream signaling in HPV infected cells. These HPV infected cells are regulated both extracellularly by ligand receptor axis and intracellularly by HPV encoded proteins and impair TRAIL mediated apoptosis. We divide this review into different sections addressing how linear signaling pathways integrate to facilitate carcinogenesis and compounds that directly or indirectly reverse these aberrant interactions offer new possibilities for therapy in cancer. Although HPV encoded proteins mediated misrepresentation of pathways is difficult to target, improved drug-discovery platforms and new technologies have facilitated the discovery of agents that can target dysregulated pathways in HPV infected cervical cancer cells, thus setting the stage for preclinical models and clinical trials. PMID:23773282

Genotype distribution of human papillomavirus (HPV) in histological sections of cervical intraepithelial neoplasia and invasive cervical carcinoma in Madrid, Spain

PubMed Central

2012-01-01

Background Human Papillomavirus (HPV) genotype distribution and co-infection occurrence was studied in cervical specimens from the city of Madrid (Spain), as a contribution to the knowledge of Human Papillomavirus genotype distribution and prevalence of carcinogenic HPV types in cervical lesions in Spain. Methods A total of 533 abnormal specimens, from the Hospital General Universitario “Gregorio Marañón” of Madrid, were studied. These included 19 benign lesions, 349 cervical intraepithelial neoplasias 1 (CIN1), 158 CIN2-3 and 7 invasive cervical carcinomas (ICC). HPV genotyping was performed using PCR and tube array hybridization. Results We detected 20 different HPV types: 13 carcinogenic high-risk HPV types (HR-HPVs), 2 probably carcinogenic high-risk HPV types (PHR-HPVs) and 5 carcinogenic low-risk HPV types (LR-HPVs). The most frequent HPV genotypes found in all specimens were HPV16 (26.0%), 31 (10.7%) and 58 (8.0%). HPV 18 was only detected in 5.0%. Co-infections were found in 30.7% of CIN 1 and 18.4% cases of CIN2-3. The highest percentage of HR HPVs was found in those specimens with a CIN2-3 lesion (93.7%). Conclusion As our study shows the current tetravalent vaccine could be effective in our geographical area for preventing all the invasive cervical carcinomas. In addition, upon the estimates of the important presence of other HR-HPV types – such as 31, 58, 33 and 52 – in different preneoplasic lesions the effectiveness of HPV vaccination in our geographical area, and others with similar genotype distribution, should be limited. PMID:23167826

ERAP1 overexpression in HPV-induced malignancies: A possible novel immune evasion mechanism.

PubMed

Steinbach, Alina; Winter, Jan; Reuschenbach, Miriam; Blatnik, Renata; Klevenz, Alexandra; Bertrand, Miriam; Hoppe, Stephanie; von Knebel Doeberitz, Magnus; Grabowska, Agnieszka K; Riemer, Angelika B

2017-01-01

Immune evasion of tumors poses a major challenge for immunotherapy. For human papillomavirus (HPV)-induced malignancies, multiple immune evasion mechanisms have been described, including altered expression of antigen processing machinery (APM) components. These changes can directly influence epitope presentation and thus T-cell responses against tumor cells. To date, the APM had not been studied systematically in a large array of HPV + tumor samples. Therefore in this study, systematic expression analysis of the APM was performed on the mRNA and protein level in a comprehensive collection of HPV16 + cell lines. Subsequently, HPV + cervical tissue samples were examined by immunohistochemistry. ERAP1 (endoplasmic reticulum aminopeptidase 1) was the only APM component consistently altered - namely overexpressed - in HPV16 + tumor cell lines. ERAP1 was also found to be overexpressed in cervical intraepithelial neoplasia and cervical cancer samples; expression levels were increasing with disease stage. On the functional level, the influence of ERAP1 expression levels on HPV16 E7-derived epitope presentation was investigated by mass spectrometry and in cytotoxicity assays with HPV16-specific T-cell lines. ERAP1 overexpression did not cause a complete destruction of any of the HPV epitopes analyzed, however, an influence of ERAP1 overexpression on the presentation levels of certain HPV epitopes could be demonstrated by HPV16-specific CD8 + T-cells. These showed enhanced killing toward HPV16 + CaSki cells whose ERAP1 expression had been attenuated to normal levels. ERAP1 overexpression may thus represent a novel immune evasion mechanism in HPV-induced malignancies, in cases when presentation of clinically relevant epitopes is reduced by overactivity of this peptidase.

Ski protein levels increase during in vitro progression of HPV16-immortalized human keratinocytes and in cervical cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Yi; Pirisi, Lucia; Creek, Kim E., E-mail: creekk@sccp.sc.edu

2013-09-15

We compared the levels of the Ski oncoprotein, an inhibitor of transforming growth factor-beta (TGF-β) signaling, in normal human keratinocytes (HKc), HPV16 immortalized HKc (HKc/HPV16), and differentiation resistant HKc/HPV16 (HKc/DR) in the absence and presence of TGF-β. Steady-state Ski protein levels increased in HKc/HPV16 and even further in HKc/DR, compared to HKc. TGF-β treatment of HKc, HKc/HPV16, and HKc/DR dramatically decreased Ski. TGF-β-induced Ski degradation was delayed in HKc/DR. Ski and phospho-Ski protein levels are cell cycle dependent with maximal Ski expression and localization to centrosomes and mitotic spindles during G2/M. ShRNA knock down of Ski in HKc/DR inhibited cellmore » proliferation. More intense nuclear and cytoplasmic Ski staining and altered Ski localization were found in cervical cancer samples compared to adjacent normal tissue in a cervical cancer tissue array. Overall, these studies demonstrate altered Ski protein levels, degradation and localization in HPV16-transformed human keratinocytes and in cervical cancer. - Highlights: • Ski oncoprotein levels increase during progression of HPV16-transformed cells. • Ski and phospho-Ski protein levels are cell cycle dependent. • Ski knock-down in HPV16-transformed keratinocytes inhibited cell proliferation. • Cervical cancer samples overexpress Ski.« less

Nonendemic HPV-Positive Nasopharyngeal Carcinoma: Association With Poor Prognosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stenmark, Matthew H., E-mail: stenmark@med.umich.edu; McHugh, Jonathan B.; Schipper, Matthew

Purpose: To investigate the relationship between human papillomavirus (HPV) and Epstein-Barr virus (EBV) in nonendemic nasopharyngeal carcinoma (NPC) and assess the prognostic implications of viral status. Methods and Materials: Paraffin-embedded tumor specimens from 62 patients with primary NPC diagnosed between 1985 and 2011 were analyzed for EBV and high-risk HPV. EBV status was determined by the use of in situ hybridization for EBV encoded RNA. HPV status was assessed with p16 immunohistochemistry and multiplex polymerase chain reaction MassArray for determination of HPV type. Proportional hazards models were used to compare the risk of death among patients as stratified by viralmore » status. Results: Of 61 evaluable tumors, 26 (43%) were EBV-positive/HPV-negative, 18 (30%) were HPV-positive/EBV-negative, and 17 (28%) were EBV/HPV-negative. EBV and HPV infection was mutually exclusive. HPV positivity was significantly correlated with World Health Organization grade 2 tumors, older age, and smoking (all P<.001). The racial distribution of the study population was 74% white, 15% African American, and 11% Asian/Middle Eastern. Among HPV-positive patients, 94% were white. At a median follow-up time of 7 years, HPV-positive and EBV/HPV-negative tumors exhibited worse outcomes than did EBV-positive tumors, including decreased overall survival (hazard ratio [HR] 2.98, P=.01; and HR 3.89, P=.002), progression-free survival (HR 2.55, P=.02; and HR 4.04, P<.001), and locoregional control (HR 4.01, P=.03; and HR 6.87, P=.001). Conclusion: In our Midwestern population, high-risk HPV infection may play an etiologic role in the development of nonendemic, EBV-negative NPC. Compared with EBV-positive NPC, HPV-positive and EBV/HPV-negative NPC are associated with worse outcomes. A larger confirmatory study is needed to validate these findings.« less

The Prevalence and Genotype of Human Papillomavirus from Patients with Genital Warts in Eastern Guangdong Province.

PubMed

Luo, Zhao-Yun; Chen, Qiang; Yang, Hui; Lin, Min; Chen, Chan-Yu; Yang, Chun; Yang, Li-Ye

2015-01-01

Low-risk human papillomavirus (LR-HPV) infection is the main cause of genital warts. LR- HPV genotypes 6 and 11 are associated with genital warts, but there have only been a few published studies about the genotype-specific prevalence of HPV in genital warts in China. The objective of our study was to assess the prevalence of HPV genotypes for clinical cases involving both men and women and to evaluate the potential benefit of a quadrivalent (genotypes 6, 11, 16, and 18) HPV vaccine in eastern Guangdong province of China. A total of 696 eligible patients with genital warts were enrolled during the period Aug 2009 through Oct 2014. Specimens were collected from genital warts, the HPV GenoArray test was used for HPV detection and genotyping, which could detect 21 HPV genotypes, including genotypes 6, 11, 16, and 18. Among the 696 cases, 675 samples were successfully genotyped. The median age of patients was 32.1 years (range, 16-67 years). The most prevalent genotypes were HPV-6 (285/675, 42.2%), HPV-11 (265/675, 39.3%), HPV-52 (52/675, 7.7%), HPV-16 (51/675, 7.56%), HPV-81 (50/675, 7.40%) and HPV-58 (37/675, 5.48%). Low-risk genotypes predominated, with a prevalence of 96.59%. The cumulative prevalence of genotypes 6 and 11 was 78.7% (531/675), the cumulative prevalence of genotypes 16 and 18 was 11.6% (78/675), and the cumulative prevalence of genotypes 6, 11, 16, and 18 was 82.5% (557/675). Our results provide strong evidence that, in eastern Guangdong, different from Western countries, the most prevalent low risk HPV genotypes in patients with genital warts are 6, 11 and 81. The quadrivalent HPV vaccine could prevent 82.5% of genital warts in eastern Guangdong.

Human papillomavirus 16 E6 modulates the expression of miR-496 in oropharyngeal cancer.

PubMed

Mason, Dayna; Zhang, Xiaoying; Marques, Tânia Monteiro; Rose, Barbara; Khoury, Samantha; Hill, Meredith; Deutsch, Fiona; Lyons, J Guy; Gama-Carvalho, Margarida; Tran, Nham

2018-06-20

Human papillomavirus (HPV), notably type 16, is a risk factor for up to 75% of oropharyngeal squamous cell carcinomas (SCC). It has been demonstrated that small non-coding RNAs known as microRNAs play a vital role in the cellular transformation process. In this study, we used an LNA array to further investigate the impact of HPV16 on the expression of microRNAs in oropharyngeal (tonsillar) cancer. A number of miRNAs were found to be deregulated, with miR-496 showing a four-fold decrease. Over-expression of the high risk E6 oncoprotein down-regulated miR-496, impacting upon the post-transcriptional control of the transcription factor E2F2. These HPV specific miRNAs were integrated with the HPV16 interactome to identify possible mechanistic pathways. These analyses provide insights into novel molecular interactions between HPV16 and miRNAs in oropharyngeal cancers. Copyright © 2018. Published by Elsevier Inc.

Prevalence of human papillomavirus infection in women in Portugal: the CLEOPATRE Portugal study.

PubMed

Pista, Angela; de Oliveira, Carlos Freire; Cunha, Maria João; Paixao, Maria Teresa; Real, Odete

2011-08-01

Human papillomavirus (HPV) is responsible for a range of diseases, including cervical cancer. The primary objectives of the CLEOPATRE Portugal study were to estimate the overall and age-stratified prevalence of cervical HPV infection and to assess HPV prevalence and type-specific distribution by cytological results among women aged 18 to 64 years, who reside in mainland Portugal. This cross-sectional population-based study recruited women aged 18 to 64 years, according to an age-stratified sampling strategy, who attended gynecology/obstetrics or sexually transmitted disease clinics across the 5 regional health administrations in mainland Portugal between 2008 and 2009. Liquid-based cytology samples were collected and analyzed centrally for HPV genotyping (clinical array HPV 2 assay) and cytology. Prevalence estimates were adjusted for age using 2007 Portuguese census data. A total of 2326 women were included in the study. The overall prevalence of HPV infection in the study was 19.4% (95% confidence interval, 17.8%-21.0%), with the highest prevalence in women aged 18 to 24 years. High-risk HPV types were detected in 76.5% of infections, of which 36.6% involved multiple types. The commonest high-risk type was HPV-16. At least 1 of the HPV types 6/11/16/18 was detected in 32.6% of infections. The HPV prevalence in normal cytology samples was 16.5%. There was a statistically significant association between high-risk infection and cytological abnormalities (P < 0.001). This is the first population-based study to quantify and describe cervical HPV infection in mainland Portugal. This study provides baseline data for future assessment of the impact of HPV vaccination programs.

Identification and functional validation of HPV-mediated hypermethylation in head and neck squamous cell carcinoma

PubMed Central

2013-01-01

Background Human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma (HNSCC) represents a distinct clinical and epidemiological condition compared with HPV-negative (HPV-) HNSCC. To test the possible involvement of epigenetic modulation by HPV in HNSCC, we conducted a genome-wide DNA-methylation analysis. Methods Using laser-capture microdissection of 42 formalin-fixed paraffin wax-embedded (FFPE) HNSCCs, we generated DNA-methylation profiles of 18 HPV+ and 14 HPV- samples, using Infinium 450 k BeadArray technology. Methylation data were validated in two sets of independent HPV+/HPV- HNSCC samples (fresh-frozen samples and cell lines) using two independent methods (Infinium 450 k and whole-genome methylated DNA immunoprecipitation sequencing (MeDIP-seq)). For the functional analysis, an HPV- HNSCC cell line was transduced with lentiviral constructs containing the two HPV oncogenes (E6 and E7), and effects on methylation were assayed using the Infinium 450 k technology. Results and discussion Unsupervised clustering over the methylation variable positions (MVPs) with greatest variation showed that samples segregated in accordance with HPV status, but also that HPV+ tumors are heterogeneous. MVPs were significantly enriched at transcriptional start sites, leading to the identification of a candidate CpG island methylator phenotype in a sub-group of the HPV+ tumors. Supervised analysis identified a strong preponderance (87%) of MVPs towards hypermethylation in HPV+ HNSCC. Meta-analysis of our HNSCC and publicly available methylation data in cervical and lung cancers confirmed the observed DNA-methylation signature to be HPV-specific and tissue-independent. Grouping of MVPs into functionally more significant differentially methylated regions identified 43 hypermethylated promoter DMRs, including for three cadherins of the Polycomb group target genes. Integration with independent expression data showed strong negative correlation, especially for the cadherin gene-family members. Combinatorial ectopic expression of the two HPV oncogenes (E6 and E7) in an HPV- HNSCC cell line partially phenocopied the hypermethylation signature seen in HPV+ HNSCC tumors, and established E6 as the main viral effector gene. Conclusions Our data establish that archival FFPE tissue is very suitable for this type of methylome analysis, and suggest that HPV modulates the HNSCC epigenome through hypermethylation of Polycomb repressive complex 2 target genes such as cadherins, which are implicated in tumor progression and metastasis. PMID:23419152

Detection of high-risk mucosal human papillomavirus DNA in human specimens by a novel and sensitive multiplex PCR method combined with DNA microarray.

PubMed

Gheit, Tarik; Tommasino, Massimo

2011-01-01

Epidemiological and functional studies have clearly demonstrated that certain types of human papillomavirus (HPV) from the genus alpha of the HPV phylogenetic tree, referred to as high-risk (HR) types, are the etiological cause of cervical cancer. Several methods for HPV detection and typing have been developed, and their importance in clinical and epidemiological studies has been well demonstrated. However, comparative studies have shown that several assays have different sensitivities for the detection of specific HPV types, particularly in the case of multiple infections. In this chapter, we describe a novel one-shot method for the detection and typing of 19 mucosal HR HPV types (types 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 70, 73, and 82). The assay combines the advantages of the multiplex PCR methods, i.e., high sensitivity and the possibility to perform multiple amplifications in a single reaction, with an array primer extension (APEX) assay. The latter method offers the benefits of Sanger dideoxy sequencing with the high-throughput potential of the microarray. Initial studies have revealed that the assay is very sensitive in detecting multiple HPV infections.

Outsmart HPV: Acceptability and short-term effects of a web-based HPV vaccination intervention for young adult gay and bisexual men.

PubMed

McRee, Annie-Laurie; Shoben, Abigail; Bauermeister, Jose A; Katz, Mira L; Paskett, Electra D; Reiter, Paul L

2018-01-10

Effective interventions to promote human papillomavirus (HPV) vaccination are needed, particularly among populations at increased risk of HPV-related disease. We developed and pilot tested a web-based intervention, Outsmart HPV, to promote HPV vaccination among young gay and bisexual men (YGBM). In 2016, we recruited a national sample (n = 150) of YGBM ages 18-25 in the United States who had not received any doses of HPV vaccine. Participants were randomized to receive either standard HPV vaccination information (control) or population-targeted, individually-tailored content (Outsmart HPV intervention). We assessed between group differences in HPV vaccination attitudes and beliefs immediately following the intervention using multiple linear regression. There were no differences in HPV vaccination attitudes, beliefs and intentions between groups at baseline. Compared to participants in the control group, intervention participants reported: greater perception that men who have sex with men are at higher risk for anal cancer relative to other men (b = 0.34); greater HPV vaccination self-efficacy (b = 0.15); and fewer perceived harms of HPV vaccine (b = -0.34) on posttest surveys (all p < .05). Overall, intervention participants reported high levels of acceptability and satisfaction with the Outsmart HPV intervention (all > 4.4 on a 5-point scale). Findings from this study provide preliminary support for a brief, tailored web-based intervention in improving HPV vaccination attitudes and beliefs among YGBM. An important next step is to determine the effects of Outsmart HPV on HPV vaccine uptake. ClinicalTrials.gov identifier NCT02835755. Copyright © 2018 Elsevier Ltd. All rights reserved.

Detection of Human Papillomavirus Type 2 Related Sequence in Oral Papilloma

PubMed Central

Yamaguchi, Taihei; Shindoh, Masanobu; Amemiya, Akira; Inoue, Nobuo; Kawamura, Masaaki; Sakaoka, Hiroshi; Inoue, Masakazu; Fujinaga, Kei

1998-01-01

Oral papilloma is a benign tumourous lesion. Part of this lesion is associated with human papillomavirus (HPV) infection. We analysed the genetical and histopathological evidence for HPV type 2 infection in three oral papillomas. Southern blot hybridization showed HPV 2a sequence in one lesion. Cells of the positive specimen appeared to contain high copy numbers of the viral DNA in an episomal state. In situ staining demonstrated virus capsid antigen in koilocytotic cells and surrounding cells in the hyperplastic epithelial layer. Two other specimens contained no HPV sequences by labeled probe of full length linear HPVs 2a, 6b, 11, 16, 18, 31 and 33 DNA under low stringency hybridization conditions. These results showed the possibility that HPV 2 plays a role in oral papilloma. PMID:9699941

Changes in global gene expression profiles induced by HPV 16 E6 oncoprotein variants in cervical carcinoma C33-A cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zacapala-Gómez, Ana Elvira, E-mail: zak_ana@yahoo.com.mx; Del Moral-Hernández, Oscar, E-mail: odelmoralh@gmail.com; Villegas-Sepúlveda, Nicolás, E-mail: nvillega@cinvestav.mx

We analyzed the effects of the expression of HPV 16 E6 oncoprotein variants (AA-a, AA-c, E-A176/G350, E-C188/G350, E-G350), and the E-Prototype in global gene expression profiles in an in vitro model. E6 gene was cloned into an expression vector fused to GFP and was transfected in C33-A cells. Affymetrix GeneChip Human Transcriptome Array 2.0 platform was used to analyze the expression of over 245,000 coding transcripts. We found that HPV16 E6 variants altered the expression of 387 different genes in comparison with E-Prototype. The altered genes are involved in cellular processes related to the development of cervical carcinoma, such asmore » adhesion, angiogenesis, apoptosis, differentiation, cell cycle, proliferation, transcription and protein translation. Our results show that polymorphic changes in HPV16 E6 natural variants are sufficient to alter the overall gene expression profile in C33-A cells, explaining in part the observed differences in oncogenic potential of HPV16 variants. - Highlights: • Amino acid changes in HPV16 E6 variants modulate the transciption of specific genes. • This is the first comparison of global gene expression profile of HPV 16 E6 variants. • Each HPV 16 E6 variant appears to have its own molecular signature.« less

Human papilloma virus prevalence, genotype distribution, and pattern of infection in Thai women.

PubMed

Suthipintawong, Cheepsumon; Siriaunkgul, Sumalee; Tungsinmunkong, Kobkul; Pientong, Chamsai; Ekalaksananan, Tipaya; Karalak, Anant; Kleebkaow, Pilaiwan; Vinyuvat, Songkhun; Triratanachat, Surang; Khunamornpong, Surapan; Chongsuwanich, Tuenjai

2011-01-01

The pattern of infection in cervical lesions with respect to HPV subtype has not been systematically studied in Thai women. The aim here was to determine HPV prevalence, genotype, and infection pattern in cervical lesions and to estimate the potential efficacy of an HPV prophylactic vaccine. Formalin-fixed paraffin-embedded cervical tissue blocks of 410 Thai patients from 8 institutes in 4 regions of Thailand (northern, southern, north-eastern, and central) were studied. The samples included 169 low grade squamous intraepithelial lesions (LSILs), 121 high grade squamous intraepithelial lesions (HSILs), and 120 squamous cell carcinomas (SCCs). HPV-DNA was amplified by PCR using consensus primers GP5+ and GP6+. The HPV genotype was then determined by reverse linear blot assay that included 37 HPV-specific 5'-amino-linked oligonucleotide probes. Patterns of infection were classified as single infection (one HPV type), double infection (two HPV types), and multiple infection (three or more HPV types). The mean age of the subjects was 42 years. The prevalence of HPV infection was 88.8%. The highest HPV prevalence was found in the southern region (97.1%) and the lowest in the central region (78.6%). HPV-DNA was detected in 84.6% of LSILs, 90.1% of HSILs, and 93.3% of SCCs. A total of 20 HPV genotypes were identified. The five most common high risk HPV were HPV16 (83.2%), HPV18 (59.3%), HPV58 (9.3%), HPV52 (4.1%), and HPV45 (3.8%). In double and multiple infection patterns, the most common genotypes were HPV16/18 (27.8%) and HPV11/16/18 (54.9%). HPV6 was found only in LSIL and never in combination with other subtypes. HPV11 was most common in LSIL. There is no difference of HPV type distribution in women from 4 regions of Thailand with prominent HPV16 and HPV18 in all cases. The bivalent and quadrivalent vaccines have the potential to prevent 48.6 % and 74.5% of cervical cancers in Thai women. The potential of cancer prevention would rise to 87.6% if other frequent HR-HPV types (HPV58, 52, and 45) were also targeted by an HPV vaccine.

High-Risk HPV, Biomarkers, and Outcome in Matched Cohorts of Head and Neck Cancer Patients Positive and Negative for HIV.

PubMed

Walline, Heather M; Carey, Thomas E; Goudsmit, Christine M; Bellile, Emily L; D'Souza, Gypsyamber; Peterson, Lisa A; McHugh, Jonathan B; Pai, Sara I; Lee, J Jack; Shin, Dong M; Ferris, Robert L

2017-02-01

In this study, high-risk HPV (hrHPV) incidence, prognostic biomarkers, and outcome were assessed in HIV-positive (case) and HIV-negative (control) patients with head and neck squamous cell cancer (HNSCC). HIV-positive cases were matched to controls by tumor site, sex, and age at cancer diagnosis. A tissue microarray (TMA) was constructed and DNA isolated from tumor tissue. MultiPlex-PCR MassArray, L1-PCR, and in situ hybridization were used to assess hrHPV. TMA sections were stained for p16ink4a, TP53, RB, CCND1, EGFR, and scored for intensity and proportion of positive tumor cells. The HNSCC cohort included 41 HIV-positive cases and 41 HIV-negative controls. Tumors from 11 of 40 (28%) cases, and 10 of 41 (24%) controls contained hrHPV. p16 expression, indicative of E7 oncogene activity, was present in 10 of 11 HPV-positive cases and 7 of 10 HPV-positive controls. Low p16 and high TP53 expression in some HPV-positive tumors suggested HPV-independent tumorigenesis. Survival did not differ in cases and controls. RB expression was significantly associated with poor survival (P = 0.01). High TP53 expression exhibited a trend for poorer survival (P = 0.12), but among cases, association with poor survival reached statistical significance (P = 0.04). The proportion of HPV-positive tumors was similar, but the heterogeneity of HPV types was higher in the HIV-positive cases than in HIV-negative controls. High RB expression predicted poor survival, and high TP53 expression was associated with poorer survival in the HIV-positive cases but not HIV-negative controls. HIV infection did not increase risk of death from HNSCC, and HPV-positive tumors continued to be associated with a significantly improved survival, independent of HIV status. Mol Cancer Res; 15(2); 179-88. ©2016 AACR. ©2016 American Association for Cancer Research.

Real-time PCR assays using internal controls for quantitation of HPV-16 and beta-globin DNA in cervicovaginal lavages.

PubMed

Lefevre, Jonas; Hankins, Catherine; Pourreaux, Karina; Voyer, Hélène; Coutlée, François

2003-12-01

High-risk human papillomavirus 16 (HPV-16) DNA viral load has been measured with real-time PCR assays by amplifying HPV-16 and a human gene. However, these assays have not used internal controls (ICs) to screen for the presence of inhibitors contained in samples. To quantitate HPV-16 DNA and cell content with real-time PCR, ICs for HPV-16 DNA and beta-globin were synthesised and used to control for inhibition. The assays were sensitive and linear over 5 logs. Good reproducibility was achieved with inter-run coefficients of variation of 23% (10(2) HPV-16 copies), 12% (10(4) HPV-16 copies), 17% (274 beta-globin DNA copies) and 7% (27,400 beta-globin DNA copies). Samples containing 56,800,000, 306,000, 18,000, and 4,070 HPV-16 copies/microg of cellular DNA were tested blindly and estimated to contain 48,800,000, 479,000, 20,300, and 6,620 HPV-16 copies/microg of DNA (mean ratio of measured to expected viral load of 1.27+/-0.32). Inhibition of amplification of HPV-16 and beta-globin ICs by six samples known to contain PCR inhibitors was variable: four inhibited both ICs while two inhibited only the HPV-16 IC. The use of internal controls with real-time PCR for HPV-16 quantitation allows to screen for the presence of inhibitors that do not affect equally primer-driven genomic amplification.

Impact of introduction of the 9-valent human papillomavirus vaccine on vaccination coverage of youth in North Carolina.

PubMed

Trogdon, Justin G; Shafer, Paul; Lindsay, Brianna; Coyne-Beasley, Tamera

2018-02-28

The objective of this study was to evaluate the impact of introduction of 9vHPV vaccine on HPV vaccination uptake (doses per capita) and initiation (≥1 doses), completion (≥3 doses) and compliance (≥3 doses within 12 months) by adolescents. We used a retrospective cohort analysis using North Carolina Immunization Registry (NCIR) data from January 2008 through October 2016. The sample included Vaccines for Children eligible adolescents aged 9 to 17 years in 2016, for whom the NCIR contains complete vaccination history. We applied an interrupted time series design to measure associations between ZIP Code Tabulation Area (ZCTA)-level HPV vaccination outcomes over time with the introduction of 9vHPV in North Carolina (NC) in July 2015. Each outcome displayed a linear upward trend over time with large seasonal spikes near August of each year, corresponding to the time when adolescents often receive other vaccines required for school entry. After accounting for these underlying trends, introduction of 9vHPV was not associated with a change in publicly funded HPV vaccination rates in NC. Our results indicate that 9vHPV substituted for 4vHPV in the first year after release in NC, but the release of 9vHPV was not associated with an overall change in HPV vaccination. Copyright © 2018 Elsevier Ltd. All rights reserved.

Epigenetics markers of metastasis and HPV-induced tumorigenesis in penile cancer.

PubMed

Feber, Andrew; Arya, Manit; de Winter, Patricia; Saqib, Muhammad; Nigam, Raj; Malone, Peter R; Tan, Wei Shen; Rodney, Simon; Lechner, Matthias; Freeman, Alex; Jameson, Charles; Muneer, Asif; Beck, Stephan; Kelly, John D

2015-03-01

Penile cancer is a rare malignancy in the developed world with just more than 1,600 new cases diagnosed in the United States per year; however, the incidence is much higher in developing countries. Although HPV is known to contribute to tumorigenesis, little is known about the genetic or epigenetic alterations defining penile cancer. Using high-density genome-wide methylation arrays, we have identified epigenetic alterations associated with penile cancer. Q-MSP was used to validate lymph node metastasis markers in 50 cases. A total of 446 head and neck squamous cell carcinoma (HNSCC) and cervical squamous cell carcinoma (CESCC) samples were used to validate HPV-associated epigenetic alterations. We defined 6,933 methylation variable positions (MVP) between normal and tumor tissue, which includes 997 hypermethylated differentially methylated regions associated with tumor supressor genes, including CDO1, AR1, and WT1. Analysis of penile cancer tumors identified a 4 gene epi-signature which accurately predicted lymph node metastasis in an independent cohort (AUC of 89%). Finally, we explored the epigenetic alterations associated with penile cancer HPV infection and defined a 30 loci lineage-independent HPV specific epi-signature which predicts HPV status and survival in independent HNSCC, CESC cohorts. Epi-signature-negative patients have a significantly worse overall survival [HNSCC P = 0.00073; 95% confidence interval (CI), 0.021-0.78; CESC P = 0.0094; HR = 3.91, 95% CI = 0.13-0.78], HPV epi-signature is a better predictor of survival than HPV status alone. These data demonstrate for the first time genome-wide epigenetic events involved in an aggressive penile cancer phenotype and define the epigenetic alterations common across multiple HPV-driven malignancies. ©2014 American Association for Cancer Research.

Epigenetics markers of metastasis and HPV induced tumourigenesis in Penile cancer

PubMed Central

Feber, Andrew; Arya, Manit; de Winter, Patricia; Saqib, Muhammad; Nigam, Raj; Malone, Peter R; Tan, Wei Shen; Rodney, Simon; Lechner, Matthias; Freeman, Alex; Jameson, Charles; Muneer, Asif; Beck, Stephan; Kelly, John D

2015-01-01

Purpose Penile cancer is a rare malignancy in the developed world, with just over 1600 new cases diagnosed in the USA per year, however, the incidence is much higher in developing countries. Although HPV is known to contribute to tumourigenesis, little is known about the genetic or epigenetic alterations defining penile cancer (PeCa). Experimental Design Using high-density genome-wide methylation arrays we have identified epigenetic alterations associated with PeCa. Q-MSP was used to validate lymph node metastasis markers in 50 cases. 446 HNSCC and CESCC (head and neck squamous cell carcinoma and cervical squamous cell carcinoma) samples were used to validate HPV associated epigenetic alterations. Results We defined 6933 methylation variable positions (MVPs) between normal and tumour tissue, which include 997 hypermethylated differentially methylated regions associated with tumour supressor genes including CDO1, AR1 and WT1. Analysis of PeCa tumours identified a 4 gene epi-signature which accurately predicted lymph node metastasis in an independent cohort (AUC of 89%). Finally, we explored the epigenetic alterations associated with PeCa HPV infection and defined a 30 loci lineage independent HPV specific epi-signature which predicts HPV status and survival in independent HNSCC, CESC cohorts. Epi-signature negative patients have a significantly worse overall survival (HNSCC p=0.00073, CI 0.021-0.78, CESC p= 0.0094, HR=3.91, 95% CI =0.13-0.78), HPV epi-signature is a better predictor of survival than HPV status alone. Conclusion These data demonstrate for the first time genome-wide epigenetic events involved in an aggressive penile cancer phenotype and define the epigenetic alterations common across multiple HPV driven malignancies. PMID:25538261

Evaluation of HPV-16 and HPV-18 specific antibody measurements in saliva collected in oral rinses and merocel® sponges.

PubMed

Parker, Katherine H; Kemp, Troy J; Pan, Yuanji; Yang, Zhen; Giuliano, Anna R; Pinto, Ligia A

2018-05-03

Current Human papillomavirus (HPV) L1 VLP vaccines protect against HPV-16 and HPV-18-associated cancers, in females and males. Although correlates of protection have not been identified, HPV-specific antibodies at sites of infection are thought to be the main mechanism of protection afforded by vaccination. Oral sampling has gained increased attention as a potential alternative to serum in monitoring immunity to vaccination and understanding local immunity in oral cancers. Serum was collected via venipuncture, and saliva was collected via oral rinses and Merocel® sponges from healthy volunteers: 16 unvaccinated females, 6 females (ages 24-41) and 6 mid-adult aged males (ages 27-45) recipients of three doses of the HPV-16/18/6/11 vaccine (Gardasil®). Mid-adult male vaccine trial participants were compared to female participants. Samples were tested for anti-HPV-16 and anti-HPV-18 immunoglobulin G levels by an L1 virus-like particle-based enzyme-linked immunosorbent assay (ELISA). All vaccinated participants had detectable serum anti-HPV-16 and anti-HPV-18 antibodies. Optimal standard concentration range and sample serial dilutions for oral rinses were determined. The standard curve was not affected by the type of solution examined. Reproducibility of HPV-16 and HPV-18 antibody titers in mouthwash (overall CV < 10%) or in Merocel® extraction buffer was robust (CV < 13%). Excellent assay linearity (R 2  > 0.9) was observed for sera spiked controls in both solutions. HPV-16 and HPV-18 specific antibodies were detectable in saliva from vaccine recipients, both in mouthwash and in Merocel® sponges but levels were several logs lower than those in serum. This study confirms the application of HPV-16 and HPV-18 ELISAs currently used in sero-epidemiological studies of immunogenicity of HPV vaccines for use with oral samples. Oral samples may be a useful resource for the detection of HPV-16 and HPV-18-specific antibodies in saliva following vaccination. Copyright © 2018 Elsevier Ltd. All rights reserved.

Human papillomavirus infection and spontaneous abortion: a case-control study performed in Mexico.

PubMed

Conde-Ferráez, Laura; Chan May, Alberto de A; Carrillo-Martínez, Jorge R; Ayora-Talavera, Guadalupe; González-Losa, María del Refugio

2013-10-01

To investigate if HPV cervical infection is associated with spontaneous abortion in a Mexican population. Case control study including 281 women from two Social Security Hospitals in Merida, Mexico. Cases were women with spontaneous abortion attending for curettage, and controls were pregnant women at term who attended for delivery. HPV molecular detection and typing of HPV 16, 18, 58 and 6/11 was performed on cervical samples, and TORCH serology IgM tests (against T. gondii, CMV, HSV) were performed on cases. Data were analyzed using Chi square, odds ratio and linear regression tests. HPV global prevalence was 19.8% (24.4% in cases and 15.2% in controls). HPV types 16 and 58 were the most frequently detected in both groups. Multiple HPV types concurrent infection were found in 31.4% of typified samples. Amongst cases 27.3% of HPV positive women reported at least one previous pregnancy loss; compared to 17.43% amongst HPV negative women. Nevertheless, HPV was not significantly associated with spontaneous or to repetitive abortion. Cases were 60.2% positive to any TORCH agent, although it was not significantly associated to referred miscarriage history. Spontaneous abortion was associated to a previous pregnancy loss and to women's age older than 35 years old. HPV infection was significantly associated to alcohol intake before pregnancy and to multiple sexual partners. HPV cervical infection was not associated with spontaneous abortion. HPV in spontaneous abortion and other adverse pregnancy outcomes merits further study. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Risk of newly detected infections and cervical abnormalities in women seropositive for naturally acquired human papillomavirus type 16/18 antibodies: analysis of the control arm of PATRICIA.

PubMed

Castellsagué, Xavier; Naud, Paulo; Chow, Song-Nan; Wheeler, Cosette M; Germar, Maria Julieta V; Lehtinen, Matti; Paavonen, Jorma; Jaisamrarn, Unnop; Garland, Suzanne M; Salmerón, Jorge; Apter, Dan; Kitchener, Henry; Teixeira, Julio C; Skinner, S Rachel; Limson, Genara; Szarewski, Anne; Romanowski, Barbara; Aoki, Fred Y; Schwarz, Tino F; Poppe, Willy A J; Bosch, F Xavier; de Carvalho, Newton S; Peters, Klaus; Tjalma, Wiebren A A; Safaeian, Mahboobeh; Raillard, Alice; Descamps, Dominique; Struyf, Frank; Dubin, Gary; Rosillon, Dominique; Baril, Laurence

2014-08-15

We examined risk of newly detected human papillomavirus (HPV) infection and cervical abnormalities in relation to HPV type 16/18 antibody levels at enrollment in PATRICIA (Papilloma Trial Against Cancer in Young Adults; NCT00122681). Using Poisson regression, we compared risk of newly detected infection and cervical abnormalities associated with HPV-16/18 between seronegative vs seropositive women (15-25 years) in the control arm (DNA negative at baseline for the corresponding HPV type [HPV-16: n = 8193; HPV-18: n = 8463]). High titers of naturally acquired HPV-16 antibodies and/or linear trend for increasing antibody levels were significantly associated with lower risk of incident and persistent infection, atypical squamous cells of undetermined significance or greater (ASCUS+), and cervical intraepithelial neoplasia grades 1/2 or greater (CIN1+, CIN2+). For HPV-18, although seropositivity was associated with lower risk of ASCUS+ and CIN1+, no association between naturally acquired antibodies and infection was demonstrated. Naturally acquired HPV-16 antibody levels of 371 (95% confidence interval [CI], 242-794), 204 (95% CI, 129-480), and 480 (95% CI, 250-5756) EU/mL were associated with 90% reduction of incident infection, 6-month persistent infection, and ASCUS+, respectively. Naturally acquired antibodies to HPV-16, and to a lesser extent HPV-18, are associated with some reduced risk of subsequent infection and cervical abnormalities associated with the same HPV type. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Risk of Newly Detected Infections and Cervical Abnormalities in Women Seropositive for Naturally Acquired Human Papillomavirus Type 16/18 Antibodies: Analysis of the Control Arm of PATRICIA

PubMed Central

Castellsagué, Xavier; Naud, Paulo; Chow, Song-Nan; Wheeler, Cosette M.; Germar, Maria Julieta V.; Lehtinen, Matti; Paavonen, Jorma; Jaisamrarn, Unnop; Garland, Suzanne M.; Salmerón, Jorge; Apter, Dan; Kitchener, Henry; Teixeira, Julio C.; Skinner, S. Rachel; Limson, Genara; Szarewski, Anne; Romanowski, Barbara; Aoki, Fred Y.; Schwarz, Tino F.; Poppe, Willy A. J.; Bosch, F. Xavier; de Carvalho, Newton S.; Peters, Klaus; Tjalma, Wiebren A. A.; Safaeian, Mahboobeh; Raillard, Alice; Descamps, Dominique; Struyf, Frank; Dubin, Gary; Rosillon, Dominique; Baril, Laurence

2014-01-01

Background. We examined risk of newly detected human papillomavirus (HPV) infection and cervical abnormalities in relation to HPV type 16/18 antibody levels at enrollment in PATRICIA (Papilloma Trial Against Cancer in Young Adults; NCT00122681). Methods. Using Poisson regression, we compared risk of newly detected infection and cervical abnormalities associated with HPV-16/18 between seronegative vs seropositive women (15–25 years) in the control arm (DNA negative at baseline for the corresponding HPV type [HPV-16: n = 8193; HPV-18: n = 8463]). Results. High titers of naturally acquired HPV-16 antibodies and/or linear trend for increasing antibody levels were significantly associated with lower risk of incident and persistent infection, atypical squamous cells of undetermined significance or greater (ASCUS+), and cervical intraepithelial neoplasia grades 1/2 or greater (CIN1+, CIN2+). For HPV-18, although seropositivity was associated with lower risk of ASCUS+ and CIN1+, no association between naturally acquired antibodies and infection was demonstrated. Naturally acquired HPV-16 antibody levels of 371 (95% confidence interval [CI], 242–794), 204 (95% CI, 129–480), and 480 (95% CI, 250–5756) EU/mL were associated with 90% reduction of incident infection, 6-month persistent infection, and ASCUS+, respectively. Conclusions. Naturally acquired antibodies to HPV-16, and to a lesser extent HPV-18, are associated with some reduced risk of subsequent infection and cervical abnormalities associated with the same HPV type. PMID:24610876

Motivational and contextual determinants of HPV-vaccination uptake: A longitudinal study among mothers of girls invited for the HPV-vaccination.

PubMed

Pot, Mirjam; van Keulen, Hilde M; Ruiter, Robert A C; Eekhout, Iris; Mollema, Liesbeth; Paulussen, Theo W G M

2017-07-01

In the Netherlands, HPV-vaccination uptake among 12-year-old girls remains to be lower (61% in 2016) than expected. The present study is about 1) replicating the extent to which social-psychological determinants found in earlier cross-sectional studies explain HPV-vaccination intention, and 2) testing whether HPV-vaccination intention, as well as other social-psychological determinants, are good predictors of future HPV-vaccination uptake in a longitudinal design. A random sample of mothers of girls invited for the vaccination in 2015 was drawn from the Dutch vaccination register (Praeventis) (N=36,000) and from three online panels (N=2483). Two months prior to the vaccination of girls, their mothers were requested to complete a web-based questionnaire by letter (Praeventis sample) or by e-mail (panel samples). HPV-vaccination uptake was derived from Praeventis. Backward linear and logistic regression analyses were conducted to examine most dominant predictors of HPV-vaccination intention and uptake, respectively. The total sample used for data analyses consisted of 8062 mothers. Response rates were 18% for the Praeventis sample and 47% for the panel samples. HPV-vaccination intention was best explained by attitude, beliefs, subjective norms, habit, and perceived relative effectiveness of the vaccination; they explained 83% of the variance in HPV-vaccination intention. Intention appeared to be the only stable predictor of HPV-vaccination uptake and explained 43% of the variance in HPV-vaccination uptake. These results confirm what was found by earlier cross-sectional studies, and provide strong leads for selecting relevant targets in the planning of future communication strategies aiming to improve HPV-vaccination uptake. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Sociodemographic Factors Associated With Knowledge and Risk Perception of Human Papillomavirus and Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma Among a Predominantly Black Population.

PubMed

Osazuwa-Peters, Nosayaba; Adjei Boakye, Eric; Chen, Betty Y; Clancy, Jennifer; Vallot, Patrice L; Su, Jonathan L; Beck, Geoffrey E; Varvares, Mark A

2017-02-01

The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is increasing in the United States and may be underestimated among black individuals. Characterizing the current knowledge level among black individuals is critical to developing interventions to increase awareness. To describe the sociodemographic correlates of knowledge and risk perception of HPV and HPV-associated OPSCC among a predominantly black population. A cross-sectional survey was conducted at a drag racing event on September 12 and 13, 2015, in Madison, Illinois. The setting was a community-based oral head and neck cancer screening and education initiative. Participants were 301 drag race attendees 18 years or older who were conveniently sampled from attendees at an annual drag racing event predominantly patronized by black individuals. The primary outcome was knowledge and risk perception of HPV and HPV-associated OPSCC. An electronic-based questionnaire elicited sociodemographic information and contained oral cancer knowledge and risk perception items, which were combined to form knowledge and risk perception scores. Multivariable linear regression analysis assessed estimates of knowledge and risk perception of HPV and HPV-associated OPSCC. Of the 301 participants (111 female and 190 male) completing the questionnaire, 194 (64.5%) were black. Overall, respondents ranged in age from 18 to 78 years, with a mean (SD) age of 48.0 (13.0) years. The mean (SD) knowledge score was 5.7 (4.6) of 15, and the mean (SD) risk perception score was 2.2 (1.4) of 6. Using multivariable linear regression, we found that, for every 1-year increase in age, knowledge of HPV-associated OPSCC decreased by 5.0% and was worse in men (β = -1.26; 95% CI, -2.33 to -0.18), black vs white individuals (β = -1.29; 95% CI, -2.35 to -0.23), and those with a high school diploma or less vs college graduates (β = -3.23; 95% CI, -4.67 to -1.80). Black individuals also had lower perceived risk of developing HPV-associated OPSCC (β = -0.36; 95% CI, -0.69 to -0.02) compared with white individuals, and participants with a high school diploma or less had lower perceived risk of developing HPV-associated OPSCC compared with those with a college degree or higher (β = -0.59; 95% CI, -1.04 to -0.14). Age and sex were independent correlates of knowledge of HPV-associated OPSCC, while race and education level were correlates of both knowledge and risk perception of HPV-associated OPSCC. These findings should inform future interventions targeted at increasing knowledge of HPV-associated OPSCC in black communities.

Human papilloma virus genotypes in women from Nayarit, Mexico, with squamous intraepithelial lesions and cervical cancer.

PubMed

Ortega-Cervantes, Laura; Aguilar-Lemarroy, Adriana; Rojas-García, Aurora Elizabeth; Barrón-Vivanco, Briscia Socorro; Vallejo-Ruiz, Verónica; León, David Cantú-De; Hernández, Yael Yvette Bernal; Jáuregui-Martínez, Armando; Medina-Díaz, Irma Martha

2016-07-01

In Mexico cervical cancer (CC) is the most common cause of death from neoplasia in women. Study aimed to analyze the current distribution of Human papillomavirus (HPV) types in women from Nayarit, Mexico, with Squamous intraepithelial lesions (SIL) and Cervical cancer (CC). Between January 2011 and July 2013, cervical samples were collected from female residents of the Mexican state of Nayarit and were analyzed by means of a LINEAR ARRAY® HPV genotyping test. Data analyses were performed using Stata ver. 8.0 statistical software. Of the samples analyzed, 91.2%, HPV DNA was detected. Of these positive samples, 82% were High-risk (HR) viral types. The most prevalent HPV genotypes identified were 16, 58, 31, 18, and 70. Forty two percent of participants had a single infection, while 23 and 26% of participants were infected with two or more HPV genotypes, respectively. HPV 16 was the most prevalent genotype identified and was frequently present as a co-infection with HPV types 18, 51, 52, 59, 66, or 70. Women <20 years of age were most often infected with HPV, and the HPV Quadrivalent vaccine (types 16, 18, 6, and 11), currently available in Mexico, no confers protection against a subset of the HPV genotypes identified in the present study (58, 31, 70, and 35). Thus, it is important evaluate the geographical distribution of specific HPV genotypes in all health of center across Mexico in order to implement a successful vaccination program and to diagnose CC in its early stages.

Human papilloma virus genotypes in women from Nayarit, Mexico, with squamous intraepithelial lesions and cervical cancer

PubMed Central

Ortega-Cervantes, Laura; Aguilar-Lemarroy, Adriana; Rojas-García, Aurora Elizabeth; Barrón-Vivanco, Briscia Socorro; Vallejo-Ruiz, Verónica; León, David Cantú-De; Hernández, Yael Yvette Bernal; Jáuregui-Martínez, Armando; Medina-Díaz, Irma Martha

2016-01-01

Objective In Mexico cervical cancer (CC) is the most common cause of death from neoplasia in women. Study aimed to analyze the current distribution of Human papillomavirus (HPV) types in women from Nayarit, Mexico, with Squamous intraepithelial lesions (SIL) and Cervical cancer (CC). Methodology Between January 2011 and July 2013, cervical samples were collected from female residents of the Mexican state of Nayarit and were analyzed by means of a LINEAR ARRAY® HPV genotyping test. Data analyses were performed using Stata ver. 8.0 statistical software. Results Of the samples analyzed, 91.2%, HPV DNA was detected. Of these positive samples, 82% were High-risk (HR) viral types. The most prevalent HPV genotypes identified were 16, 58, 31, 18, and 70. Forty two percent of participants had a single infection, while 23 and 26% of participants were infected with two or more HPV genotypes, respectively. HPV 16 was the most prevalent genotype identified and was frequently present as a co-infection with HPV types 18, 51, 52, 59, 66, or 70. Conclusion Women <20 years of age were most often infected with HPV, and the HPV Quadrivalent vaccine (types 16, 18, 6, and 11), currently available in Mexico, no confers protection against a subset of the HPV genotypes identified in the present study (58, 31, 70, and 35). Thus, it is important evaluate the geographical distribution of specific HPV genotypes in all health of center across Mexico in order to implement a successful vaccination program and to diagnose CC in its early stages. PMID:27610056

Integration of HPV6 and Downregulation of AKR1C3 Expression Mark Malignant Transformation in a Patient with Juvenile-Onset Laryngeal Papillomatosis

PubMed Central

Kolligs, Jutta; Vent, Julia; Stenner, Markus; Wieland, Ulrike; Silling, Steffi; Drebber, Uta; Speel, Ernst-Jan M.; Klussmann, Jens Peter

2013-01-01

Juvenile-onset recurrent respiratory papillomatosis (RRP) is associated with low risk human papillomavirus (HPV) types 6 and 11. Malignant transformation has been reported solely for HPV11-associated RRP in 2–4% of all RRP-cases, but not for HPV6. The molecular mechanisms in the carcinogenesis of low risk HPV-associated cancers are to date unknown. We report of a female patient, who presented with a laryngeal carcinoma at the age of 24 years. She had a history of juvenile-onset RRP with an onset at the age of three and subsequently several hundred surgical interventions due to multiple recurrences of RRP. Polymerase chain reaction (PCR) or bead-based hybridization followed by direct sequencing identified HPV6 in tissue sections of previous papilloma and the carcinoma. P16INK4A, p53 and pRb immunostainings were negative in all lesions. HPV6 specific fluorescence in situ hybridization (FISH) revealed nuclear staining suggesting episomal virus in the papilloma and a single integration site in the carcinoma. Integration-specific amplification of papillomavirus oncogene transcripts PCR (APOT-PCR) showed integration in the aldo-keto reductase 1C3 gene (AKR1C3) on chromosome 10p15.1. ArrayCGH detected loss of the other gene copy as part of a deletion at 10p14-p15.2. Western blot analysis and immunohistochemistry of the protein AKR1C3 showed a marked reduction of its expression in the carcinoma. In conclusion, we identified a novel molecular mechanism underlying a first case of HPV6-associated laryngeal carcinoma in juvenile-onset RRP, i.e. that HPV6 integration in the AKR1C3 gene resulted in loss of its expression. Alterations of AKR1C gene expression have previously been implicated in the tumorigenesis of other (HPV-related) malignancies. PMID:23437342

Age of child, more than HPV type, is associated with clinical course in recurrent respiratory papillomatosis.

PubMed

Buchinsky, Farrel J; Donfack, Joseph; Derkay, Craig S; Choi, Sukgi S; Conley, Stephen F; Myer, Charles M; McClay, John E; Campisi, Paolo; Wiatrak, Brian J; Sobol, Steven E; Schweinfurth, John M; Tsuji, Domingos H; Hu, Fen Z; Rockette, Howard E; Ehrlich, Garth D; Post, J Christopher

2008-05-28

RRP is a devastating disease in which papillomas in the airway cause hoarseness and breathing difficulty. The disease is caused by human papillomavirus (HPV) 6 or 11 and is very variable. Patients undergo multiple surgeries to maintain a patent airway and in order to communicate vocally. Several small studies have been published in which most have noted that HPV 11 is associated with a more aggressive course. Papilloma biopsies were taken from patients undergoing surgical treatment of RRP and were subjected to HPV typing. 118 patients with juvenile-onset RRP with at least 1 year of clinical data and infected with a single HPV type were analyzed. HPV 11 was encountered in 40% of the patients. By our definition, most of the patients in the sample (81%) had run an aggressive course. The odds of a patient with HPV 11 running an aggressive course were 3.9 times higher than that of patients with HPV 6 (Fisher's exact p = 0.017). However, clinical course was more closely associated with age of the patient (at diagnosis and at the time of the current surgery) than with HPV type. Patients with HPV 11 were diagnosed at a younger age (2.4y) than were those with HPV 6 (3.4y) (p = 0.014). Both by multiple linear regression and by multiple logistic regression HPV type was only weakly associated with metrics of disease course when simultaneously accounting for age. CONCLUSIONS/SIGNIFICANCE ABSTRACT: The course of RRP is variable and a quarter of the variability can be accounted for by the age of the patient. HPV 11 is more closely associated with a younger age at diagnosis than it is associated with an aggressive clinical course. These data suggest that there are factors other than HPV type and age of the patient that determine disease course.

DNA Damage Repair Genes Controlling Human Papillomavirus (HPV) Episome Levels under Conditions of Stability and Extreme Instability

PubMed Central

Edwards, Terri G.; Vidmar, Thomas J.; Koeller, Kevin; Bashkin, James K.; Fisher, Chris

2013-01-01

DNA damage response (DDR) genes and pathways controlling the stability of HPV episomal DNA are reported here. We set out to understand the mechanism by which a DNA-binding, N-methylpyrrole-imidazole hairpin polyamide (PA25) acts to cause the dramatic loss of HPV DNA from cells. Southern blots revealed that PA25 alters HPV episomes within 5 hours of treatment. Gene expression arrays identified numerous DDR genes that were specifically altered in HPV16 episome-containing cells (W12E) by PA25, but not in HPV-negative (C33A) cells or in cells with integrated HPV16 (SiHa). A siRNA screen of 240 DDR genes was then conducted to identify enhancers and repressors of PA25 activity. Serendipitously, the screen also identified many novel genes, such as TDP1 and TDP2, regulating normal HPV episome stability. MRN and 9-1-1 complexes emerged as important for PA25-mediated episome destruction and were selected for follow-up studies. Mre11, along with other homologous recombination and dsDNA break repair genes, was among the highly significant PA25 repressors. The Mre11 inhibitor Mirin was found to sensitize HPV episomes to PA25 resulting in a ∼5-fold reduction of the PA25 IC50. A novel assay that couples end-labeling of DNA to Q-PCR showed that PA25 causes strand breaks within HPV DNA, and that Mirin greatly enhances this activity. The 9-1-1 complex member Rad9, a representative PA25 enhancer, was transiently phosphorylated in response to PA25 treatment suggesting that it has a role in detecting and signaling episome damage by PA25 to the cell. These results establish that DNA-targeted compounds enter cells and specifically target the HPV episome. This action leads to the activation of numerous DDR pathways and the massive elimination of episomal DNA from cells. Our findings demonstrate that viral episomes can be targeted for elimination from cells by minor groove binding agents, and implicate DDR pathways as important mediators of this process. PMID:24098381

CITRUS, cervical cancer screening trial by randomization of HPV testing intervention for upcoming screening: Design, methods and baseline data of 18,471 women.

PubMed

Morisada, Tohru; Teramoto, Katsuhiro; Takano, Hirokuni; Sakamoto, Ikuko; Nishio, Hiroshi; Iwata, Takashi; Hashi, Akihiko; Katoh, Ryohei; Okamoto, Aikou; Sasaki, Hiroshi; Nakatani, Eiji; Teramukai, Satoshi; Aoki, Daisuke

2017-10-01

To assess the efficacy of screening with concurrent liquid-based cytology and human papillomavirus (HPV) testing for primary cervical cancer screening, we initiated a randomized trial entitled CervIcal cancer screening Trial by Randomization of HPV testing intervention for Upcoming Screening (CITRUS). Between June 2013 and March 2015, women aged 30-64 years of age who participated in a regular cervical cancer screening program (every 2 years) were invited to enrollment of our study. After giving their informed consent, 18,402 women were randomly assigned to liquid-based cytology as the control group (n=9145) or to HPV DNA testing with liquid-based cytology as the intervention group (n=9257). We subsequently compared the incidence rate of cervical intraepithelial neoplasia (CIN), the rate of false positive tests and the rate of overdiagnosis, as well as assessing the risks and benefits of receiving screening for women in both groups. The primary outcome of our study was the incidence of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) during the study period of around 6 years. In the control group, 97.9% of women were NILM, and 2.06% ASC-US or worse (ASC-US+). In the intervention group, 87.13% of women were NILM/HPV negative, 0.72% ASC-US/HPV negative, 10.34% NILM/HPV positive, 0.69% ASC-US/HPV positive, 0.90% worse than ASC-US/either HPV. Positive HPV testing was not linearly related to age in our study. Insights from CITRUS will provide future prospects for cervical cancer screening focused on the use of HPV testing in Japan. NCT01895517, UMIN000010843, TRIUC1312. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human Papillomavirus Type 18 E6 and E7 Genes Integrate into Human Hepatoma Derived Cell Line Hep G2

PubMed Central

Ma, Tianzhong; Su, Zhongjing; Chen, Ling; Liu, Shuyan; Zhu, Ningxia; Wen, Lifeng; Yuan, Yan; Lv, Leili; Chen, Xiancai; Huang, Jianmin; Chen, Haibin

2012-01-01

Background and Objectives Human papillomaviruses have been linked causally to some human cancers such as cervical carcinoma, but there is very little research addressing the effect of HPV infection on human liver cells. We chose the human hepatoma derived cell line Hep G2 to investigate whether HPV gene integration took place in liver cells as well. Methods We applied PCR to detect the possible integration of HPV genes in Hep G2 cells. We also investigated the expression of the integrated E6 and E7 genes by using RT-PCR and Western blotting. Then, we silenced E6 and E7 expression and checked the cell proliferation and apoptosis in Hep G2 cells. Furthermore, we analyzed the potential genes involved in cell cycle and apoptosis regulatory pathways. Finally, we used in situ hybridization to detect HPV 16/18 in hepatocellular carcinoma samples. Results Hep G2 cell line contains integrated HPV 18 DNA, leading to the expression of the E6 and E7 oncogenic proteins. Knockdown of the E7 and E6 genes expression reduced cell proliferation, caused the cell cycle arrest at the S phase, and increased apoptosis. The human cell cycle and apoptosis real-time PCR arrays analysis demonstrated E6 and E7-mediated regulation of some genes such as Cyclin H, UBA1, E2F4, p53, p107, FASLG, NOL3 and CASP14. HPV16/18 was found in only 9% (9/100) of patients with hepatocellular carcinoma. Conclusion Our investigations showed that HPV 18 E6 and E7 genes can be integrated into the Hep G2, and we observed a low prevalence of HPV 16/18 in hepatocellular carcinoma samples. However, the precise risk of HPV as causative agent of hepatocellular carcinoma needs further study. PMID:22655088

Development and Psychometric Evaluation of the HPV Clinical Trial Survey for Parents (CTSP-HPV) Using Traditional Survey Development Methods and Community Engagement Principles.

PubMed

Cunningham, Jennifer; Wallston, Kenneth A; Wilkins, Consuelo H; Hull, Pamela C; Miller, Stephania T

2015-12-01

This study describes the development and psychometric evaluation of HPV Clinical Trial Survey for Parents with Children Aged 9 to 15 (CTSP-HPV) using traditional instrument development methods and community engagement principles. An expert panel and parental input informed survey content and parents recommended study design changes (e.g., flyer wording). A convenience sample of 256 parents completed the final survey measuring parental willingness to consent to HPV clinical trial (CT) participation and other factors hypothesized to influence willingness (e.g., HPV vaccine benefits). Cronbach's a, Spearman correlations, and multiple linear regression were used to estimate internal consistency, convergent and discriminant validity, and predictively validity, respectively. Internal reliability was confirmed for all scales (a ≥ 0.70.). Parental willingness was positively associated (p < 0.05) with trust in medical researchers, adolescent CT knowledge, HPV vaccine benefits, advantages of adolescent CTs (r range 0.33-0.42), supporting convergent validity. Moderate discriminant construct validity was also demonstrated. Regression results indicate reasonable predictive validity with the six scales accounting for 31% of the variance in parents' willingness. This instrument can inform interventions based on factors that influence parental willingness, which may lead to the eventual increase in trial participation. Further psychometric testing is warranted. © 2015 Wiley Periodicals, Inc.

High-Risk Human Papillomavirus Is Associated with HIV Acquisition among South African Female Sex Workers

PubMed Central

Auvert, Bertran; Marais, Dianne; Lissouba, Pascale; Zarca, Kevin; Ramjee, Gita; Williamson, Anna-Lise

2011-01-01

Background. Mounting evidence suggests an association between human papillomavirus (HPV) and HIV acquisition. This study aimed to explore this association among South African female sex workers (FSWs). Methods. We used data from 88 HIV-negative FSWs who participated in a vaginal gel (COL-1492) trial. Cervicovaginal rinse samples, obtained before HIV-seroconversion, were genotyped into high-risk (HR-) and low-risk (LR-) HPV. HIV-adjusted hazard ratios (aHRs) and 95% confidence intervals (CI) were estimated using Cox survival analysis. Results. HR- and LR-HPV prevalences were 70.5% (95% CI : 60.5–79.2) and 60.2% (95% CI : 49.9–70.0), respectively. Twenty-five women HIV seroconverted. Controlling for background characteristics and other sexually transmitted infections, HIV aHR increased by a factor of 1.7 (95% CI : 1.01–2.7, P linear trend = 0.045) for an increase of one unit of the number of HR-HPV genotypes. Conclusions. HIV seroconversion among FSWs is associated with genital HR-HPV infection. Further investigation is warranted, including testing the possible protective effect of available HPV vaccines on HIV acquisition. PMID:21804752

Short-term Natural History of High-Risk Human Papillomavirus Infection in Mid-Adult Women Sampled Monthly (Short title: Short-term HPV Natural History in Mid-Adult Women)

PubMed Central

Fu, Tsung-chieh (Jane); Xi, Long Fu; Hulbert, Ayaka; Hughes, James P.; Feng, Qinghua; Schwartz, Stephen M.; Hawes, Stephen E.; Koutsky, Laura A.; Winer, Rachel L.

2015-01-01

Characterizing short-term HPV detection patterns and viral load may inform HPV natural history in mid-adult women. From 2011–2012, we recruited women aged 30–50 years. Women submitted monthly self-collected vaginal samples for high-risk HPV DNA testing for 6 months. Positive samples were tested for type-specific HPV DNA load by real-time PCR. HPV type-adjusted linear and Poisson regression assessed factors associated with 1) viral load at initial HPV detection and 2) repeat type-specific HPV detection. One-hundred thirty-nine women (36% of 387 women with ≥4 samples) contributed 243 type-specific HR HPV infections during the study; 54% of infections were prevalent and 46% were incident. Incident (versus prevalent) detection and past pregnancy were associated with lower viral load, whereas current smoking was associated with higher viral load. In multivariate analysis, current smoking was associated with a 40% (95%CI:5%–87%) increase in the proportion of samples that were repeatedly positive for the same HPV type, whereas incident (versus prevalent) detection status and past pregnancy were each associated with a reduction in the proportion of samples repeatedly positive (55%,95%CI:38%–67% and 26%,95%CI:10%–39%, respectively). In a separate multivariate model, each log10 increase in viral load was associated with a 10% (95%CI:4%–16%) increase in the proportion of samples repeatedly positive. Factors associated with repeat HPV detection were similar to those observed in longer-term studies, suggesting that short-term repeat detection may relate to long-term persistence. The negative associations between incident HPV detection and both viral load and repeat detection suggest that reactivation or intermittent persistence was more common than new acquisition. PMID:25976733

Efficacy of pulsed dye laser treatment for common warts is not influenced by the causative HPV type: a prospective study.

PubMed

Fichman, Yoseph; Levi, Assi; Hodak, Emmilia; Halachmi, Shlomit; Mazor, Sigal; Wolf, Dana; Caplan, Orit; Lapidoth, Moshe

2018-05-01

Verruca vulgaris (VV) is a prevalent skin condition caused by various subtypes of human papilloma virus (HPV). The most common causes of non-genital lesions are HPV types 2 and 4, and to a lesser extent types 1, 3, 26, 29, and 57. Although numerous therapeutic modalities exist, none is universally effective or without adverse events (AE). Pulsed dye laser (PDL) is a favorable option due to its observed efficacy and relatively low AE rate. However, it is not known which verrucae are most likely to respond to PDL, or whether the causative viral subtype influences this response. The objective of this prospective blinded study was to assess whether the HPV subtype was predictive of response to PDL. For that matter, 26 verrucae from 26 immunocompetent patients were biopsied prior to treatment by PDL. HPV coding sequences were isolated and genotyped using PCR analysis. Patients were treated by PDL (595 nm wavelength, 5 mm spot size, 1.5 ms pulse duration, 12 J/cm 2 fluence) once a month for up to 6 months, and clinical response was assessed. Binary logistic regression analysis and linear logistic regression analysis were used in order to evaluate statistical significance. Different types of HPV were identified in 22 of 26 tissue samples. Response to treatment did not correlate with HPV type, age, or gender. As no association between HPV type and response to PDL therapy could be established, it is therefore equally effective for all HPV types and remains a favorable treatment option for all VV.

Genetic Variants in TAP Are Associated with High-Grade Cervical Neoplasia

PubMed Central

Einstein, Mark H.; Leanza, Suzanne; Chiu, Lydia G.; Schlecht, Nicolas F.; Goldberg, Gary L.; Steinberg, Bettie M.; Burk, Robert D.

2018-01-01

Purpose The transporter associated with antigen processing (TAP) is essential in assembling MHC-I proteins. Human papillomavirus (HPV) evades immune recognition by decreasing class I MHC cell surface expression through down-regulation of TAP1 levels. Consistent with heterogeneity in MHC expression is the individual variability in clearing detectable HPV infections. Genetic polymorphisms in TAP genes may affect protein structure, function, and the ability to clear HPV infection. Experimental Design Case-control study of women with cervical intraepithelial neoplasia (CIN) II or III (n = 114) and women without high-grade CIN (n = 366). Five nonsynonymous single nucleotide polymorphisms (SNP) in TAP1 and TAP2 were genotyped using DNA collected in cervicovaginal lavage samples using microsphere array technology (Luminex ×MAP). HPV typing was done using a PCR-based system with MY09/MY11 primers. TAP1 and TAP2 SNPs were validated by direct sequencing. Results Differences in allele distribution between women with high-grade cervical neoplasia and women without was seen for TAP1 I333V (P = 0.02) and TAP1 D637G (p = 0.01).The odds ratios (OR) for CIN III were significantly lower among carriers of the TAP1 I333V polymorphism (OR, 0.28; 95% confidence interval, 0.1-0.8), and TAP1 D637G polymorphism (OR, 0.27; 95% confidence interval, 0.1-0.7). These associations remained significant even after restricting the evaluation to women who were positive for high-risk HPV types. Conclusions In addition to the down-regulation of MHC-1 by oncogenic HPV, HPV pathogenesis might be facilitated by polymorphisms in the TAP proteins. Identifying TAP polymorphisms may potentially be used to identify women less susceptible to progression to high-grade CIN and cervical cancer. PMID:19188174

Lab-on-chip components for molecular detection

NASA Astrophysics Data System (ADS)

Adam, Tijjani; Dhahi, Th S.; Mohammed, Mohammed; Hashim, U.; Noriman, N. Z.; Dahham, Omar S.

2017-09-01

We successfully fabricated Lab on chip components and integrated for possible use in biomedical application. The sensor was fabricated by using conventional photolithography method integrated with PDMS micro channels for smooth delivery of sample to the sensing domain. The sensor was silanized and aminated with 3-Aminopropyl triethoxysilane (APTES) to functionalize the surface with biomolecules and create molecular binding chemistry. The resulting Si-O-Si- components were functionalized with oligonucleotides probe of HPV, which interacted with the single stranded HPV DNA target to create a field across on the device. The fabrication, immobilization and hybridization processes were characterized with current voltage (I-V) characterization (KEITHLEY, 6487). The sensor show selectivity for the HPV DNA target in a linear range from concentration 0.1 nM to 1 µM. This strategy presented a simple, rapid and sensitive platform for HPV detection and would become a powerful tool for pathogenic microorganisms screening in clinical diagnosis.

Antagonist-mediated down-regulation of toll-like receptors increases the prevalence of human papillomavirus infection in systemic lupus erythematosus

PubMed Central

2012-01-01

Introduction Prevalence of an abnormal Papanicolaou smear was significantly increased in lupus patients in cross-sectional studies, associated with a higher prevalence of high-risk human papillomavirus (HPV) infection. The nucleic acid-specific Toll-like receptors (TLRs) locate at the endolysosomal compartments and trigger the induction of cytokines for the innate immune response. This study evaluated whether abnormal host innate immune response in lupus patients may enhance HPV persistence. Methods Protein levels of TLRs 3, 7, 8 and 9 in cervical epithelial cells of lupus patients and controls with or without HPV infection were assessed using flow cytometry. Characteristics associated with the differential expression of TLRs in systemic lupus erythematosus (SLE) were elucidated. The effect and interferon-stimulated genes (ISGs) (ISG15 and Mx-1) gene expressions were then measured in oncogenic HeLa (HPV18), CaSki (HPV) and C33A (HPV negative) cell lines using flow cytometry and quantitative real-time PCR. Ex vivo productions of cytokines and interferon-gamma (IFN-γ) upon TLR ligands stimulations were subsequently measured using cytometric bead array and ELISA. Results For subjects with HPV infection, levels of TLR3 and TLR7 were significantly lower in lupus patients compared with controls. Significantly decreased TLRs 7, 8 and 9 levels were observed in HPV-negative SLE compared to healthy controls. For SLE with and without HPV infection, TLR7 and 9 levels were significantly lower in infected SLE than those in HPV-negative patients. Independent explanatory variables associated with down-regulation of TLR7 level included HPV infection and a higher cumulative dose of prednisolone; while a higher cumulative dose of hydroxychloroquine and HPV infection were associated with down-regulation of TLR9 level. In cervical cell lines, TLRs 3, 7, 8, 9 protein levels and antiviral ISG15 and Mx-1 gene expressions were inhibited in two oncogenic HPV types. Functional data showed that the induction of pro-inflammatory cytokines by TLR ligands (R837, ssRNA and ODN2395) was greatly impaired in CaSki and HeLa than C33A cells. Conclusions In conclusion, prednisolone and TLR antagonist (hydroxychloroquine) may down-regulate protein levels of TLR7 and TLR9 in lupus patients, thereby decreasing the innate immune response against HPV infection. Upon infection, HPV further down-regulate TLR7 and 9 levels for viral persistence. Furthermore, reduction of nucleic acid-sensing TLRs 7, 8 and 9 in carcinogenic HPVs ensures that the expression of inducible pro-inflammatory cytokines is minimized to prevent the expression of antiviral ISGs (ISG15 and Mx-1) on a biologically relevant antiviral response. PMID:22513098

Development and Psychometric Evaluation of the HPV Clinical Trial Survey for Parents (CTSP‐HPV) Using Traditional Survey Development Methods and Community Engagement Principles

PubMed Central

Wallston, Kenneth A.; Wilkins, Consuelo H.; Hull, Pamela C.; Miller, Stephania T.

2015-01-01

Abstract Objective This study describes the development and psychometric evaluation of HPV Clinical Trial Survey for Parents with Children Aged 9 to 15 (CTSP‐HPV) using traditional instrument development methods and community engagement principles. Methods An expert panel and parental input informed survey content and parents recommended study design changes (e.g., flyer wording). A convenience sample of 256 parents completed the final survey measuring parental willingness to consent to HPV clinical trial (CT) participation and other factors hypothesized to influence willingness (e.g., HPV vaccine benefits). Cronbach's a, Spearman correlations, and multiple linear regression were used to estimate internal consistency, convergent and discriminant validity, and predictively validity, respectively. Results Internal reliability was confirmed for all scales (a ≥ 0.70.). Parental willingness was positively associated (p < 0.05) with trust in medical researchers, adolescent CT knowledge, HPV vaccine benefits, advantages of adolescent CTs (r range 0.33–0.42), supporting convergent validity. Moderate discriminant construct validity was also demonstrated. Regression results indicate reasonable predictive validity with the six scales accounting for 31% of the variance in parents’ willingness. Conclusions This instrument can inform interventions based on factors that influence parental willingness, which may lead to the eventual increase in trial participation. Further psychometric testing is warranted. PMID:26530324

Primary Care Physicians' Adherence to Guidelines and Their Likelihood to Prescribe the Human Papillomavirus Vaccine for 11- and 12-Year-Old Girls.

PubMed

Kulczycki, Andrzej; Qu, Haiyan; Shewchuk, Richard

2016-01-01

Inadequate physician adherence to guidelines has received scant attention as a possible cause of suboptimal human papillomavirus (HPV) vaccination rates. We assessed the extent to which primary care physicians (PCPs) adhere to clinical guidelines and their reported intentions to prescribe HPV vaccine to females in the targeted age group, and how this is influenced by perceptions of guideline clarity and other factors. We surveyed 301 PCPs to explore their sociodemographic and practice-related characteristics, beliefs, professional norms, and perceived barriers to administer HPV vaccine. Logistic regression predicted the likelihood to prescribe HPV vaccine to 11- and 12-year-old girls on an array of variables hypothesized to influence physicians' recommendations. Only 67% of PCPs reported being likely to prescribe HPV vaccine to 11- and 12-year-old patients. PCPs were more likely to prescribe vaccine to 11- and 12-year-old girls if they believed HPV vaccine guidelines were clear (odds ratio [OR], 1.85; 95% CI, 1.03-3.35), agreed with a mandate requirement (OR, 2.39; 95% CI, 1.01-5.61), felt comfortable discussing HPV vaccination with early adolescent girls (OR, 5.10; 95% CI, 2.75-9.45), and had at least 25% of their patients using public assistance to pay for their clinic visits (OR, 3.82; 95% CI, 1.91-7.34). Practice specialty (family physicians or pediatricians) and region were not significant predictors. PCPs exhibit moderate levels of adherence to professional guidelines regarding HPV vaccination. Potential public health benefits will not be realized without stronger efforts to improve the rates at which PCPs administer the vaccine, particularly to 11- and 12-year-olds for whom it is preferentially recommended. Copyright © 2016 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Highly Sensitive Detection and Genotyping of HPV by PCR Multiplex and Luminex Technology in a Cohort of Colombian Women with Abnormal Cytology

PubMed Central

García, Dabeiba A; Cid-Arregui, Angel; Schmitt, Markus; Castillo, Marcos; Briceño, Ignacio; Aristizábal, Fabio A

2011-01-01

Cancer of the uterine cervix (CC) is the second most common cancer in women worldwide. In Colombia, CC is the second most frequent cancer among the entire women population and the first among women aged between 15 and 44 years, with an estimated incidence of 24.9 cases/100,000 inhabitants. The main risk factor is infection with one or more high-risk human papillomavirus (HPV) types. The aim of this study was to estimate the genotype-specific prevalence of human papillomavirus (HPV) DNA in patients with cervical pathology using the multiplex PCR and Luminex xMAP technology. In addition, we compared genotyping with Luminex xMAP and with Reverse Line Blot (RLB). A cohort of 160 patients participated in the study, of which 25.6% had no cervical lesions, 35% presented cervical intraepithelial neoplasia of grade I (CIN I), 10% CIN II, 20.6% CIN III and 8.8% CC. The most frequent viral types in all lesion grades were HPV16 and HPV18. Infections by a unique virus were less frequent (19.4%) than multiple infections (80.6%). Single infections were found in 22% of women with no cervical lesions, and in 14.3% of CIN I, 18.7% CIN II, 21.2% CIN III and 28.6% of CC. Multiple infections were observed in 78.0% of cervical samples with negative histopathologic diagnosis, and in 85.7% of CIN I, 81.2% CIN II, 78.8% CIN III and 71.4% CC. All samples analyzed with Luminex xMAP were HPV-positive, while we could detect HPV in only 48.8% of cases with RLB. Of the samples positive by both methods, there was a 67.2% correlation in the viral type(s) detected. In conclusion, Luminex suspension array showed a remarkably higher sensitivity compared with RLB. Multiple infections were unexpectedly common, being HPV types 16 and 18 the most prevalent in all histopathologic grades. PMID:21769306

HPV vaccination and sexual behavior in a community college sample.

PubMed

Marchand, Erica; Glenn, Beth A; Bastani, Roshan

2013-12-01

Many US parents are concerned that vaccinating daughters against human papillomavirus (HPV) will communicate implicit approval for sexual activity and be associated with early or risky sexual behavior (Scarinci et al. in J Womens Health 16(8):1224-1233, 2007; Schuler et al. in Sex Transm Infect 87:349-353, 2011). The aims of this study were to understand (a) whether the HPV vaccine was associated with risky sexual behavior among a diverse sample of female adolescents and young adults, and (b) to better understand the chronology of HPV vaccination and sexual behavior. An anonymous web-based survey was used to collect data from 114 female community college students. T test and Chi square analyses were used to compare vaccinated and unvaccinated groups on age at first intercourse and proportion who had ever had sexual intercourse. Linear multiple regression was used to predict frequency of condom use and number of sexual partners in the past year, using vaccination status and demographic factors as predictors. About 38% reported receiving at least one dose of the HPV vaccine. Many of those vaccinated (45%) received the vaccine after having initiated sexual activity. The proportion of women who were sexually experienced did not differ by HPV vaccine status, nor did age at first intercourse, number of partners in the past year, or frequency of condom use. Current findings suggest that HPV vaccination is not associated with riskier sexual activity for the young women in this sample. Adolescents and their parents may benefit from education about the need to receive the HPV vaccine before onset of sexual activity.

Determinants of HPV vaccination intentions among Dutch girls and their mothers: a cross-sectional study

PubMed Central

2013-01-01

Background The Dutch government recently added universal Human Papilloma Virus (HPV) vaccination for 12-year-old girls to the existing national immunization program. The participation rate for the initial catch-up campaign for girls aged 13 to 16 years in 2009 was lower (47%) than expected (70%). To inform future HPV information campaigns, this paper examines the social and psychological determinants of the HPV vaccination intentions of girls aged 13 to 16 years and their mothers who were targeted by the Dutch catch-up campaign of 2009. Methods A random sample of girls and their mothers was chosen from the Dutch vaccination register and received a letter inviting them to participate (n = 5,998 mothers and daughters). In addition, a random sample was recruited via an online panel by a marketing research company (n = 650 mothers; n = 350 daughters). Both groups were asked to complete a web-based questionnaire with questions on social demographic characteristics, social-psychological factors and HPV vaccination intention. Backward linear regression analyses were conducted to examine which social-psychological factors were most dominantly associated with vaccination intention. Results Data from 952 mothers (14%) and 642 daughters (10%) were available for the intended analyses. The contribution of social demographic variables to the explained variance of HPV vaccination intention was small but significant for mothers (ΔR2 = .01; p = .007), but not significant for daughters (ΔR2 = .02; p = .17) after controlling for HPV vaccination uptake and the sample. In addition, social-psychological determinants largely contributed to the explained variance of HPV vaccination intention of mothers (ΔR2 = .35; p < .001) and daughters (ΔR2 = .34; p < .001). Attitudes, beliefs, subjective norms and habit strength were significantly associated with participants’ HPV vaccination intentions. Conclusions Because of the large contribution of social-psychological variables to the explained variance of HPV vaccination intentions among the mothers and daughters, future communication strategies targeting HPV vaccination uptake should address attitudes, beliefs, subjective norms and habit strength. There is a need for longitudinal research to confirm the causality of the association between these determinants and HPV vaccination behavior indicated by this study. PMID:23388344

Human papillomavirus and Chlamydia trachomatis infection in gyneco-obstetric outpatients from a mexican hospital.

PubMed

Conde-Ferráez, Laura; Martíez, Jorge Ramiro Carrillo; Ayora-Talavera, Guadalupe; Losa, María Del Refugio González

2017-01-01

Human papillomavirus (HPV) and Chlamydia trachomatis are the most frequent sexually transmitted infections, usually asymptomatic. Persistent infection with high-risk HPV types and other cofactors such as the concomitant infection with C. trachomatis can represent a higher risk to develop cervical lesions; therefore, screening with sensitive methods could aid to identify women at risk. The aim is to determine the prevalence and concurrence of both infections, detected with in-house molecular methods, and to identify the risk factors associated to the infections in Mexican women. This was a cross-sectional study including gynaecological-obstetrical medical outpatients from a Social Security Hospital in Southeast Mexico. After informed consent, cervicovaginal samples were collected and tested for HPV and C. trachomatis using polymerase chain reaction (PCR). HPV positives were further tested for high-risk HPV16, 18, 58 and low-risk 11 using real-time PCR. All methods employed were in-house. Data analyses included odds ratios (OR), Chi-square and linear regressions. Women included were 233, aging 15-49 (mean 30 years), 52.8% were pregnant. For HPV and C. trachomatis testing, 230 samples were adequate, resulting in 48 (20.9%) and 15 (6.5%) positives, respectively; 4 (1.7%) were positive to both. The most frequent genotype identified was HPV58 (25% of typified samples). C. trachomatis positives were 73% asymptomatic, none had pelvic inflammatory disease or infertility histories. The only variable associated to HPV infection was the history of previous sexually transmitted disease (OR = 3.69,P= 0.0019). More than 25% of the population was infected with either agent. We successfully used in-house molecular methodologies for diagnosis and typing, showing HPV and C. trachomatis prevalence consistent to previous reports. Concomitant infections were found, HPV high-risk types were involved in half of these cases, representing a higher risk.

Knowledge and beliefs regarding cervical cancer screening and HPV vaccination among urban and rural women in León, Nicaragua

PubMed Central

Lombardo, Alexandra R.; Tangoren, Caroline G.; Meyers, Sara J.; Muppala, Vishnu R.; Niccolai, Linda M.

2017-01-01

Background In Nicaragua, cervical cancer is the leading cause of cancer-related death for women ages 15–44, yet access to the HPV vaccine is limited to those with financial resources to pay for it. Cervical cytology is provided free of charge in public clinics; however, only 10% of women receive Pap smears at the nationally recommended frequency. Previous studies have not investigated how beliefs regarding cervical cancer screening may differ for urban and rural populations in Nicaragua. Furthermore, no investigation has assessed Nicaraguan women’s beliefs about a potential HPV immunization campaign. Given beliefs’ influence on health behavior, we investigated the structural, sociocultural, and knowledge-based factors influencing women’s beliefs regarding cervical cancer screening among urban and rural women in León, Nicaragua, and assessed acceptance of a potential HPV immunization program. Methods Our sequential explanatory mixed-methods study consisted of two phases: (1) a close-ended questionnaire, followed by (2) a qualitative, in-depth interview. Our quantitative sample contained 117 urban and 112 rural participants aged 18–49. We assessed beliefs regarding cervical cancer screening using a 22-item scale, with higher scores indicating screening-promoting beliefs in simple linear and multiple linear regressions. Twenty qualitative interviews, exploring the sociocultural dimensions of knowledge and attitudes indicated by our quantitative findings, were conducted with a sample of 13 urban and 7 rural women aged 19–46. Results The multiple linear regression indicates that greater knowledge of Pap smears, HPV, and cervical cancer is significantly associated with screening-promoting beliefs after adjusting for other relevant factors. There was no significant difference in screening knowledge and beliefs for urban and rural women. Four recurrent themes representing determinants of knowledge, beliefs, and attitudes regarding cervical cancer screening arose from interviews and built on quantitative findings: (1) women’s embarrassment due to the intimate nature of the Pap smear and male gender of exam provider discourages screening; (2) women believe Pap smears and cervical cancer are associated with sexual promiscuity, and this association stigmatizes women with the disease; (3) knowledge of cervical cancer prevention is limited to those who regularly attend health centers; and (4) women find screening inconvenient, believing understaffed clinics increase patient wait time, limit time patients spend with clinicians, and delay Pap results. A fifth theme indicates (5) participants’ acceptance of a potential HPV immunization program. Discussion Future interventions should focus on increasing access to information about cervical cancer prevention for women who do not regularly attend health centers. Furthermore, our results suggest that if funding were allocated to make the HPV vaccine accessible in Nicaragua, it would be well received. PMID:29085745

Knowledge and beliefs regarding cervical cancer screening and HPV vaccination among urban and rural women in León, Nicaragua.

PubMed

Rees, Hannah D; Lombardo, Alexandra R; Tangoren, Caroline G; Meyers, Sara J; Muppala, Vishnu R; Niccolai, Linda M

2017-01-01

In Nicaragua, cervical cancer is the leading cause of cancer-related death for women ages 15-44, yet access to the HPV vaccine is limited to those with financial resources to pay for it. Cervical cytology is provided free of charge in public clinics; however, only 10% of women receive Pap smears at the nationally recommended frequency. Previous studies have not investigated how beliefs regarding cervical cancer screening may differ for urban and rural populations in Nicaragua. Furthermore, no investigation has assessed Nicaraguan women's beliefs about a potential HPV immunization campaign. Given beliefs' influence on health behavior, we investigated the structural, sociocultural, and knowledge-based factors influencing women's beliefs regarding cervical cancer screening among urban and rural women in León, Nicaragua, and assessed acceptance of a potential HPV immunization program. Our sequential explanatory mixed-methods study consisted of two phases: (1) a close-ended questionnaire, followed by (2) a qualitative, in-depth interview. Our quantitative sample contained 117 urban and 112 rural participants aged 18-49. We assessed beliefs regarding cervical cancer screening using a 22-item scale, with higher scores indicating screening-promoting beliefs in simple linear and multiple linear regressions. Twenty qualitative interviews, exploring the sociocultural dimensions of knowledge and attitudes indicated by our quantitative findings, were conducted with a sample of 13 urban and 7 rural women aged 19-46. The multiple linear regression indicates that greater knowledge of Pap smears, HPV, and cervical cancer is significantly associated with screening-promoting beliefs after adjusting for other relevant factors. There was no significant difference in screening knowledge and beliefs for urban and rural women. Four recurrent themes representing determinants of knowledge, beliefs, and attitudes regarding cervical cancer screening arose from interviews and built on quantitative findings: (1) women's embarrassment due to the intimate nature of the Pap smear and male gender of exam provider discourages screening; (2) women believe Pap smears and cervical cancer are associated with sexual promiscuity, and this association stigmatizes women with the disease; (3) knowledge of cervical cancer prevention is limited to those who regularly attend health centers; and (4) women find screening inconvenient, believing understaffed clinics increase patient wait time, limit time patients spend with clinicians, and delay Pap results. A fifth theme indicates (5) participants' acceptance of a potential HPV immunization program. Future interventions should focus on increasing access to information about cervical cancer prevention for women who do not regularly attend health centers. Furthermore, our results suggest that if funding were allocated to make the HPV vaccine accessible in Nicaragua, it would be well received.

InterSCOPE Study: Associations Between Esophageal Squamous Cell Carcinoma and Human Papillomavirus Serological Markers

PubMed Central

Egger, Sam; Urban, Margaret I.; Taylor, Philip R.; Abnet, Christian C.; Boffetta, Paolo; O’Connell, Dianne L.; Whiteman, David C.; Brennan, Paul; Malekzadeh, Reza; Pawlita, Michael; Dawsey, Sanford M.; Waterboer, Tim; Webb, Penelope M.; Green, Adèle C.; Hayward, Nicholas K.; Zaridze, David; Holcatova, Ivana; Mates, Dana; Szeszenia-Dabrowska, Neonila; Ferro, Gilles; Janout, Vladimir; Curado, Maria Paula; Menezes, Ana Maria; Koifman, Sergio; Islami, Farhad; Nasrollahzadeh, Dariush; Hu, Nan; Goldstein, Alisa M.; Gao, Ying; Ding, Ti; Kamangar, Farin

2012-01-01

Background The role of human papillomavirus (HPV) in the causation of esophageal squamous cell carcinoma is unclear. We examined the associations between esophageal squamous cell carcinoma and 28 centrally measured HPV serological markers in serum from six existing case–control studies conducted in regions with differing background risks of esophageal cancer. Methods We used centralized multiplex serology to test serum samples from 1561 case subjects and 2502 control subjects from six case–control studies for antibodies to the major HPV capsid protein (L1) and/or the early proteins E6 and/or E7 of eight high-risk, two low-risk, and four cutaneous HPV types. Study-specific odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using conditional logistic regression with adjustment for smoking, alcohol consumption, and other potential confounders. Pooled odds ratios and 95% confidence intervals were calculated using either a linear mixed-effects approach or a joint fixed-effects approach. All statistical tests were two-sided. Results We found statistically significant associations between esophageal squamous cell carcinoma and antibodies to E6 for HPV16 (OR = 1.89, 95% CI = 1.09 to 3.29, P = .023) and HPV6 (OR = 2.53, 95% CI = 1.51 to 4.25, P < .001) but not for other tested HPV types. There were no statistically significant associations between esophageal squamous cell carcinoma and antibodies to E7 for any of the tested HPV types. Simultaneous seropositivity for HPV16 E6 and E7 was rare (four case subjects, two control subjects; OR = 5.57, 95% CI = 0.90 to 34.35; P = .064). We also found statistically significant associations between esophageal squamous cell carcinoma and capsid antibodies for the high-risk mucosal type HPV33 L1 (OR = 1.30, 95% CI = 1.00 to 1.69; P = .047) and the low-risk mucosal types HPV6 (OR = 1.22, 95% CI = 1.05 to 1.42; P = .010) and HPV11 (OR = 1.30, 95% CI = 1.09 to 1.56, P = .0036). Conclusions We found limited serological evidence of an association between esophageal squamous cell carcinoma and HPV in the populations studied. Although HPV does not appear to be an important risk factor for esophageal squamous cell carcinoma, we cannot exclude the possibility that certain HPV types may be involved in a small subset of cancers. PMID:22228147

Epitomics: IgG-epitome decoding of E6, E7 and L1 proteins from oncogenic human papillomavirus type 58

PubMed Central

Xu, Wan-Xiang; Wang, Jian; Tang, Hai-Ping; He, Ya-Ping; Zhu, Qian-Xi; Gupta, Satish K.; Gu, Shao-Hua; Huang, Qiang; Ji, Chao-Neng; Liu, Ling-Feng; Li, Gui-Ling; Xu, Cong-Jian; Xie, Yi

2016-01-01

To enable rational multi-epitope vaccine and diagnostic antigen design, it is imperative to delineate complete IgG-epitome of the protein. Here, we describe results of IgG-epitome decoding of three proteins from high-risk (HR-) oncogenic human papillomavirus type 58 (HPV58). To reveal their entire epitomes, employing peptide biosynthetic approach, 30 precise linear B-cell epitopes (BCEs) were mapped on E6, E7 and L1 proteins using rabbits antisera to the respective recombinant proteins. Using sequence alignment based on BCE minimal motif, the specificity and conservativeness of each mapped BCE were delineated mainly among known HR-HPVs, including finding 3 broadly antibody cross-reactive BCEs of L1 that each covers almost all HR-HPVs. Western blots revealed that 13 of the 18 BCEs within L1-epitome were recognized by murine antisera to HPV58 virus-like particles, suggesting that these are antibody accessible BCEs. Also, a highly conserved epitope (YGD/XTL) of E6 was found to exist only in known common HR-HPVs, which could be used as the first peptide reference marker for judging HR-HPVs. Altogether, this study provides systemic and exhaustive information on linear BCEs of HR-HPV58 that will facilitate development of novel multi-epitope diagnostic reagents/chips for testing viral antibodies and ‘universal’ preventive HPV peptide vaccine based on L1 conserved BCEs. PMID:27708433

Psychological Impact of Primary Screening (PIPS) for HPV: a protocol for a cross-sectional evaluation within the NHS cervical screening programme.

PubMed

McBride, Emily; Marlow, Laura; Forster, Alice S; Moss, Sue; Myles, Jonathan; Kitchener, Henry; Patnick, Julietta; Waller, Jo

2016-12-23

The NHS Cervical Screening Programme is now using human papillomavirus (HPV) testing as the primary test in six sentinel sites in England, with the intention of rolling this out across the whole of England. Previous research evaluating HPV testing in the cervical screening context suggests that an HPV-positive result may increase anxiety beyond that associated with abnormal cytology, but this has not been explored in the context of primary HPV testing. The main aim of this study is to explore the impact of the HPV primary screening programme on anxiety and distress. A cross-sectional between-groups design (total N ∼ 673) will be employed to assess the psychological impact of different HPV and cytology results at three time points: shortly after receiving the results, and 6 and 12 months later. Women will fall into one of six groups based on their screening results. The primary outcomes will be anxiety and general distress. Secondary outcomes will include understanding of screening results, perceived risk of cervical cancer, psychosexual functioning, intention to attend future screening and knowledge of HPV. General linear modelling will be used to test for differences between groups and changes over the three time points. Health Research Authority approval was received on 26 September 2016. Ethical approval was received from London- Surrey Borders NHS Research Ethics Committee on 30 August 2016. Section 251 approval was received from the Confidentiality Advisory Group on 24 August 2016. Results will be disseminated via peer-reviewed publication and presentation at national and international conferences. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Distress levels in patients with oropharyngeal vs. non-oropharyngeal squamous cell carcinomas of the head and neck over 1 year after diagnosis: a retrospective cohort study.

PubMed

Schorr, Melissa; Carlson, Linda E; Lau, Harold Y; Zhong, Lihong; Bultz, Barry D; Waller, Amy; Groff, Shannon L; Hao, Desiree

2017-10-01

Human papillomavirus (HPV)-related cancers have been associated with different demographic profiles and disease characteristics than HPV-unrelated cancers in head and neck patients, but distress and other symptoms have not been compared. The aim of this study was to assess whether distress levels, fatigue, pain, anxiety, depression, and common psychological and practical problems differ between head and neck cancer patients with HPV-related vs. HPV-unrelated carcinomas (using oropharyngeal carcinoma (OPC) and non-OPC cancers as surrogates for HPV status). Distress, depression, anxiety, fatigue, pain, and common problems were examined in 56 OPC and 90 non-OPC patients at 4 timepoints during the first year following diagnosis. Two-level hierarchical linear modeling was used to examine effects. The HPV-related OPC group was more likely to be younger (p = 0.05), Caucasian (p = 0.001), non-smokers (p = 0.01), earn more (p = 0.04), and present with more advanced stage (p < 0.0001). At baseline, OPC patients reported only higher pain scores (p = 0.01) than non-OPC patients. Total problems decreased more in the OPC group (p = 0.08) than the non-OPC group from baseline to 12-month follow-up. In both groups, scores on distress, depression, psychosocial problems, and practical problems decreased similarly over time. Despite a difference in the clinico-demographic characteristics of HPV-related vs. HPV-unrelated patients, only baseline pain levels and total problems over time differed between the two groups.

Human Papillomavirus Infection and its Vaccines: Knowledge and Attitudes of Primary Health Clinic Nurses in Kelantan, Malaysia.

PubMed

Jeyachelvi, K; Juwita, S; Norwati, D

2016-01-01

Cervical cancer though preventable is still the leading cause of cancer death among women secondary to breast cancer. Persistent infection with HPV has been causally linked to the disease. A school based HPV vaccination program was introduced in late 2010 in Malaysia and nurse support is essential for its success. To determine nurses knowledge and attitudes about HPV infection and its vaccines, and factors associated with their knowledge. This cross-sectional study was conducted among nurses working at primary health clinics in Kelantan from mid-June till the end of July 2014. Its involved 330 nurses selected through multistage random sampling. A validated self-administered questionnaire consisting of 11 items for the knowledge domain and eight items for the attitude domain was used. The response rate of the study was 93.7%. The mean knowledge and mean attitude (SD) scores were 5.37 (1.76) and 29.8 (3.51) respectively. Only 24% knew that HPV is the most common sexually transmitted infection and 67% correctly answered that Gardasil vaccine can protect against four types of HPV. Nearly 60% of participants wrongly answered that HPV vaccines cannot be offered to sexually active women. Likewise, 70.9% participants were not aware that HPV vaccine may be appropriate for females aged 9 through 26 years. Though 90% of participants believed that the vaccine is safe, nearly half of them were unsure about efficacy. From multiple linear regression analysis, among the factors tested only participant's level of education showed a statistically significant association with the HPV knowledge score (<0.001). This study indicates nurses have favorable attitudes towards HPV vaccination; however they have significant knowledge deficit and major misunderstanding in critical knowledge items. Among the factors tested, nursing qualification is the only factor that is significantly associated with the nurses knowledge score.

The role of media and the Internet on vaccine adverse event reporting: a case study of human papillomavirus vaccination.

PubMed

Eberth, Jan M; Kline, Kimberly N; Moskowitz, David A; Montealegre, Jane R; Scheurer, Michael E

2014-03-01

This study aimed to determine the temporal association of print media coverage and Internet search activity with adverse events reports associated with the human papillomavirus vaccine Gardasil (HPV4) and the meningitis vaccine Menactra (MNQ) among United States adolescents. We used moderated linear regression to test the relationships between print media reports in top circulating newspapers, Internet search activity, and reports to the Vaccine Adverse Event Reporting System (VAERS) for HPV4 and MNQ during the first 2.5 years after Food and Drug Administration approval. Compared with MNQ, HPV4 had more coverage in the print media and Internet search activity, which corresponded with the frequency of VAERS reports. In February 2007, we observed a spike in print media for HPV4. Although media coverage waned, Internet search activity remained stable and predicted the rise in HPV4-associated VAERS reports. We demonstrate that media coverage and Internet search activity, in particular, may promote increased adverse event reporting. Public health officials who have long recognized the importance of proactive engagement with news media must now consider strategies for meaningful participation in Internet discussions. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

DNA methylation regulated microRNAs in HPV-16-induced head and neck squamous cell carcinoma (HNSCC).

PubMed

Sannigrahi, M K; Sharma, Rajni; Singh, Varinder; Panda, Naresh K; Rattan, Vidya; Khullar, Madhu

2018-02-17

Epigenetic modifications have been reported to play an important role in regulating gene expression and these modifications become critical when they have a role in controlling another important layer of epigenetic regulation namely microRNAs. In the present study, we have identified the microRNAs that may be regulated by promoter DNA methylation and histone acetylation in Human papilloma virus-positive head and neck squamous cell carcinoma. HPV-negative cell line (UPCI:SCC-116) and HPV-16 +ve cell line (UPCI:SCC-090) were treated with methylation inhibitor (5-aza-2'-deoxycytidine, AZA) and acetylation inhibitor (Trichostatin-A, TSA), followed by micro-array analysis. The differentially expressed miRNAs were validated in control (n = 10), HPV-16 +ve (n = 30), and HPV -ve (n = 30) HNC, TCGA (n = 529) tissue samples, and two HPV -ve (SCC116 and Hacat) and two HPV +ve (SCC090 and SiHa) cell lines. Methylation-specific PCR (MSP) and chromatin immunoprecipitation assay (CHIP) were performed to validate their regulation. In silico and in vitro analyses of identified miRNAs were done to study putative pathways they target and their possible role in carcinogenesis. Among 10 miRNAs specifically up-regulated in microarray analysis of AZA-treated SCC090 cells, we observed significantly decreased expression of hsa-miR-181c-5p, hsa-miR-132-5p, hsa-miR-658 in HPV +ve HNC cohort, TCGA tissue samples, and cell lines as compared to their HPV -ve counterpart, and their promoter region also possesses CpG islands. MSP and analysis of TCGA data (MethHC) revealed increased frequency of methylation at the promoter of hsa-miR-132-5p that is negatively correlated with its expression. In TSA-treated SCC090 cells, out of 7 miRNAs, two namely Hsa-miR-129-2-3p and Hsa-miR-449a were found to be up-regulated as compared to HPV -ve cells. However, the levels of enrichment by anti-acetyl-H3 and anti-acetyl-H4 were significantly low in cell lines compared to respective controls and both were up-regulated in HPV +ve compared to HPV -ve TCGA tissue samples. In silico analysis revealed hsa-miR-132-5p targeted canonical β-catenin/wnt pathway and modulation of down-stream genes of the pathway was observed on over-expression/inhibition of hsa-miR-132-5p. This study suggests the role of epigenetic modifications in regulating expression of miRNAs in HPV +ve HNSCC.

Treatment of vulvar/vaginal condyloma by HPV: developed instrumentation and clinical report

NASA Astrophysics Data System (ADS)

Inada, N. M.; Kurachi, C.; Ferreira, J.; Ribeiro, E. S.; Guimarães, O. C. C.; Quintana, S. M.; Lombardi, W.; Bagnato, V. S.

2009-06-01

Human papillomavirus (HPVs) are a family of sexually viruses with over 100 different genotypes identified till date. They are associated in 99% of cervical cancers, with HPV16 found in about 50% of cases. They are a cause of the second most common female cancer worldwide. PDT may constitute an alternative treatment for condyloma by HPV. In this work we present the development of a PDT device specifically designed for the treatment of vulvar and vaginal lesions induced by HPV. This equipment has been used in a clinical protocol and it is optically based on 640 nm LED (light emitting diodes) arrays. There are three illumination probes available that were anatomically designed for specific site applications: a 30 mm x 115 mm diffuser cylinder for intravaginal illumination and uniform irradiance of 42 mW/cm2; a 36 mm circular probe with 118 mW/cm2 and a 74 mm circular probe with 57 mW/cm2, both for external illumination. The 10% aminolevulinic acid cream is topically placed over the lesions and 4-6 hours after the application the illumination is performed. The illumination time is set depending on the chosen probe and treatment area to achieve a fluence of 200 J/cm2. In this presentation, the preliminary results of this clinical trial will be presented.

Contemporary theories of cervical carcinogenesis: the virus, the host, and the stem cell.

PubMed

Crum, C P

2000-03-01

Cervical cancer is a complex disease that, by its association with human papillomavirus (HPV), has elicited research in a broad range of areas pertaining to its basic diagnostic and clinical aspects. The complexity of this association lies not only in the fundamental relationship between virus and cancer but also in its translation to pathologic diagnosis and clinical management. Offshoots from the relationship of virus to pathology include studies targeting the link between papillomavirus infection and cervical epithelial abnormalities, the molecular epidemiology of papillomavirus infection, and the potential use of HPV testing as either a screening technique or a tool for managing women who have Pap smear abnormalities. A second variable that is critical to the pathogenesis of cervical neoplasia is the cervical transformation zone. The wide range of invasive and noninvasive lesion phenotypes associated with HPV infection in this region indicate that not only the virus but also specific host target epithelial cells in the transformation zone play an important part in the development of cervical neoplasia. Further understanding of this relationship between the virus and the host epithelium will hinge on determining the subtypes of epithelial cells in the transformation zone and their phenotypic response to infection. New technologies, such as expression arrays, promise to clarify, if not resolve, the complexity of molecular interactions leading to the multiplicity of tumor phenotypes associated with HPV infection of the uterine cervix.

Human Papillomavirus Vaccine-Related Risk Perceptions and Subsequent Sexual Behaviors and Sexually Transmitted Infections among Vaccinated Adolescent Women

PubMed Central

Mullins, Tanya L. Kowalczyk; Zimet, Gregory D.; Rosenthal, Susan L.; Morrow, Charlene; Ding, Lili; Huang, Bin; Kahn, Jessica A.

2016-01-01

Objective To examine the association between risk perceptions after human papillomavirus (HPV) vaccination and sexual behaviors and sexually transmitted infection (STI) diagnosis over 30 months following vaccination. Methods Participants included 112 sexually experienced girls aged 13–21 years who were enrolled at the time of first HPV vaccination and completed ≥2 of 4 follow-up visits at 2, 6, 18, 30 months and including 30 months. At each visit, participants completed surveys assessing risk perceptions (perceived need for safer sexual behaviors, perceived risk of STIs other than HPV) and sexual behaviors. STI testing was done at 6, 18, and 30 months. Outcomes were condom use at last intercourse with main male partner, number of sexual partners since last study visit, and STI diagnosis. Associations between risk perceptions and sexual behaviors/STIs were examined using generalized linear mixed models. Results Mean age was 17.9 years; 88% were Black; 49% had a history of STI at baseline. Scale scores for perceived need for safer sexual behaviors did not change significantly over time. Scale scores for perceived risk of STIs other than HPV significantly changed (p=0.027), indicating that girls perceived themselves to be more at risk of STIs other than HPV over 30 months following vaccination. Multivariable models demonstrated that greater perceived need for safer sexual behaviors following vaccination was associated with condom use (p=0.002) but not with number of partners or STI diagnosis. Perceived risk of STIs other than HPV was not associated with the three outcomes. Conclusions The finding that perceived risk for STIs other than HPV was not associated with subsequent sexual behaviors or STI diagnosis is reassuring. The association between perceived need for safer sexual behaviors and subsequent condom use suggests that the HPV vaccination visit is an important opportunity to reiterate the importance of safer sexual behaviors to sexually experienced girls. PMID:27291086

VIRAL LOAD AND SHORT-TERM NATURAL HISTORY OF TYPE-SPECIFIC ONCOGENIC HUMAN PAPILLOMAVIRUS INFECTIONS IN A HIGH-RISK COHORT OF MID-ADULT WOMEN

PubMed Central

Winer, Rachel L.; Xi, Long Fu; Shen, Zhenping; Stern, Joshua E.; Newman, Laura; Feng, Qinghua; Hughes, James P.; Koutsky, Laura A.

2013-01-01

Oncogenic human papillomavirus (HPV) viral load may inform the origin of newly detected infections and characterize oncogenic HPV natural history in mid-adult women. From 2007–2011, we enrolled 521 25–65 year old female online daters and followed them triannually with mailed health and sexual behavior questionnaires and kits for self-sampling for PCR-based HPV DNA testing. Samples from oncogenic HPV positive women were selected for type-specific DNA load testing by real-time PCR with adjustment for cellularity. Linear or logistic regression models were used to evaluate relationships between viral levels, health and sexual behavior, and longitudinal oncogenic HPV detection. Type-specific viral levels were borderline significantly higher in oncogenic HPV infections that were prevalent versus newly detected (p=0.092), but levels in newly detected infections were higher than in infections re-detected after intercurrent negativity (p<.001). Recent sex partners were not significantly associated with viral levels. Compared to prevalent infections detected intermittently, the likelihood of persistent (OR=4.31,95%CI:2.20–8.45) or single-time (OR=1.32,95%CI:1.03–1.71) detection increased per 1-unit increase in baseline log10 viral load. Viral load differences between re-detected and newly detected infections suggest a portion of new detections were due to new acquisition, although report of recent new sex partners (a potential marker of new infection) was not predictive of viral load; oncogenic HPV infections in mid-adult women with new partners likely represent a mix of new acquisition and reactivation or intermittent detection of previous infection. Intermittent detection was characterized by low viral levels, suggesting that intermittent detection of persisting oncogenic HPV infection may be of limited clinical significance PMID:24136492

Multispectral linear array visible and shortwave infrared sensors

NASA Astrophysics Data System (ADS)

Tower, J. R.; Warren, F. B.; Pellon, L. E.; Strong, R.; Elabd, H.; Cope, A. D.; Hoffmann, D. M.; Kramer, W. M.; Longsderff, R. W.

1984-08-01

All-solid state pushbroom sensors for multispectral linear array (MLA) instruments to replace mechanical scanners used on LANDSAT satellites are introduced. A buttable, four-spectral-band, linear-format charge coupled device (CCD) and a buttable, two-spectral-band, linear-format, shortwave infrared CCD are described. These silicon integrated circuits may be butted end to end to provide multispectral focal planes with thousands of contiguous, in-line photosites. The visible CCD integrated circuit is organized as four linear arrays of 1024 pixels each. Each array views the scene in a different spectral window, resulting in a four-band sensor. The shortwave infrared (SWIR) sensor is organized as 2 linear arrays of 512 detectors each. Each linear array is optimized for performance at a different wavelength in the SWIR band.

Resolution of Port/Starboard Ambiguity Using a Linear Array of Triplets and a Twin-Line Planar Array

DTIC Science & Technology

2016-06-01

STARBOARD AMBIGUITY USING A LINEAR ARRAY OF TRIPLETS AND A TWIN- LINE PLANAR ARRAY by Stilson Veras Cardoso June 2016 Thesis Advisor...OF TRIPLETS AND A TWIN-LINE PLANAR ARRAY 5. FUNDING NUMBERS 6. AUTHOR(S) Stilson Veras Cardoso 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES...A LINEAR ARRAY OF TRIPLETS AND A TWIN-LINE PLANAR ARRAY Stilson Veras Cardoso Civilian, Brazilian Navy B.S., University of Brasília, 1993

T Cells that Recognize HPV Protein Can Target Virus-Infected Cells | Center for Cancer Research

Cancer.gov

Adoptive T-cell transfer (ACT) is a promising form of cancer immunotherapy. Treating patients with T cells isolated from a tumor and subsequently expanded in the lab can cause the complete regression of some melanomas and cervical cancers, but the treatment is currently restricted to a few cancer types. An approach that may be applied to a wider array of cancers involves

E6 and E7 Antibody Levels Are Potential Biomarkers of Recurrence in Patients with Advanced-Stage Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma.

PubMed

Spector, Matthew E; Sacco, Assuntina G; Bellile, Emily; Taylor, Jeremy M G; Jones, Tamara; Sun, Kan; Brown, William C; Birkeland, Andrew C; Bradford, Carol R; Wolf, Gregory T; Prince, Mark E; Moyer, Jeffrey S; Malloy, Kelly; Swiecicki, Paul; Eisbruch, Avraham; McHugh, Jonathan B; Chepeha, Douglas B; Rozek, Laura; Worden, Francis P

2017-06-01

Purpose: There is a paucity of biomarkers to predict failure in human papillomavirus-positive (HPV + ) oropharyngeal squamous cell carcinoma (OPSCC) following curative therapy. E6/E7 viral oncoproteins are constitutively expressed in HPV + tumors and highly immunogenic, resulting in readily detected serum antibodies. The purpose of this study is to determine whether serum E6 and E7 antibody levels can potentially serve as a biomarker of recurrence in patients with HPV+OPSCC. Experimental Design: We evaluated E6/E7 antibody levels in patients with previously untreated, advanced stage (III, IVa-b), HPV+OPSCC receiving definitive chemoradiation under a uniform protocol from 2003 to 2010. Baseline and longitudinal serum samples were obtained from our archived repository. E6/E7 serum levels were measured using a glutathione- S -transferase capture ELISA and quantified by approximating the area under the dilution curve, and were analyzed using ANOVA and linear mixed model for longitudinal analysis. Results: We compared 22 HPV+OPSCC patients who developed recurrence with 30 patients who remained disease-free. There were no differences in T classification, N classification, disease subsite, or smoking status between the groups. In a longitudinal analysis, recurrent patients had significantly higher E6 and E7 serum antibody levels than the nonrecurrent patients over the follow-up period ( P = 0.02 and P = 0.002, respectively). Patients who recurred had a lower clearance of E7 antibody than patients who remained disease-free ( P = 0.0016). Conclusions: Patients with HPV+OPSCC whose disease recurs have a lower clearance of E6 and E7 antibodies than patients who do not have recurrence. The ratio of E7 antibody at disease recurrence compared with baseline is potentially a clinically significant measurement of disease status in HPV+OPSCC. Clin Cancer Res; 23(11); 2723-9. ©2016 AACR . ©2016 American Association for Cancer Research.

A longitudinal study on determinants of HPV vaccination uptake in parents/guardians from different ethnic backgrounds in Amsterdam, the Netherlands.

PubMed

Alberts, Catharina J; van der Loeff, Maarten F Schim; Hazeveld, Yvonne; de Melker, Hester E; van der Wal, Marcel F; Nielen, Astrid; El Fakiri, Fatima; Prins, Maria; Paulussen, Theo G W M

2017-02-21

Human papillomavirus (HPV) vaccination coverage in the Netherlands is low (~60%) compared to other childhood vaccinations (>90%), and even lower among ethnic minorities. The aim of this study was to explore the possible impact of ethnicity on the determinants of both HPV vaccination intention and HPV vaccination uptake among parents/guardians having a daughter that is invited for the HPV vaccination. In February 2014, parents/guardians living in Amsterdam were invited to complete a questionnaire about social-psychological determinants of their decision making process regarding the HPV vaccination of their daughter and socio-demographic characteristics. This questionnaire was sent approximately one month before the daughter was scheduled to receive her first HPV vaccine dose. Their daughters' HPV vaccination status was retrieved from the national vaccination database. We distinguished four ethnic groups: Dutch (NL), Surinamese, Netherlands Antillean, and Aruban (SNA), Middle-Eastern and North-African (MENA), and Other. To assess the impact of determinants on both intention and uptake, linear and logistic regression analyses were used respectively. Missing data were imputed using multiple imputation by chained equation. In total 1,309 parents/guardians participated (33% participation rate). In all groups we found the mothers' intention to be the strongest predictor of their daughters' HPV vaccination uptake. Explained variance of uptake was highest in the NL-group (pseudo-R 2 :0.56) and lower in the other ethnic groups (pseudo-R 2 varied between 0.23 and 0.29). The lower explained variance can be attributed to the relative large proportion of participants with a positive intention that finally did not go for vaccination in the SNA-group (11%) and MENA-group (30%). Explained variance (R 2 ) of intention varied between 0.66 and 0.77 across ethnic groups, and was best explained by the proximal social-psychological determinants. The strength of association of these determinants with both intention and uptake were largely similar across ethnic groups. We conclude that the same determinants should be targeted in the different ethnic groups, although the mode of delivery of the intervention needs to be tailored to the different cultural backgrounds. Further research is needed to explain the observed discrepancy between intention and uptake, especially among parents/guardians in the non-Dutch groups.

Incoming human papillomavirus 16 genome is lost in PML protein-deficient HaCaT keratinocytes.

PubMed

Bienkowska-Haba, Malgorzata; Luszczek, Wioleta; Keiffer, Timothy R; Guion, Lucile G M; DiGiuseppe, Stephen; Scott, Rona S; Sapp, Martin

2017-05-01

Human papillomaviruses (HPVs) target promyelocytic leukemia (PML) nuclear bodies (NBs) during infectious entry and PML protein is important for efficient transcription of incoming viral genome. However, the transcriptional down regulation was shown to be promoter-independent in that heterologous promoters delivered by papillomavirus particles were also affected. To further investigate the role of PML protein in HPV entry, we used small hairpin RNA to knockdown PML protein in HaCaT keratinocytes. Confirming previous findings, PML knockdown in HaCaT cells reduced HPV16 transcript levels significantly following infectious entry without impairing binding and trafficking. However, when we quantified steady-state levels of pseudogenomes in interphase cells, we found strongly reduced genome levels compared with parental HaCaT cells. Because nuclear delivery was comparable in both cell lines, we conclude that viral pseudogenome must be removed after successful nuclear delivery. Transcriptome analysis by gene array revealed that PML knockdown in clonal HaCaT cells was associated with a constitutive interferon response. Abrogation of JAK1/2 signaling prevented genome loss, however, did not restore viral transcription. In contrast, knockdown of PML protein in HeLa cells did not affect HPV genome delivery and transcription. HeLa cells are transformed by HPV18 oncogenes E6 and E7, which have been shown to interfere with the JAK/Stat signaling pathway. Our data imply that PML NBs protect incoming HPV genomes. Furthermore, they provide evidence that PML NBs are key regulators of the innate immune response in keratinocytes. Promyelocytic leukemia nuclear bodies (PML NBs) are important for antiviral defense. Many DNA viruses target these subnuclear structures and reorganize them. Reorganization of PML NBs by viral proteins is important for establishment of infection. In contrast, HPVs require the presence of PML protein for efficient transcription of incoming viral genome. Our finding that PML protein prevents the loss of HPV genome following infection implies that the host cell may be able to recognize chromatinized HPV genome or the associated capsid proteins. A constitutively active interferon response in absence of PML protein suggests that PML NBs are key regulators of the innate immune response in keratinocytes. © 2016 John Wiley & Sons Ltd.

The presence of human papillomavirus in semen does not affect the integrity of sperm DNA.

PubMed

Cortés-Gutiérrez, E I; Dávila-Rodríguez, M I; Fernández, J L; de la O-Pérez, L O; Garza-Flores, M E; Eguren-Garza, R; Gosálvez, J

2017-12-01

It remains unknown whether human papillomaviruses (HPVs) in semen affect sperm DNA integrity. We investigated whether the presence of these viruses in semen was associated with an elevated sperm DNA fragmentation index. Semen samples of 22 normozoospermic patients undergoing infertility treatment, nine fertile donors and seven fertile men with a risk of HPV infection (genital warts or condylomas) were included in the study. The samples were examined by an INNO-LiPA test PCR-based reverse hybridisation array that identifies 28 types of HPVs as simple or multiple infections. Sperm DNA integrity was determined by sperm chromatin dispersion assay (SCD). Our preliminary findings demonstrate an increase in HPV infection in infertile men with respect to fertile men. However, the sperm DNA fragmentation index was not increased in semen containing these viruses. © 2017 Blackwell Verlag GmbH.

Breadboard linear array scan imager using LSI solid-state technology

NASA Technical Reports Server (NTRS)

Tracy, R. A.; Brennan, J. A.; Frankel, D. G.; Noll, R. E.

1976-01-01

The performance of large scale integration photodiode arrays in a linear array scan (pushbroom) breadboard was evaluated for application to multispectral remote sensing of the earth's resources. The technical approach, implementation, and test results of the program are described. Several self scanned linear array visible photodetector focal plane arrays were fabricated and evaluated in an optical bench configuration. A 1728-detector array operating in four bands (0.5 - 1.1 micrometer) was evaluated for noise, spectral response, dynamic range, crosstalk, MTF, noise equivalent irradiance, linearity, and image quality. Other results include image artifact data, temporal characteristics, radiometric accuracy, calibration experience, chip alignment, and array fabrication experience. Special studies and experimentation were included in long array fabrication and real-time image processing for low-cost ground stations, including the use of computer image processing. High quality images were produced and all objectives of the program were attained.

System and method for 100% moisture and basis weight measurement of moving paper

DOEpatents

Hernandez, Jose E.; Koo, Jackson C.

2002-01-01

A system for characterizing a set of properties for a moving substance are disclosed. The system includes: a first near-infrared linear array; a second near-infrared linear array; a first filter transparent to a first absorption wavelength emitted by the moving substance and juxtaposed between the substance and the first array; a second filter blocking the first absorption wavelength emitted by the moving substance and juxtaposed between the substance and the second array; and a computational device for characterizing data from the arrays into information on a property of the substance. The method includes the steps of: filtering out a first absorption wavelength emitted by a substance; monitoring the first absorption wavelength with a first near-infrared linear array; blocking the first wavelength from reaching a second near-infrared linear array; and characterizing data from the arrays into information on a property of the substance.

Multienzyme-nanoparticles amplification for sensitive virus genotyping in microfluidic microbeads array using Au nanoparticle probes and quantum dots as labels.

PubMed

Zhang, He; Liu, Lian; Li, Cheuk-Wing; Fu, Huayang; Chen, Yao; Yang, Mengsu

2011-11-15

A novel microfluidic device with microbeads array was developed and sensitive genotyping of human papillomavirus was demonstrated using a multiple-enzyme labeled oligonucleotide-Au nanoparticle bioconjugate as the detection tool. This method utilizes microbeads as sensing platform that was functionalized with the capture probes and modified electron rich proteins, and uses the horseradish peroxidase (HRP)-functionalized gold nanoparticles as label with a secondary DNA probe. The functionalized microbeads were independently introduced into the arrayed chambers using the loading chip slab. A single channel was used to generate weir structures to confine the microbeads and make the beads array accessible by microfluidics. Through "sandwich" hybridization, the enzyme-functionalized Au nanoparticles labels were brought close to the surface of microbeads. The oxidation of biotin-tyramine by hydrogen peroxide resulted in the deposition of multiple biotin moieties onto the surface of beads. This deposition is markedly increased in the presence of immobilized electron rich proteins. Streptavidin-labeled quantum dots were then allowed to bind to the deposited biotin moieties and displayed the signal. Enhanced detection sensitivity was achieved where the large surface area of Au nanoparticle carriers increased the amount HRP bound per sandwiched hybridization. The on-chip genotyping method could discriminate as low as 1fmol/L (10zmol/chip, SNR>3) synthesized HPV oligonucleotides DNA. The chip-based signal enhancement of the amplified assay resulted in 1000 times higher sensitivity than that of off-chip test. In addition, this on-chip format could discriminate and genotype 10copies/μL HPV genomic DNA using the PCR products. These results demonstrated that this on-chip approach can achieve highly sensitive detection and genotyping of target DNA and can be further developed for detection of disease-related biomolecules at the lowest level at their earliest incidence. Copyright © 2011 Elsevier B.V. All rights reserved.

Molecular evidence of viral DNA in non-small cell lung cancer and non-neoplastic lung

DOE PAGES

Robinson, Lary A.; Jaing, Crystal J.; Campbell, Christine Pierce; ...

2016-07-14

Although ~20% of human cancers are caused by microorganisms, only suspicion exists for a microbial cause of lung cancer. Potential infectious agents were investigated in non-small cell lung cancer (NSCLC) and non-neoplastic lung. Seventy NSCLC tumours (33 squamous cell carcinomas, 17 adenocarcinomas, 10 adenocarcinomas with lepidic spread, and 10 oligometastases) and 10 non-neoplastic lung specimens were evaluated for molecular evidence of microorganisms. Tissues were subjected to the Lawrence Livermore Microbial Detection Array, an oncovirus panel of the International Agency for Research on Cancer, and human papillomavirus (HPV) genotyping. Associations were examined between microbial prevalence, clinical characteristics, and p16 and EGFRmore » expression. Retroviral DNA was observed in 85% squamous cell carcinomas, 47% adenocarcinomas, and 10% adenocarcinomas with lepidic spread. Human papillomavirus DNA was found in 69% of squamous cell carcinomas with 30% containing high-risk HPV types. No significant viral DNA was detected in non-neoplastic lung. Patients with tumours containing viral DNA experienced improved long-term survival compared with patients with viral DNA-negative tumours. Lastly, most squamous cell carcinomas and adenocarcinomas contained retroviral DNA and one-third of squamous cell carcinomas contained high-risk HPV DNA. Viral DNA was absent in non-neoplastic lung. Trial results encourage further study of the viral contribution to lung carcinogenesis.« less

Molecular evidence of viral DNA in non-small cell lung cancer and non-neoplastic lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robinson, Lary A.; Jaing, Crystal J.; Campbell, Christine Pierce

Although ~20% of human cancers are caused by microorganisms, only suspicion exists for a microbial cause of lung cancer. Potential infectious agents were investigated in non-small cell lung cancer (NSCLC) and non-neoplastic lung. Seventy NSCLC tumours (33 squamous cell carcinomas, 17 adenocarcinomas, 10 adenocarcinomas with lepidic spread, and 10 oligometastases) and 10 non-neoplastic lung specimens were evaluated for molecular evidence of microorganisms. Tissues were subjected to the Lawrence Livermore Microbial Detection Array, an oncovirus panel of the International Agency for Research on Cancer, and human papillomavirus (HPV) genotyping. Associations were examined between microbial prevalence, clinical characteristics, and p16 and EGFRmore » expression. Retroviral DNA was observed in 85% squamous cell carcinomas, 47% adenocarcinomas, and 10% adenocarcinomas with lepidic spread. Human papillomavirus DNA was found in 69% of squamous cell carcinomas with 30% containing high-risk HPV types. No significant viral DNA was detected in non-neoplastic lung. Patients with tumours containing viral DNA experienced improved long-term survival compared with patients with viral DNA-negative tumours. Lastly, most squamous cell carcinomas and adenocarcinomas contained retroviral DNA and one-third of squamous cell carcinomas contained high-risk HPV DNA. Viral DNA was absent in non-neoplastic lung. Trial results encourage further study of the viral contribution to lung carcinogenesis.« less

T Cells that Recognize HPV Protein Can Target Virus-Infected Cells | Center for Cancer Research

Cancer.gov

Adoptive T-cell transfer (ACT) is a promising form of cancer immunotherapy. Treating patients with T cells isolated from a tumor and subsequently expanded in the lab can cause the complete regression of some melanomas and cervical cancers, but the treatment is currently restricted to a few cancer types. An approach that may be applied to a wider array of cancers involves modifying peripheral blood T cells with chimeric antigen receptors or T-cell receptors (TCR) that target specific tumor antigens. Unfortunately, epithelial cancers, which are the vast majority of cancers diagnosed, have proven difficult to treat this way because most identified antigens are shared with healthy tissues and targeting them leads to toxic side effects. However, cancers caused by persistent human papillomavirus (HPV) infection, including cervical, head and neck, anal, vaginal, vulvar, and penile cancers, may be particularly amenable to the latter form of ACT since the E6 and E7 viral proteins are essential for cancer formation but are not produced in normal tissues. To test this idea, Christian Hinrichs, M.D., and his colleagues examined tumor infiltrating lymphocytes (TILs) from a patient who experienced a prolonged disease-free period after her second surgical removal of metastatic anal cancer in the hopes of identifying a TCR against one of the HPV oncoproteins.

Linear biocompatible glyco-polyamidoamines as dual action mode virus infection inhibitors with potential as broad-spectrum microbicides for sexually transmitted diseases

NASA Astrophysics Data System (ADS)

Mauro, Nicolò; Ferruti, Paolo; Ranucci, Elisabetta; Manfredi, Amedea; Berzi, Angela; Clerici, Mario; Cagno, Valeria; Lembo, David; Palmioli, Alessandro; Sattin, Sara

2016-09-01

The initial steps of viral infections are mediated by interactions between viral proteins and cellular receptors. Blocking the latter with high-affinity ligands may inhibit infection. DC-SIGN, a C-type lectin receptor expressed by immature dendritic cells and macrophages, mediates human immunodeficiency virus (HIV) infection by recognizing mannose clusters on the HIV-1 gp120 envelope glycoprotein. Mannosylated glycodendrimers act as HIV entry inhibitors thanks to their ability to block this receptor. Previously, an amphoteric, but prevailingly cationic polyamidoamine named AGMA1 proved effective as infection inhibitor for several heparan sulfate proteoglycan-dependent viruses, such as human papilloma virus HPV-16 and herpes simplex virus HSV-2. An amphoteric, but prevailingly anionic PAA named ISA23 proved inactive. It was speculated that the substitution of mannosylated units for a limited percentage of AGMA1 repeating units, while imparting anti-HIV activity, would preserve the fundamentals of its HPV-16 and HSV-2 infection inhibitory activity. In this work, four biocompatible linear PAAs carrying different amounts of mannosyl-triazolyl pendants, Man-ISA7, Man-ISA14, Man-AGMA6.5 and Man-AGMA14.5, were prepared by reaction of 2-(azidoethyl)-α-D-mannopyranoside and differently propargyl-substituted AGMA1 and ISA23. All mannosylated PAAs inhibited HIV infection. Both Man-AGMA6.5 and Man-AGMA14.5 maintained the HPV-16 and HSV-2 activity of the parent polymer, proving broad-spectrum, dual action mode virus infection inhibitors.

Comprehensive Analysis of DNA Methylation in Head and Neck Squamous Cell Carcinoma Indicates Differences by Survival and Clinicopathologic Characteristics

PubMed Central

Colacino, Justin A.; Dolinoy, Dana C.; Duffy, Sonia A.; Sartor, Maureen A.; Chepeha, Douglas B.; Bradford, Carol R.; McHugh, Jonathan B.; Patel, Divya A.; Virani, Shama; Walline, Heather M.; Bellile, Emily; Terrell, Jeffrey E.; Stoerker, Jay A.; Taylor, Jeremy M. G.; Carey, Thomas E.; Wolf, Gregory T.; Rozek, Laura S.

2013-01-01

Head and neck squamous cell carcinoma (HNSCC) is the eighth most commonly diagnosed cancer in the United States. The risk of developing HNSCC increases with exposure to tobacco, alcohol and infection with human papilloma virus (HPV). HPV-associated HNSCCs have a distinct risk profile and improved prognosis compared to cancers associated with tobacco and alcohol exposure. Epigenetic changes are an important mechanism in carcinogenic progression, but how these changes differ between viral- and chemical-induced cancers remains unknown. CpG methylation at 1505 CpG sites across 807 genes in 68 well-annotated HNSCC tumor samples from the University of Michigan Head and Neck SPORE patient population were quantified using the Illumina Goldengate Methylation Cancer Panel. Unsupervised hierarchical clustering based on methylation identified 6 distinct tumor clusters, which significantly differed by age, HPV status, and three year survival. Weighted linear modeling was used to identify differentially methylated genes based on epidemiological characteristics. Consistent with previous in vitro findings by our group, methylation of sites in the CCNA1 promoter was found to be higher in HPV(+) tumors, which was validated in an additional sample set of 128 tumors. After adjusting for cancer site, stage, age, gender, alcohol consumption, and smoking status, HPV status was found to be a significant predictor for DNA methylation at an additional 11 genes, including CASP8 and SYBL1. These findings provide insight into the epigenetic regulation of viral vs. chemical carcinogenesis and could provide novel targets for development of individualized therapeutic and prevention regimens based on environmental exposures. PMID:23358896

Comprehensive analysis of DNA methylation in head and neck squamous cell carcinoma indicates differences by survival and clinicopathologic characteristics.

PubMed

Colacino, Justin A; Dolinoy, Dana C; Duffy, Sonia A; Sartor, Maureen A; Chepeha, Douglas B; Bradford, Carol R; McHugh, Jonathan B; Patel, Divya A; Virani, Shama; Walline, Heather M; Bellile, Emily; Terrell, Jeffrey E; Stoerker, Jay A; Taylor, Jeremy M G; Carey, Thomas E; Wolf, Gregory T; Rozek, Laura S

2013-01-01

Head and neck squamous cell carcinoma (HNSCC) is the eighth most commonly diagnosed cancer in the United States. The risk of developing HNSCC increases with exposure to tobacco, alcohol and infection with human papilloma virus (HPV). HPV-associated HNSCCs have a distinct risk profile and improved prognosis compared to cancers associated with tobacco and alcohol exposure. Epigenetic changes are an important mechanism in carcinogenic progression, but how these changes differ between viral- and chemical-induced cancers remains unknown. CpG methylation at 1505 CpG sites across 807 genes in 68 well-annotated HNSCC tumor samples from the University of Michigan Head and Neck SPORE patient population were quantified using the Illumina Goldengate Methylation Cancer Panel. Unsupervised hierarchical clustering based on methylation identified 6 distinct tumor clusters, which significantly differed by age, HPV status, and three year survival. Weighted linear modeling was used to identify differentially methylated genes based on epidemiological characteristics. Consistent with previous in vitro findings by our group, methylation of sites in the CCNA1 promoter was found to be higher in HPV(+) tumors, which was validated in an additional sample set of 128 tumors. After adjusting for cancer site, stage, age, gender, alcohol consumption, and smoking status, HPV status was found to be a significant predictor for DNA methylation at an additional 11 genes, including CASP8 and SYBL1. These findings provide insight into the epigenetic regulation of viral vs. chemical carcinogenesis and could provide novel targets for development of individualized therapeutic and prevention regimens based on environmental exposures.

Multistatic Array Sampling Scheme for Fast Near-Field Image Reconstruction

DTIC Science & Technology

2016-01-01

reconstruction. The array topology samples the scene on a regular grid of phase centers, using a tiling of Boundary Arrays (BAs). Following a simple correction...hardware. Fig. 1 depicts the multistatic array topology. As seen, the topology is a tiled arrangement of Boundary Arrays (BAs). The BA is a well-known...sparse array layout comprised of two linear transmit arrays, and two linear receive arrays [6]. A slightly different tiled arrangement of BAs was used

The epigenetic landscape of oral squamous cell carcinoma

PubMed Central

Jithesh, P V; Risk, J M; Schache, A G; Dhanda, J; Lane, B; Liloglou, T; Shaw, R J

2013-01-01

Background: There is relatively little methylation array data available specifically for oral squamous cell carcinoma (OSCC). This study aims to compare the DNA methylome across a large cohort of tumour/normal pairs. Methods: DNA was extracted from 44 OSCCs and paired normal mucosa. DNA methylation analysis employed the Illumina GoldenGate high-throughput array comprising 1505 CpG loci selected from 807 epigenetically regulated genes. This data was correlated with extracapsular spread (ECS), human papilloma virus (HPV) status, recurrence and 5-year survival. Results: Differential methylation levels of a number of genes distinguished the tumour tissue sample from the matched normal. Putative methylation signatures for ECS and recurrence were identified. The concept of concordant methylation or CpG island methylator phenotype (CIMP) in OSCC is supported by our data, with an association between ‘CIMP-high' and worse prognosis. Epigenetic deregulation of NOTCH4 signalling in OSCC was also observed, as part of a possible methylation signature for recurrence, with parallels to recently discovered NOTCH mutations in HNSCC. Differences in methylation in HPV-driven cases were seen, but are less significant than that has been recently proposed in other series. Conclusion: Although OSCC seems as much an ‘epigenetic' as a genetic disease, the translational potential of cancer epigenetics has yet to be fully exploited. This data points to the application of epigenetic biomarkers and targets available to further the development of therapy in OSCC. PMID:23287992

Conformal array design on arbitrary polygon surface with transformation optics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deng, Li, E-mail: dengl@bupt.edu.cn; Hong, Weijun, E-mail: hongwj@bupt.edu.cn; Zhu, Jianfeng

2016-06-15

A transformation-optics based method to design a conformal antenna array on an arbitrary polygon surface is proposed and demonstrated in this paper. This conformal antenna array can be adjusted to behave equivalently as a uniformly spaced linear array by applying an appropriate transformation medium. An typical example of general arbitrary polygon conformal arrays, not limited to circular array, is presented, verifying the proposed approach. In summary, the novel arbitrary polygon surface conformal array can be utilized in array synthesis and beam-forming, maintaining all benefits of linear array.

Knowledge about human papillomavirus and prevention of cervical cancer among women of Arkhangelsk, Northwest Russia.

PubMed

Roik, Elena E; Sharashova, Ekaterina E; Nieboer, Evert; Kharkova, Olga A; Postoev, Vitaly A; Odland, Jon Ø

2017-01-01

Knowledge about cervical cancer (CC) risk factors and benefits of CC prevention motivates women to participate in its screening. However, several studies show that there is a significant knowledge deficit worldwide about human papillomavirus (HPV). The current study explores the level of knowledge about HPV and CC prevention in the context of sociodemographic and behavioral characteristics of women who visited an antenatal clinic in Arkhangelsk, Russia. This cross-sectional study was conducted in the city of Arkhangelsk, which seats the administrative center of Arkhangelsk County, Northwest Russia. It included women who consulted a gynecologist for any reason between January 1, 2015 and April 30, 2015, were residents of Arkhangelsk, 25 to 65 years of age and sexually active (N = 300). Student's t-test for continuous variables and Pearson's χ2 test for categorical variables were used in the comparisons of women grouped as having either poor or sufficient knowledge. Linear regression analysis was also employed. The level of knowledge about HPV and CC prevention was associated with education, parity, age of initiating of intercourse, and sources of information. After adjustment, women with university education were more likely to have higher knowledge about HPV and CC prevention compared to those with lower education. We observed that most participants had a sufficient level of knowledge. Educational gaps were identified that potentially could be used to tailor interventions in CC prevention.

Restoring Low Sidelobe Antenna Patterns with Failed Elements in a Phased Array Antenna

DTIC Science & Technology

2016-02-01

optimum low sidelobes are demonstrated in several examples. Index Terms — Array signal processing, beams, linear algebra , phased arrays, shaped...represented by a linear combination of low sidelobe beamformers with no failed elements, ’s, in a neighborhood around under the constraint that the linear ...would expect that linear combinations of them in a neighborhood around would also have low sidelobes. The algorithms in this paper exploit this

Diffuse optical measurements of head and neck tumor hemodynamics for early prediction of radiation therapy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Dong, Lixin; Kudrimoti, Mahesh; Irwin, Daniel; Chen, Li; Shang, Yu; Li, Xingzhe; Stevens, Scott D.; Shelton, Brent J.; Yu, Guoqiang

2016-03-01

Radiation therapy is a principal modality for head and neck cancers and its efficacy depends on tumor hemodynamics. Our laboratory developed a hybrid diffuse optical instrument allowing for simultaneous measurements of tumor blood flow and oxygenation. In this study, the clinically involved cervical lymph node was monitored by the hybrid instrument once a week over the treatment period of seven weeks. Based on treatment outcomes within one year, patients were classified into a complete response group (CR) and an incomplete response group (IR) with remote metastasis and/or local recurrence. A linear mixed models was used to compare tumor hemodynamic responses to the treatment between the two groups. Interestingly, we found that human papilloma virus (HPV-16) status largely affected tumor hemodynamic responses. For HPV-16 negative tumors, significant differences in blood flow index (BFI, p = 0.007) and reduced scattering coefficient (μs', p = 0.0005) were observed between the two groups; IR tumors exhibited higher μs' values and a continuous increase in BFI over the treatment period. For HPV-16 positive tumors, oxygenated hemoglobin concentration ([HbO2]) and blood oxygen saturation (StO2) were significant different (p = 0.003 and 0.01, respectively); IR group showed lower [HbO2] and StO2. Our results imply HPV-16 negative tumors with higher density of vasculature (μs') and higher blood flow show poor responses to radiotherapy and HPV-16 positive tumors with lower tissue oxygenation level (lower StO2 and [HbO2]) exhibit poor treatment outcomes. Our diffuse optical measurements show the great potential for early prediction of radiotherapy in head and neck cancers.

Compression dynamics of quasi-spherical wire arrays with different linear mass profiles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitrofanov, K. N., E-mail: mitrofan@triniti.ru; Aleksandrov, V. V.; Gritsuk, A. N.

Results of experimental studies of the implosion of quasi-spherical wire (or metalized fiber) arrays are presented. The goal of the experiments was to achieve synchronous three-dimensional compression of the plasma produced in different regions of a quasi-spherical array into its geometrical center. To search for optimal synchronization conditions, quasi-spherical arrays with different initial profiles of the linear mass were used. The following dependences of the linear mass on the poloidal angle were used: m{sub l}(θ) ∝ sin{sup –1}θ and m{sub l}(θ) ∝ sin{sup –2}θ. The compression dynamics of such arrays was compared with that of quasi-spherical arrays without linear massmore » profiling, m{sub l}(θ) = const. To verify the experimental data, the spatiotemporal dynamics of plasma compression in quasi-spherical arrays was studied using various diagnostics. The experiments on three-dimensional implosion of quasi-spherical arrays made it possible to study how the frozen-in magnetic field of the discharge current penetrates into the array. By measuring the magnetic field in the plasma of a quasi-spherical array, information is obtained on the processes of plasma production and formation of plasma flows from the wire/fiber regions with and without an additionally deposited mass. It is found that penetration of the magnetic flux depends on the initial linear mass profile m{sub l}(θ) of the quasi-spherical array. From space-resolved spectral measurements and frame imaging of plasma X-ray emission, information is obtained on the dimensions and shape of the X-ray source formed during the implosion of a quasi-spherical array. The intensity of this source is estimated and compared with that of the Z-pinch formed during the implosion of a cylindrical array.« less

3D morphology reconstruction using linear array CCD binocular stereo vision imaging system

NASA Astrophysics Data System (ADS)

Pan, Yu; Wang, Jinjiang

2018-01-01

Binocular vision imaging system, which has a small field of view, cannot reconstruct the 3-D shape of the dynamic object. We found a linear array CCD binocular vision imaging system, which uses different calibration and reconstruct methods. On the basis of the binocular vision imaging system, the linear array CCD binocular vision imaging systems which has a wider field of view can reconstruct the 3-D morphology of objects in continuous motion, and the results are accurate. This research mainly introduces the composition and principle of linear array CCD binocular vision imaging system, including the calibration, capture, matching and reconstruction of the imaging system. The system consists of two linear array cameras which were placed in special arrangements and a horizontal moving platform that can pick up objects. The internal and external parameters of the camera are obtained by calibrating in advance. And then using the camera to capture images of moving objects, the results are then matched and 3-D reconstructed. The linear array CCD binocular vision imaging systems can accurately measure the 3-D appearance of moving objects, this essay is of great significance to measure the 3-D morphology of moving objects.

Linear encoding device

NASA Technical Reports Server (NTRS)

Leviton, Douglas B. (Inventor)

1993-01-01

A Linear Motion Encoding device for measuring the linear motion of a moving object is disclosed in which a light source is mounted on the moving object and a position sensitive detector such as an array photodetector is mounted on a nearby stationary object. The light source emits a light beam directed towards the array photodetector such that a light spot is created on the array. An analog-to-digital converter, connected to the array photodetector is used for reading the position of the spot on the array photodetector. A microprocessor and memory is connected to the analog-to-digital converter to hold and manipulate data provided by the analog-to-digital converter on the position of the spot and to compute the linear displacement of the moving object based upon the data from the analog-to-digital converter.

A Fourier Method for Sidelobe Reduction in Equally Spaced Linear Arrays

NASA Astrophysics Data System (ADS)

Safaai-Jazi, Ahmad; Stutzman, Warren L.

2018-04-01

Uniformly excited, equally spaced linear arrays have a sidelobe level larger than -13.3 dB, which is too high for many applications. This limitation can be remedied by nonuniform excitation of array elements. We present an efficient method for sidelobe reduction in equally spaced linear arrays with low penalty on the directivity. The method involves the following steps: construction of a periodic function containing only the sidelobes of the uniformly excited array, calculation of the Fourier series of this periodic function, subtracting the series from the array factor of the original uniformly excited array after it is truncated, and finally mitigating the truncation effects which yields significant increase in sidelobe level reduction. A sidelobe reduction factor is incorporated into element currents that makes much larger sidelobe reductions possible and also allows varying the sidelobe level incrementally. It is shown that such newly formed arrays can provide sidelobe levels that are at least 22.7 dB below those of the uniformly excited arrays with the same size and number of elements. Analytical expressions for element currents are presented. Radiation characteristics of the sidelobe-reduced arrays introduced here are examined, and numerical results for directivity, sidelobe level, and half-power beam width are presented for example cases. Performance improvements over popular conventional array synthesis methods, such as Chebyshev and linear current tapered arrays, are obtained with the new method.

Human Papilloma Virus-Dependent HMGA1 Expression Is a Relevant Step in Cervical Carcinogenesis1

PubMed Central

Mellone, Massimiliano; Rinaldi, Christian; Massimi, Isabella; Petroni, Marialaura; Veschi, Veronica; Talora, Claudio; Truffa, Silvia; Stabile, Helena; Frati, Luigi; Screpanti, Isabella; Gulino, Alberto; Giannini, Giuseppe

2008-01-01

HMGA1 is a member of a small family of architectural transcription factors involved in the coordinate assembly of multiprotein complexes referred to as enhanceosomes. In addition to their role in cell proliferation, differentiation, and development, high-mobility group proteins of the A type (HMGA) family members behave as transforming protoncogenes either in vitro or in animal models. Recent reports indicated that HMGA1 might counteract p53 pathway and provided an interesting hint on the mechanisms determining HMGA's transforming potential. HMGA1 expression is deregulated in a very large array of human tumors, including cervical cancer, but very limited information is available on the molecular mechanisms leading to HMGA1 deregulation in cancer cells. Here, we report that HMGA1 expression is sustained by human papilloma virus (HPV) E6/E7 proteins in cervical cancer, as demonstrated by either E6/E7 overexpression or by repression through RNA interference. Knocking down HMGA1 expression by means of RNA interference, we also showed that it is involved in cell proliferation and contributes to p53 inactivation in this type of neoplasia. Finally, we show that HMGA1 is necessary for the full expression of HPV18 E6 and E7 oncoproteins thus establishing a positive autoregulatory loop between HPV E6/E7 and HMGA1 expression. PMID:18670638

Advances in diagnostic ultrasonography.

PubMed

Reef, V B

1991-08-01

A wide variety of ultrasonographic equipment currently is available for use in equine practice, but no one machine is optimal for every type of imaging. Image quality is the most important factor in equipment selection once the needs of the practitioner are ascertained. The transducer frequencies available, transducer footprints, depth of field displayed, frame rate, gray scale, simultaneous electrocardiography, Doppler, and functions to modify the image are all important considerations. The ability to make measurements off of videocassette recorder playback and future upgradability should be evaluated. Linear array and sector technology are the backbone of equine ultrasonography today. Linear array technology is most useful for a high-volume broodmare practice, whereas sector technology is ideal for a more general equine practice. The curved or convex linear scanner has more applications than the standard linear array and is equipped with the linear array rectal probe, which provides the equine practitioner with a more versatile unit for equine ultrasonographic evaluations. The annular array and phased array systems have improved image quality, but each has its own limitations. The new sector scanners still provide the most versatile affordable equipment for equine general practice.

The impact and cost-effectiveness of nonavalent HPV vaccination in the United States: Estimates from a simplified transmission model.

PubMed

Chesson, Harrell W; Markowitz, Lauri E; Hariri, Susan; Ekwueme, Donatus U; Saraiya, Mona

2016-06-02

The objective of this study was to assess the incremental costs and benefits of the 9-valent HPV vaccine (9vHPV) compared with the quadrivalent HPV vaccine (4vHPV). Like 4vHPV, 9vHPV protects against HPV types 6, 11, 16, and 18. 9vHPV also protects against 5 additional HPV types 31, 33, 45, 52, and 58. We adapted a previously published model of the impact and cost-effectiveness of 4vHPV to include the 5 additional HPV types in 9vHPV. The vaccine strategies we examined were (1) 4vHPV for males and females; (2) 9vHPV for females and 4vHPV for males; and (3) 9vHPV for males and females. In the base case, 9vHPV cost $13 more per dose than 4vHPV, based on available vaccine price information. Providing 9vHPV to females compared with 4vHPV for females (assuming 4vHPV for males in both scenarios) was cost-saving regardless of whether or not cross-protection for 4vHPV was assumed. The cost per quality-adjusted life year (QALY) gained by 9vHPV for both sexes (compared with 4vHPV for both sexes) was < $0 (cost-saving) when assuming no cross-protection for 4vHPV and $8,600 when assuming cross-protection for 4vHPV. Compared with a vaccination program of 4vHPV for both sexes, a vaccination program of 9vHPV for both sexes can improve health outcomes and can be cost-saving.

HPV vaccine

MedlinePlus

... HPV; Gardasil; HPV2; HPV4; Vaccine to prevent cervical cancer; Genital warts - HPV vaccine; Cervical dysplasia - HPV vaccine; Cervical cancer - HPV vaccine; Cancer of the cervix - HPV vaccine; ...

Modulation Transfer Function (MTF) measurement techniques for lenses and linear detector arrays

NASA Technical Reports Server (NTRS)

Schnabel, J. J., Jr.; Kaishoven, J. E., Jr.; Tom, D.

1984-01-01

Application is the determination of the Modulation Transfer Function (MTF) for linear detector arrays. A system set up requires knowledge of the MTF of the imaging lens. Procedure for this measurement is described for standard optical lab equipment. Given this information, various possible approaches to MTF measurement for linear arrays is described. The knife edge method is then described in detail.

A comparison of the MeltPro® HPV Test with the Cobas® HPV Test for detecting and genotyping 14 high-risk human papillomavirus types.

PubMed

Tang, Zhiteng; Xu, Ye; Song, Najie; Zou, Dongqing; Liao, Yiqun; Li, Qingge; Pan, Chao

2018-03-01

The clinical performance of the newly developed MeltPro ® HPV Test, based on multicolor melting curve analysis, was evaluated and compared with the commercially available Cobas ® HPV Test for detection of HPV and genotyping of HPV-16 and HPV-18. A total of 1647 cervical samples were analyzed with both tests. The agreement values were 96.2% for HPV detection, 99.6% for HPV-16 identification, and 99.7% for HPV-18 identification. All genotyping results from MeltPro ® HPV Test showed that HPV-52, HPV-58, and HPV-16 were the most common types in this study. Intra-laboratory reproducibility studies showed 97.8% agreement while inter-laboratory reproducibility studies showed 96.9% agreement for the MeltPro ® HPV Test. The MeltPro ® HPV Test and Cobas ® HPV Test are highly correlative and are useful for monitoring HPV infection.

CLDN1 expression in cervical cancer cells is related to tumor invasion and metastasis.

PubMed

Zhang, Wei-Na; Li, Wei; Wang, Xiao-Li; Hu, Zheng; Zhu, Da; Ding, Wen-Cheng; Liu, Dan; Li, Ke-Zhen; Ma, Ding; Wang, Hui

2016-12-27

Even though infection with human papillomaviruses (HPV) is very important, it is not the sole cause of cervical cancer. Because it is known that genetic variations that result from HPV infection are probably the most important causes of cervical cancer, we used human whole genome array comparative genomic hybridization to detect the copy number variations of genes in cervical squamous cell carcinoma. The results of the array were validated by PCR, FISH and immunohistochemistry. We find that the copy number and protein expression of claudin-1 (CLDN1) increase with the progression of cervical cancer. The strong positive staining of CLDN1 in the cervical lymph node metastasis group received a significantly higher score than the staining in the group with no lymph node metastasis of cervical cancer tissues. The overexpression of CLDN1 in SiHa cells can increase anti-apoptosis ability and promote invasive ability of these cells accompanied by a decrease in expression of the epithelial marker E-cadherin as well as an increase in the expression of the mesenchymal marker vimentin. CLDN1 induces the epithelial-mesenchymal transition (EMT) through its interaction with SNAI1. Furthermore, we demonstrate that CLDN1 overexpression has significant effects on the growth and metastasis of xenografted tumors in athymic mice. These data suggest that CLDN1 promotes invasion and metastasis in cervical cancer cells via the expression of EMT/invasion-related genes. Therefore, CLDN1 could be a potential therapeutic target for the treatment of cervical cancer.

Application of linear array imaging techniques to the real-time inspection of airframe structures and substructures

NASA Technical Reports Server (NTRS)

Miller, James G.

1995-01-01

Development and application of linear array imaging technologies to address specific aging-aircraft inspection issues is described. Real-time video-taped images were obtained from an unmodified commercial linear-array medical scanner of specimens constructed to simulate typical types of flaws encountered in the inspection of aircraft structures. Results suggest that information regarding the characteristics, location, and interface properties of specific types of flaws in materials and structures may be obtained from the images acquired with a linear array. Furthermore, linear array imaging may offer the advantage of being able to compare 'good' regions with 'flawed' regions simultaneously, and in real time. Real-time imaging permits the inspector to obtain image information from various views and provides the opportunity for observing the effects of introducing specific interventions. Observation of an image in real-time can offer the operator the ability to 'interact' with the inspection process, thus providing new capabilities, and perhaps, new approaches to nondestructive inspections.

Comparison of characteristics and downstream uniformity of linear-field and cross-field atmospheric pressure plasma jet array in He

NASA Astrophysics Data System (ADS)

Zhang, Bo; Fang, Zhi; Liu, Feng; Zhou, Renwu; Zhou, Ruoyu

2018-06-01

Using an atmospheric pressure plasma jet array is an effective way for expanding the treatment area of a single jet, and generating arrays with well downstream uniformity is of great interest for its applications. In this paper, a plasma jet array in helium is generated in a linear-field jet array with a ring-ring electrode structure excited by alternating current. The characteristics and downstream uniformity of the array and their dependence on the applied voltage and gas flow rate are investigated through optical, electrical, and Schlieren diagnostics. The results are compared with those of our reported work of a cross-field jet array with a needle-ring electrode structure. The results show that the linear-field jet array can generate relatively large-scale plasma with better uniformity and longer plumes than the cross-field case. The divergences observed in gas channels and the plasma plume trajectories are much less than those of the cross-field one. The deflection angle of lateral plumes is less than 6°, which is independent of the gas flow rate and applied voltage. The maximum downstream plumes of 23 mm can be obtained at 7 kV peak applied voltage and 4 l/min gas flow rate. The better uniformity of linear-field jet arrays is due to the effective suppression of hydrodynamic and electrical interactions among the jets in the arrays with a more uniform electric field distribution. The hydrodynamic interaction induced by the gas heating in the linear-field jet array is less than that of the cross-field one. The more uniform electric field distribution in the linear-field jet arrays can reduce the divergence of the propagation trajectories of the plasma plumes. It will generate less residual charge between the adjacent discharges and thus can reduce the accumulation effect of Coulomb force between the plasma plumes. The reported results can help design controllable and scalable plasma jet arrays with well uniformity for material surface and biomedical treatments.

Nationwide Survey of Knowledge and Health Beliefs regarding Human Papillomavirus among HPV-Vaccinated Female Students in Malaysia

PubMed Central

Wong, Li Ping; Raja Muhammad Yusoff, Raja Nur Amalina; Edib, Zobaida; Sam, I-Ching; Zimet, Gregory D.

2016-01-01

The National HPV Immunization Programme, which offers free human papillomavirus (HPV) vaccines to teenaged female students, was launched in Malaysia in 2010. HPV vaccination paired with adequate knowledge about HPV infection provides the best protection against cervical cancer. To identify the level of knowledge and the health beliefs towards HPV and the HPV vaccine among HPV-vaccinated female students in Malaysia. A nationwide cross-sectional survey among 14 years old female students who had received three doses of the HPV vaccine was conducted in 32 randomly selected schools from 13 states and 3 federal territories in Malaysia between February 2013 and April 2013. Among 2482 respondents, knowledge about HPV infection and the HPV vaccine was extremely poor. The mean total knowledge score was only 3.56 (SD ± 1.76), out of a possible score of 10. The majority of respondents were unaware that vaccinating boys with HPV can help protect girls against HPV infection (91.6%), HPV cannot be cured (81.6%) and that HPV is a sexually transmitted infection (70.3%). Most of the respondents had the misconception that only females get HPV (95.1%), and that the HPV vaccine eliminates the need for Pap smear tests (68.3%). Most respondents (91.6%) believed that they would not get an HPV infection. Almost half of the respondents (42.9%) held the misconception that HPV infection could not lead to serious illness. Findings revealed poor knowledge about both HPV and the HPV vaccine, low perceived susceptibility to HPV infection and misinformation about HPV infection among HPV-vaccinated girls. Therefore, it is essential to increase the knowledge and awareness of health risks regarding HPV infection among teenaged girls who have received the HPV vaccine. PMID:27656876

Nationwide Survey of Knowledge and Health Beliefs regarding Human Papillomavirus among HPV-Vaccinated Female Students in Malaysia.

PubMed

Wong, Li Ping; Raja Muhammad Yusoff, Raja Nur Amalina; Edib, Zobaida; Sam, I-Ching; Zimet, Gregory D

The National HPV Immunization Programme, which offers free human papillomavirus (HPV) vaccines to teenaged female students, was launched in Malaysia in 2010. HPV vaccination paired with adequate knowledge about HPV infection provides the best protection against cervical cancer. To identify the level of knowledge and the health beliefs towards HPV and the HPV vaccine among HPV-vaccinated female students in Malaysia. A nationwide cross-sectional survey among 14 years old female students who had received three doses of the HPV vaccine was conducted in 32 randomly selected schools from 13 states and 3 federal territories in Malaysia between February 2013 and April 2013. Among 2482 respondents, knowledge about HPV infection and the HPV vaccine was extremely poor. The mean total knowledge score was only 3.56 (SD ± 1.76), out of a possible score of 10. The majority of respondents were unaware that vaccinating boys with HPV can help protect girls against HPV infection (91.6%), HPV cannot be cured (81.6%) and that HPV is a sexually transmitted infection (70.3%). Most of the respondents had the misconception that only females get HPV (95.1%), and that the HPV vaccine eliminates the need for Pap smear tests (68.3%). Most respondents (91.6%) believed that they would not get an HPV infection. Almost half of the respondents (42.9%) held the misconception that HPV infection could not lead to serious illness. Findings revealed poor knowledge about both HPV and the HPV vaccine, low perceived susceptibility to HPV infection and misinformation about HPV infection among HPV-vaccinated girls. Therefore, it is essential to increase the knowledge and awareness of health risks regarding HPV infection among teenaged girls who have received the HPV vaccine.

Linearly tapered slot antenna circular array for mobile communications

NASA Technical Reports Server (NTRS)

Simons, Rainee N.; Kelly, Eron; Lee, Richard Q.; Taub, Susan R.

1993-01-01

The design, fabrication and testing of a conformal K-band circular array is presented. The array consists of sixteen linearly tapered slot antennas (LTSA). It is fed by a 1:16 microstrip line power splitter via electromagnetic coupling. The array has an omni-directional pattern in the azimuth plane. In the elevation plane the beam is displaced above the horizon.

A phase III clinical study to compare the immunogenicity and safety of the 9-valent and quadrivalent HPV vaccines in men.

PubMed

Van Damme, Pierre; Meijer, Chris J L M; Kieninger, Dorothee; Schuyleman, Anne; Thomas, Stephane; Luxembourg, Alain; Baudin, Martine

2016-07-29

A nine-valent human papilloma virus (9vHPV) vaccine has been developed to prevent infections and diseases related to HPV 6/11/16/18 (as per the licensed quadrivalent HPV (qHPV) vaccine) as well as to five additional oncogenic HPV types (HPV 31/33/45/52/58). The 9vHPV vaccine has the potential to prevent 90% of cervical cancers, HPV-related anal, vaginal and vulval cancers and anogenital warts. We compared the immunogenicity and safety of the 9vHPV vaccine versus the qHPV vaccine in 16-26-year-old men. Participants (N=500) were randomised to receive 9vHPV or qHPV vaccines on day 1, month 2 and month 6. Serology testing was performed on day 1 and month 7. HPV type-specific antibody titres (anti-HPV 6/11/16/18/31/33/45/52/58) were determined by competitive Luminex immunoassay and expressed as geometric mean titres and seroconversion rates. Vaccine safety was also assessed. The HPV 6/11/16/18 immune responses elicited by the 9vHPV vaccine were comparable with those elicited by the qHPV vaccine. All participants receiving the 9vHPV vaccine seroconverted for HPV 31/33/45/52/58. The 9vHPV and qHPV vaccines showed comparable safety profiles. In addition to immune responses to HPV 31/33/45/52/58, a three-dose regimen of the 9vHPV vaccine elicited a similar immune response to HPV 6/11/16/18 when compared with the qHPV vaccine in men aged 16-26years. The safety profile was also similar for the two vaccines. The results from this study support extending the efficacy findings with qHPV vaccine to 9vHPV vaccine in men aged 16-26years. NCT02114385. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Detection and typing of low-risk human papillomavirus genotypes HPV 6, HPV 11, HPV 42, HPV 43 and HPV 44 by polymerase chain reaction and restriction fragment length polymorphism.

PubMed

Maver, Polona J; Poljak, Mario; Seme, Katja; Kocjan, Bostjan J

2010-10-01

A novel PCR-restriction fragment length polymorphism assay (PCR-RFLP) was developed for sensitive detection and reliable differentiation of five low-risk human papillomavirus (lr-HPV) genotypes: HPV 6, HPV 11, HPV 42, HPV 43 and HPV 44, as well as differentiation of prototypic and non-prototypic HPV 6 genomic variants. The assay is based on the amplification of a 320-bp fragment of the HPV E1 gene and subsequent analysis of PCR-products with BsaJI and HinFI. Testing on plasmid standards showed that PCR-RFLP enabled simple and reliable identification and differentiation of five targeted lr-HPV genotypes and could detect reproducibly down to 10 copies of viral genome equivalents per PCR. The PCR-RFLP showed almost complete agreement with previously obtained genotyping results on 42 HPV-DNA negative samples and 223 HPV-DNA positive samples (45 HPV 6, 34 HPV 11, 35 HPV 42, 10 HPV 43, 24 HPV 44 positive samples and 75 samples containing 28 non-targeted HPV genotypes). The novel assay is simple and robust, does not require any sophisticated equipment and can be of great value for epidemiological studies, particularly in settings in which financial resources are limited. Copyright (c) 2010 Elsevier B.V. All rights reserved.

A linear refractive photovoltaic concentrator solar array flight experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, P.A.; Murphy, D.M.; Piszczor, M.F.

1995-12-31

Concentrator arrays deliver a number of generic benefits for space including high array efficiency, protection from space radiation effects, and minimized plasma interactions. The line focus concentrator concept delivers two added advantages: (1) low-cost mass production of the lens material and, (2) relaxation of precise array tracking requirements to only a single axis. New array designs emphasize lightweight, high stiffness, stow-ability and ease of manufacture and assembly. The linear refractive concentrator can be designed to provide an essentially flat response over a wide range of longitudinal pointing errors for satellites having only single-axis tracking capability. In this paper the authorsmore » address the current status of the SCARLET linear concentrator program with special emphasis on hardware development of an array-level linear refractive concentrator flight experiment. An aggressive, 6-month development and flight validation program, sponsored by the Ballistic Missile Defense Organization (BMDO) and NASA Lewis Research Center, will quantify and verify SCARLET benefits with in-orbit performance measurements.« less

Off-Grid Direction of Arrival Estimation Based on Joint Spatial Sparsity for Distributed Sparse Linear Arrays

PubMed Central

Liang, Yujie; Ying, Rendong; Lu, Zhenqi; Liu, Peilin

2014-01-01

In the design phase of sensor arrays during array signal processing, the estimation performance and system cost are largely determined by array aperture size. In this article, we address the problem of joint direction-of-arrival (DOA) estimation with distributed sparse linear arrays (SLAs) and propose an off-grid synchronous approach based on distributed compressed sensing to obtain larger array aperture. We focus on the complex source distribution in the practical applications and classify the sources into common and innovation parts according to whether a signal of source can impinge on all the SLAs or a specific one. For each SLA, we construct a corresponding virtual uniform linear array (ULA) to create the relationship of random linear map between the signals respectively observed by these two arrays. The signal ensembles including the common/innovation sources for different SLAs are abstracted as a joint spatial sparsity model. And we use the minimization of concatenated atomic norm via semidefinite programming to solve the problem of joint DOA estimation. Joint calculation of the signals observed by all the SLAs exploits their redundancy caused by the common sources and decreases the requirement of array size. The numerical results illustrate the advantages of the proposed approach. PMID:25420150

Comparison of the Abbott RealTime High Risk HPV test and the Roche cobas 4800 HPV test using urine samples.

PubMed

Lim, Myong Cheol; Lee, Do-Hoon; Hwang, Sang-Hyun; Hwang, Na Rae; Lee, Bomyee; Shin, Hye Young; Jun, Jae Kwan; Yoo, Chong Woo; Lee, Dong Ock; Seo, Sang-Soo; Park, Sang-Yoon; Joo, Jungnam

2017-05-01

Human papillomavirus (HPV) testing based on cervical samples is important for use in cervical cancer screening. However, cervical sampling is invasive. Therefore, non-invasive methods for detecting HPV, such as urine samples, are needed. For HPV detection in urine samples, two real-time PCR (RQ-PCR) tests, Roche cobas 4800 test (Roche_HPV; Roche Molecular Diagnostics) and Abbott RealTime High Risk HPV test (Abbott_HPV; Abbott Laboratories) were compared to standard cervical samples. The performance of Roche_HPV and Abbott_HPV for HPV detection was evaluated at the National Cancer Center using 100 paired cervical and urine samples. The tests were also compared using urine samples stored at various temperatures and for a range of durations. The overall agreement between the Roche_HPV and Abbott_HPV tests using urine samples for any hrHPV type was substantial (86.0% with a kappa value of 0.7173), and that for HPV 16/18 was nearly perfect (99.0% with a kappa value of 0.9668). The relative sensitivities (based on cervical samples) for HPV 16/18 detection using Roche_HPV and Abbott_HPV with urine samples were 79.2% (95% CI; 57.9-92.9%) and 81.8% (95% CI; 59.7-94.8%), respectively. When the cut-off C T value for Abbott_HPV was extended to 40 for urine samples, the relative sensitivity of Abbott_HPV increased to 91.7% from 81.8% for HPV16/18 detection and to 87.0% from 68.5% for other hrHPV detection. The specificity was not affected by the change in the C T threshold. Roche_HPV and Abbott_HPV showed high concordance. However, HPV DNA detection using urine samples was inferior to HPV DNA detection using cervical samples. Interestingly, when the cut-off C T value was set to 40, Abbott_HPV using urine samples showed high sensitivity and specificity, comparable to those obtained using cervical samples. Fully automated DNA extraction and detection systems, such as Roche_HPV and Abbott_HPV, could reduce the variability in HPV detection and accelerate the standardization of HPV detection in urine. Thus, urine samples may be an effective alternative for HPV detection in women who hesitate to participate in cervical cancer screening programs. Copyright © 2017 Elsevier B.V. All rights reserved.

Micro-machined high-frequency (80 MHz) PZT thick film linear arrays.

PubMed

Zhou, Qifa; Wu, Dawei; Liu, Changgeng; Zhu, Benpeng; Djuth, Frank; Shung, K

2010-10-01

This paper presents the development of a micromachined high-frequency linear array using PZT piezoelectric thick films. The linear array has 32 elements with an element width of 24 μm and an element length of 4 mm. Array elements were fabricated by deep reactive ion etching of PZT thick films, which were prepared from spin-coating of PZT sol-gel composite. Detailed fabrication processes, especially PZT thick film etching conditions and a novel transferring-and-etching method, are presented and discussed. Array designs were evaluated by simulation. Experimental measurements show that the array had a center frequency of 80 MHz and a fractional bandwidth (-6 dB) of 60%. An insertion loss of -41 dB and adjacent element crosstalk of -21 dB were found at the center frequency.

Human papilloma virus (HPV) genotypes prevalence in a region of South Italy (Apulia).

PubMed

Coscia, Maria Franca; Monno, Rosa; Ballini, Andrea; Mirgaldi, Rosanna; Dipalma, Gianna; Pettini, Francesco; Cristallo, Vincenzo; Inchingolo, Francesco; Foti, Caterina; de Vito, Danila

2015-01-01

Since human papillomavirus (HPV) is the central casual factor in cervical cancer, understanding the epidemiology and geographical area distribution of the most prevalent HPV genotypes constitutes an important step towards development of strategies of prevention. The aim of this study was to investigate the prevalence of HPV infection and to determine HPV types distribution among 822 HPV positive women and some sexual male partners in Apulia (Italy). HPV DNA detection and genotyping was performed by nested-PCR for the L1 region and reverse line blot hybridization allowing the specific detection of 24 HPV genotyping both high risk (HR) and low risk (LR). The most prevalent HPV genotypes were HPV 16 (35%), HPV 31 (16%) HPV 6 (9%), HPV 58 and 66 (7%), followed by HPV 33 (6%), HPV 18 and 56 (4%), HPV 70 and 45 (3%), HPV 53 and 11 (2%). Currently 1.5% of tested specimens remained unclassified. Multiple infections with at last two different high- risk HPV genotypes were observed in 10% of specimens. This finding adds knowledge to HPV epidemiological investigation, and addresses further studies aimed to consider public health for identifying groups at risk for cervical cancer.

Model-based estimates of long-term persistence of induced HPV antibodies: a flexible subject-specific approach.

PubMed

Aregay, Mehreteab; Shkedy, Ziv; Molenberghs, Geert; David, Marie-Pierre; Tibaldi, Fabián

2013-01-01

In infectious diseases, it is important to predict the long-term persistence of vaccine-induced antibodies and to estimate the time points where the individual titers are below the threshold value for protection. This article focuses on HPV-16/18, and uses a so-called fractional-polynomial model to this effect, derived in a data-driven fashion. Initially, model selection was done from among the second- and first-order fractional polynomials on the one hand and from the linear mixed model on the other. According to a functional selection procedure, the first-order fractional polynomial was selected. Apart from the fractional polynomial model, we also fitted a power-law model, which is a special case of the fractional polynomial model. Both models were compared using Akaike's information criterion. Over the observation period, the fractional polynomials fitted the data better than the power-law model; this, of course, does not imply that it fits best over the long run, and hence, caution ought to be used when prediction is of interest. Therefore, we point out that the persistence of the anti-HPV responses induced by these vaccines can only be ascertained empirically by long-term follow-up analysis.

Calibration of the dietary data obtained from the Brazilian center of the Natural History of HPV Infection in Men study: the HIM Study.

PubMed

Teixeira, Juliana Araujo; Baggio, Maria Luiza; Fisberg, Regina Mara; Marchioni, Dirce Maria Lobo

2010-12-01

The objective of this study was to estimate the regressions calibration for the dietary data that were measured using the quantitative food frequency questionnaire (QFFQ) in the Natural History of HPV Infection in Men: the HIM Study in Brazil. A sample of 98 individuals from the HIM study answered one QFFQ and three 24-hour recalls (24HR) at interviews. The calibration was performed using linear regression analysis in which the 24HR was the dependent variable and the QFFQ was the independent variable. Age, body mass index, physical activity, income and schooling were used as adjustment variables in the models. The geometric means between the 24HR and the calibration-corrected QFFQ were statistically equal. The dispersion graphs between the instruments demonstrate increased correlation after making the correction, although there is greater dispersion of the points with worse explanatory power of the models. Identification of the regressions calibration for the dietary data of the HIM study will make it possible to estimate the effect of the diet on HPV infection, corrected for the measurement error of the QFFQ.

Linear antenna array optimization using flower pollination algorithm.

PubMed

Saxena, Prerna; Kothari, Ashwin

2016-01-01

Flower pollination algorithm (FPA) is a new nature-inspired evolutionary algorithm used to solve multi-objective optimization problems. The aim of this paper is to introduce FPA to the electromagnetics and antenna community for the optimization of linear antenna arrays. FPA is applied for the first time to linear array so as to obtain optimized antenna positions in order to achieve an array pattern with minimum side lobe level along with placement of deep nulls in desired directions. Various design examples are presented that illustrate the use of FPA for linear antenna array optimization, and subsequently the results are validated by benchmarking along with results obtained using other state-of-the-art, nature-inspired evolutionary algorithms such as particle swarm optimization, ant colony optimization and cat swarm optimization. The results suggest that in most cases, FPA outperforms the other evolutionary algorithms and at times it yields a similar performance.

Out-Phased Array Linearized Signaling (OPALS): A Practical Approach to Physical Layer Encryption

DTIC Science & Technology

2015-10-26

Out-Phased Array Linearized Signaling ( OPALS ): A Practical Approach to Physical Layer Encryption Eric Tollefson, Bruce R. Jordan Jr., and Joseph D... OPALS ) which provides a practical approach to physical-layer encryption through spatial masking. Our approach modifies just the transmitter to employ...of the channel. With Out-Phased Array Linearized Signaling ( OPALS ), we propose a new masking technique that has some advantages of each of the

Comparisons of VLP-Based ELISA, Neutralization Assays with Native HPV, and Neutralization Assays with PsV in Detecting HPV Antibody Responses in HIV-Infected Women

PubMed Central

Du, Ping; Brendle, Sarah; Milici, Janice; Camacho, Fabian; Zurlo, John; Christensen, Neil; Meyers, Craig

2015-01-01

Objective Human papillomavirus (HPV)-associated cancers are important public health problems in HIV-infected people. Assays based on HPV virus-like particles (VLP) and pseudoviruses (PsV) are commonly used to examine HPV antibody responses in HIV-infected people, but neutralization assays with native HPV have not been utilized and a comparison of these three assays is lacking. We evaluated the agreement of assays using VLP, native HPV and PsV in detecting HPV16 and 18 antibodies in HIV-infected women. Methods The VLP-based ELISA (VLP-ELISA) was used to detect antibody responses to HPV16 and 18 and cottontail rabbit papillomavirus (CRPV) VLP antigens. Neutralization assays with native HPV (NA-HPV) and with PsV (NA-PsV) were conducted to examine HPV16 or 18 neutralizing antibodies. Intra class correlation coefficients (ICC) and kappa coefficients were used to assess the agreements of seropositivity between the assays. Results The seroprevalence detected by the VLP-ELISA, NA-HPV and NA-PsV in 94 HIV-infected women was 35%, 51% and 27% for HPV16 and 14%, 44% and 21% for HPV18. Cross-reactivity between HPV16 and HPV18 was 0.35, 0.04 and 0.33 (kappa coefficients) for the VLP-ELISA, NA-HPV and NA-PsV. The agreements of seropositivity between the three assays were low. Six women who were HPV16 DNA positive were seropositive by the NA-HPV but only two were HPV16 seropositive by the VLP-ELISA or NA-PsV. One HPV18 DNA positive woman was seropositive by all three assays. Repeated tests indicated excellent reproducibility of the NA-HPV. Conclusion HPV serology results vary across different assays. The NA-HPV appears to be a sensitive and reliable approach in detecting natural HPV antibodies in HIV-infected women. The NA-HPV can be applied in both HPV natural history studies and vaccine studies in HIV-infected people. PMID:26085957

Attitudes towards Human Papilloma Virus Vaccination in the Latin American Andean Region.

PubMed

Nwanodi, Oroma

2017-09-08

This commentary explores the distribution of human papilloma virus (HPV) and HPV-related diseases, and factors affecting attitudes towards HPV, HPV-related diseases, and HPV vaccination in the Latin American Andean region. Lack of knowledge of HPV, known negative attitudes or incorrect assumptions about HPV, HPV-related diseases, and HPV vaccination provide a basis upon which to develop targeted HPV awareness and preventive health media campaigns. For maximal effect, media campaigns should use the internet, radio, and television to address health care providers, parents, and students. Additional programming can be developed for clinics to use in-house with their clients. Ministries of Education, Finance, and Health all have roles to play to increase national HPV, HPV-related diseases, and HPV vaccination awareness.

Laser micro-dissection and qPCR for identifying specific HPV types responsible for malignancy in penile lesions.

PubMed

Lebelo, Ramokone L; Thys, Sofie; Benoy, Ina; Depuydt, Christophe E; Bogers, John-Paul; Bida, Meshack N; Mphahlele, M Jeffrey

2015-10-01

The aim of the study was to identify specific human papillomavirus (HPV) type responsible for malignancy in penile tissue samples using laser micro-dissection and TaqMan quantitative real-time PCR (qPCR). The study was based on two pre-malignant and seven malignant penile tissue samples and laser micro-dissection was performed on all. Genotyping was performed on whole tissue sections and laser micro-dissection samples using qPCR. Two whole tissue section samples were HPV negative while seven were HPV positive. In four samples that were single HPV infections with whole tissue section PCR, identical HPV types were confirmed with laser micro-dissection PCR. Clearly confirming that the single HPV type detected is responsible for malignancy. In two samples that had multiple HPV infections with whole tissue section PCR, only one HPV type with the highest viral load was detected with laser micro-dissection PCR, suggesting that the HPV type with the highest viral load is most likely the cause of that particular lesion. HPV 11 and/or HPV 16 were the only types detected with laser micro-dissection PCR in these cases, compared to multiple HPV types (HPV 11, HPV 16, HPV 18, HPV 31, HPV 33, HPV 35, and HPV 39) initially detected with whole tissue section PCR. HPV 11 was associated with verrucous lesions while HPV 16 was associated with squamous cell carcinoma and PIN 3 lesions. This study confirms that laser micro-dissection and qPCR are essential tools in identifying the HPV types responsible for malignancy in penile lesions, particularly in samples with multiple infections. © 2015 Wiley Periodicals, Inc.

The E6 and E7 genes of human papillomavirus type 6 have weak immortalizing activity in human epithelial cells.

PubMed Central

Halbert, C L; Demers, G W; Galloway, D A

1992-01-01

Previous studies have shown that the E7 gene of human papillomavirus (HPV) type 16 or 18 alone was sufficient for immortalization of human foreskin epithelial cells (HFE) and that the efficiency was increased in cooperation with the respective E6 gene, whereas the HPV6 E6 or E7 gene was not active in HFE. To detect weak immortalizing activities of the HPV6 genes, cells were infected with recombinant retroviruses containing HPV genes, alone and in homologous and heterologous combinations. The HPV6 genes, alone or together (HPV6 E6 plus HPV6 E7), were not able to immortalize cells. However the HPV6 E6 gene, in concert with HPV16 E7, increased the frequency of immortalization threefold over that obtained with HPV16 E7 alone. Interestingly, 6 of 20 clones containing the HPV16 E6 gene and the HPV6 E7 gene were immortalized, whereas neither gene alone was sufficient. Thus, the HPV6 E6 and E7 genes have weak immortalizing activities which can be detected in cooperation with the more active transforming genes of HPV16. Acute expression of the HPV6 and HPV16 E6 and E7 genes revealed that only HPV16 E7 was able to stimulate the proliferation of cells in organotypic culture, resulting in increased expression of the proliferative cell nuclear antigen and the formation of a disorganized epithelial layer. Additionally, combinations of genes that immortalized HFE cells (HPV16 E6 plus HPV16 E7, HPV16 E6 plus HPV6 E7, and HPV6 E6 plus HPV16 E7) also stimulated proliferation. Images PMID:1312623

Isotropic-resolution linear-array-based photoacoustic computed tomography through inverse Radon transform

NASA Astrophysics Data System (ADS)

Li, Guo; Xia, Jun; Li, Lei; Wang, Lidai; Wang, Lihong V.

2015-03-01

Linear transducer arrays are readily available for ultrasonic detection in photoacoustic computed tomography. They offer low cost, hand-held convenience, and conventional ultrasonic imaging. However, the elevational resolution of linear transducer arrays, which is usually determined by the weak focus of the cylindrical acoustic lens, is about one order of magnitude worse than the in-plane axial and lateral spatial resolutions. Therefore, conventional linear scanning along the elevational direction cannot provide high-quality three-dimensional photoacoustic images due to the anisotropic spatial resolutions. Here we propose an innovative method to achieve isotropic resolutions for three-dimensional photoacoustic images through combined linear and rotational scanning. In each scan step, we first elevationally scan the linear transducer array, and then rotate the linear transducer array along its center in small steps, and scan again until 180 degrees have been covered. To reconstruct isotropic three-dimensional images from the multiple-directional scanning dataset, we use the standard inverse Radon transform originating from X-ray CT. We acquired a three-dimensional microsphere phantom image through the inverse Radon transform method and compared it with a single-elevational-scan three-dimensional image. The comparison shows that our method improves the elevational resolution by up to one order of magnitude, approaching the in-plane lateral-direction resolution. In vivo rat images were also acquired.

Moving-Article X-Ray Imaging System and Method for 3-D Image Generation

NASA Technical Reports Server (NTRS)

Fernandez, Kenneth R. (Inventor)

2012-01-01

An x-ray imaging system and method for a moving article are provided for an article moved along a linear direction of travel while the article is exposed to non-overlapping x-ray beams. A plurality of parallel linear sensor arrays are disposed in the x-ray beams after they pass through the article. More specifically, a first half of the plurality are disposed in a first of the x-ray beams while a second half of the plurality are disposed in a second of the x-ray beams. Each of the parallel linear sensor arrays is oriented perpendicular to the linear direction of travel. Each of the parallel linear sensor arrays in the first half is matched to a corresponding one of the parallel linear sensor arrays in the second half in terms of an angular position in the first of the x-ray beams and the second of the x-ray beams, respectively.

Attitudes towards Human Papilloma Virus Vaccination in the Latin American Andean Region

PubMed Central

2017-01-01

This commentary explores the distribution of human papilloma virus (HPV) and HPV-related diseases, and factors affecting attitudes towards HPV, HPV-related diseases, and HPV vaccination in the Latin American Andean region. Lack of knowledge of HPV, known negative attitudes or incorrect assumptions about HPV, HPV-related diseases, and HPV vaccination provide a basis upon which to develop targeted HPV awareness and preventive health media campaigns. For maximal effect, media campaigns should use the internet, radio, and television to address health care providers, parents, and students. Additional programming can be developed for clinics to use in-house with their clients. Ministries of Education, Finance, and Health all have roles to play to increase national HPV, HPV-related diseases, and HPV vaccination awareness. PMID:28885601

Micro-Machined High-Frequency (80 MHz) PZT Thick Film Linear Arrays

PubMed Central

Zhou, Qifa; Wu, Dawei; Liu, Changgeng; Zhu, Benpeng; Djuth, Frank; Shung, K. Kirk

2010-01-01

This paper presents the development of a micro-machined high-frequency linear array using PZT piezoelectric thick films. The linear array has 32 elements with an element width of 24 μm and an element length of 4 mm. Array elements were fabricated by deep reactive ion etching of PZT thick films, which were prepared from spin-coating of PZT solgel composite. Detailed fabrication processes, especially PZT thick film etching conditions and a novel transferring-and-etching method, are presented and discussed. Array designs were evaluated by simulation. Experimental measurements show that the array had a center frequency of 80 MHz and a fractional bandwidth (−6 dB) of 60%. An insertion loss of −41 dB and adjacent element crosstalk of −21 dB were found at the center frequency. PMID:20889407

Seroconversion Following Anal and Genital HPV Infection in Men: The HIM Study.

PubMed

Giuliano, Anna R; Viscidi, Raphael; Torres, B Nelson; Ingles, Donna J; Sudenga, Staci L; Villa, Luisa L; Baggio, Maria Luiza; Abrahamsen, Martha; Quiterio, Manuel; Salmeron, Jorge; Lazcano-Ponce, Eduardo

2015-12-01

Protection from naturally acquired human papillomavirus (HPV) antibodies may influence HPV infection across the lifespan. This study describes seroconversion rates following genital, anal, and oral HPV 6/11/16/18 infections in men and examines differences by HPV type and anatomic site. Men with HPV 6/11/16/18 infections who were seronegative for those genotypes at the time of DNA detection were selected from the HPV Infection in Men (HIM) Study. Sera specimens collected ≤36 months after detection were analyzed for HPV 6/11/16/18 antibodies using a virus-like particle-based ELISA. Time to seroconversion was separately assessed for each anatomic site, stratified by HPV type. Seroconversion to ≥1 HPV type (6/11/16/18) in this sub-cohort (N=384) varied by anatomic site, with 6.3, 18.9, and 0.0% seroconverting following anal, genital, and oral HPV infection, respectively. Regardless of anatomic site, seroconversion was highest for HPV 6 (19.3%). Overall, seroconversion was highest following anal HPV 6 infection (69.2%). HPV persistence was the only factor found to influence seroconversion. Low seroconversion rates following HPV infection leave men susceptible to recurrent infections that can progress to HPV-related cancers. This emphasizes the need for HPV vaccination in men to ensure immune protection against new HPV infections and subsequent disease.

Reliability of Central Adiposity Assessments Using B-Mode Ultrasound: A Comparison of Linear and Curved Array Transducers.

PubMed

Stoner, Lee; Geoffron, Morgane; Cornwall, Jon; Chinn, Victoria; Gram, Martin; Credeur, Daniel; Fryer, Simon

2016-12-01

Recently, it was reported that intra-abdominal thickness (IAT) assessments using ultrasound are most reliable if measured from the linea alba to the anterior vertebral column. These 2 anatomical sites can be simultaneously visualized using a linear array transducer. Linear array transducers have different operational characteristics when compared with conventional curved array transducers and are more reliable for some ultrasound-derived measures such as abdominal subcutaneous fat thickness. However, it is unknown whether linear array transducers facilitate more reliable IAT measurements than curved array transducers. The purpose of the current study was to (1) compare the reliability of linear and curved array transducer assessments of IAT and maximal abdominal ratio (MAR) and (2) use the findings to update central adiposity measurement guidelines. Fifteen healthy adults (mean [SD], 27 [10] years; 60% female) with a range of somatotypes (body mass index: mean [SD], 24 [4]; range, 19-33 kg/m; waist circumference: mean [SD], 75 [11]; range, 61-96 cm) were tested on 3 mornings under standardized conditions. Intra-abdominal thickness was assessed 2 cm above the umbilicus (transverse plane), measuring from linea alba to the anterior vertebral column. Maximal abdominal ratio was defined as the ratio of IAT to abdominal subcutaneous fat thickness. The IAT range was 25 to 87 mm, and the MAR range was 0.15 to 0.77. Between-day intraclass correlation coefficient values for IAT measurements made were comparable (0.96-0.97) for both transducers, as were MAR values (0.95). In conclusion, while both transducers provided equally reliable measurement of IAT, the use of a single linear array transducer simplifies the assessment of central adiposity.

Analysis of HPV distribution in patients with cervical precancerous lesions in Western China.

PubMed

Li, Kemin; Yin, Rutie; Li, Qingli; Wang, Danqing

2017-07-01

Cervical human papillomavirus (HPV) infection is a dangerous disease, whose subtypes exhibit different distribution patterns in particular countries, regions, and races. In this study, the HPV distribution in patients with cervical precancerous lesions in Western China was investigated to assess a probability for prevention of cervical cancer and the clinical application of an HPV vaccine in China. The retrospective study of patients with different HPV subtypes and cervical precancerous lesions, who have undergone loop eelectrosurgical excision procedure, cold knife conization, or a total hysterectomy in our hospital from January 2016 to August 2016, was performed. All patients were tested for 27 HPV subtypes via the liquid suspension chip technology (Luminex 200). A total of 3393 cases of cervical intraepithelial neoplasia (CIN) were investigated, including 1098 cases of CIN I, 762 cases of CIN II, and 1533 cases of CIN III. The overall HPV infection rate was 82.58%. The high-risk HPV infection rate was 76.61%, and the low-risk rate was 9.88%. The most common 5 subtypes were HPV16, HPV52, HPV58, HPV33, and HPV18. The patients were grouped into 6 age groups: ≤20, 21 to 30, 31 to 40, 41 to 50, 50 to 64, and ≥65. The HPV subtypes' distribution varied across different age groups. In patients with cervical precancerous lesions in Western China, the top 5 HPV subtypes with the highest infection rates were HPV16, HPV52, HPV58, HPV33, and HPV18. The rate of cervical precancerous lesions unrelated to HPV was 17.42%. Thus, HPV screening with no cytology may leave unobserved about 20% of cervical precancerous lesions, which is worth of significant clinical attention.

Transmission of high-risk human papillomavirus (HPV) between parents and infant: a prospective study of HPV in families in Finland.

PubMed

Rintala, Marjut A M; Grénman, Seija E; Puranen, Mirja H; Isolauri, Erika; Ekblad, Ulla; Kero, Pentti O; Syrjänen, Stina M

2005-01-01

The Finnish HPV Family Study is a prospective cohort study assessing the dynamics of human papillomavirus (HPV) transmission between parents and infant. Serial genital and oral scrapings from 76 families, including mother, father, and infant, and semen samples were collected over 2 years of follow-up, analyzed by nested PCR, and confirmed by hybridization with 12 high-risk (HR) HPV types. The most common HPV profile was HR HPV in all family members (29%), followed by HPV-positive mother-infant pairs (26%). HPV-positive father-infant pairs were less frequent (11%), and in six (8%) families, only the infant was HR HPV positive. The prevalence of genital HR HPV in the parents ranged from 13 to 25%, and that of oral HPV ranged from 8 to 34%. In the infants, HPV DNA was detected in 15% of the genital and 10% of the oral samples at birth, reaching peaks of 18 and 21%, respectively, at 6 months, and declining to 10% at 24 months. Persistent HPV in the mother was a risk factor for oral HPV in the infant (odds ratio [OR], 5.69; 95% confidence interval [95% CI], 1.5 to 21.3), while oral HPV in the mother at 6 months was a risk factor for genital HR HPV (OR, 6.38; 95% CI, 1.15 to 35.32). No such independent risk could be attributed to subclinical HPV in the father. Persistent maternal cervical HPV and subclinical oral HPV affect the risk of infant HPV. The age of 6 months is a critical point for the infant to acquire or be free of HR HPV DNA.

Comparison of the immunogenicity of Cervarix® and Gardasil® human papillomavirus vaccines for oncogenic non-vaccine serotypes HPV-31, HPV-33, and HPV-45 in HIV-infected adults.

PubMed

Toft, Lars; Tolstrup, Martin; Müller, Martin; Sehr, Peter; Bonde, Jesper; Storgaard, Merete; Østergaard, Lars; Søgaard, Ole S

2014-01-01

Individuals infected with human immunodeficiency virus (HIV) have excess risk of developing human papillomavirus (HPV)-related disease. A substantial fraction of HPV-associated cancers is caused by HPV serotypes not included in the currently available vaccines. Among healthy women, both Cervarix(®) (HPV-16/18, GlaxoSmithKline Biologicals, GSK) and Gardasil(®) (HPV-6/11/16/18, Merck) have demonstrated partial cross-protection against certain oncogenic non-vaccine HPV-types. Currently, there are no available data on vaccine-induced cross-protection in men and little is known about cross-reactive immunity after HPV-vaccination of HIV-infected individuals. In an investigator-initiated trial, we randomized 91 HIV-positive men and women to receive vaccination with Cervarix(®) or Gardasil(®). The HPV-DNA status of the participants was determined with pcr before and after immunization. Cross-reactive antibody responses against HPV-31, HPV-33, and HPV-45 were evaluated for up to 12 months using a pseudovirion-based neutralization assay (PBNA). Geometric mean antibody titers (GMTs) were compared among vaccine groups and genders at 7 and 12 months.: Both vaccines induced anti-HPV-31, -33, and -45 neutralizing antibodies in participants who were seronegative and HPV-DNA negative for those types at study entry. Geometric mean antibody titers were comparable between vaccine groups. Interestingly, anti-HPV-31 and -33 antibody titers were higher among women compared with men at 7 and 12 months.: In conclusion, both licensed HPV-vaccines induced cross-neutralizing antibodies against frequent oncogenic non-vaccine serotypes HPV-31, HPV-33, and HPV-45 in HIV-infected adults, and women had greater serological responses against HPV-31 and -33 compared with men.

Morphological characteristics of conjunctival squamous papillomas in relation to human papillomavirus infection.

PubMed

Mlakar, Jernej; Kocjan, Boštjan J; Hošnjak, Lea; Pižem, Jože; Beltram, Matej; Gale, Nina; Drnovšek-Olup, Brigita; Poljak, Mario

2015-03-01

To determine the prevalence of a broad spectrum of human papillomavirus (HPV) types in conjunctival papillomas and a possible difference in clinical and histopathological presentation of HPV-positive and HPV-negative papillomas. Formalin-fixed, paraffin-embedded papilloma tissue specimens obtained from 25 patients were analysed using six different PCR-based methods targeting 87 HPV types from four different papillomavirus (PV) genera: α-PV, β-PV, γ-PV and µ-PV, and in situ hybridisation for HPV-6/HPV-11. Slides were reviewed for pedunculated or sessile growth, the presence of goblet cells, keratinising or non-keratinising epithelium, elastosis, atypia and koilocytes. α-PV types HPV-6 and HPV-11 were detected in 19/25 (76%) conjunctival papilloma tissue specimens, 9 (47%) of which were also HPV-6/HPV-11 positive with in situ hybridisation. Six different β-PV types-HPV-9, HPV-12, HPV-20, HPV-21, HPV-22, HPV-24-were additionally detected in four cases, all of which were also HPV-6/HPV-11 positive. No γ-PVs or µ-PVs were found in any of the tested tissues samples. Extralimbal location (p=0.021), presence of goblet cells (p=0.005), non-keratinising squamous epithelium (p=0.005), and absence of elastosis (p=0.005) were associated with the presence of HPV-6/HPV-11. We demonstrated that certain clinical and histological features are more frequently associated with HPV infection and that HPV genera other than α-PV are most probably not significant factors in conjunctival papilloma occurrence. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Quantitation of Human Papillomavirus DNA in Plasma of Oropharyngeal Carcinoma Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cao Hongbin; Banh, Alice; Kwok, Shirley

Purpose: To determine whether human papillomavirus (HPV) DNA can be detected in the plasma of patients with HPV-positive oropharyngeal carcinoma (OPC) and to monitor its temporal change during radiotherapy. Methods and Materials: We used polymerase chain reaction to detect HPV DNA in the culture media of HPV-positive SCC90 and VU147T cells and the plasma of SCC90 and HeLa tumor-bearing mice, non-tumor-bearing controls, and those with HPV-negative tumors. We used real-time quantitative polymerase chain reaction to quantify the plasma HPV DNA in 40 HPV-positive OPC, 24 HPV-negative head-and-neck cancer patients and 10 non-cancer volunteers. The tumor HPV status was confirmed bymore » p16{sup INK4a} staining and HPV16/18 polymerase chain reaction or HPV in situ hybridization. A total of 14 patients had serial plasma samples for HPV DNA quantification during radiotherapy. Results: HPV DNA was detectable in the plasma samples of SCC90- and HeLa-bearing mice but not in the controls. It was detected in 65% of the pretreatment plasma samples from HPV-positive OPC patients using E6/7 quantitative polymerase chain reaction. None of the HPV-negative head-and-neck cancer patients or non-cancer controls had detectable HPV DNA. The pretreatment plasma HPV DNA copy number correlated significantly with the nodal metabolic tumor volume (assessed using {sup 18}F-deoxyglucose positron emission tomography). The serial measurements in 14 patients showed a rapid decline in HPV DNA that had become undetectable at radiotherapy completion. In 3 patients, the HPV DNA level had increased to a discernable level at metastasis. Conclusions: Xenograft studies indicated that plasma HPV DNA is released from HPV-positive tumors. Circulating HPV DNA was detectable in most HPV-positive OPC patients. Thus, plasma HPV DNA might be a valuable tool for identifying relapse.« less

Double demonstration of oncogenic high risk human papilloma virus DNA and HPV-E7 protein in oral cancers.

PubMed

Pannone, G; Santoro, A; Carinci, F; Bufo, P; Papagerakis, S M; Rubini, C; Campisi, G; Giovannelli, L; Contaldo, M; Serpico, R; Mazzotta, M; Lo Muzio, L

2011-01-01

Oncogenic HPVs are necessarily involved in cervical cancer but their role in oral carcinogenesis is debated. To detect HPV in oral cancer, 38 cases of formalin fixed-paraffin embedded OSCC were studied by both DNA genotyping (MY09/11 L1 consensus primers in combination with GP5-GP6 primer pair followed by sequencing) and immunohistochemistry (monoclonal Abs against capsid protein and HPV-E7 protein, K1H8 DAKO and clone 8C9 INVITROGEN, respectively). HPV-16 tonsil cancer was used as positive control. The overall prevalence of HPV infection in OSCCs was 10.5%. Amplification of DNA samples showed single HPV DNA infection in 3 cases (HPV16; HPV53; HPV70) and double infection in one case of cheek cancer (HPV31/HPV44). The overall HR-HPV prevalence was 7.5%. E-7 antigen was immunohistochemically detected in all HPV-positive cases. HPV+ OSCC cases showed an overall better outcome than HPV negative oral cancers, as evaluated by Kaplan-Meier curves. HPVs exert their oncogenic role after DNA integration, gene expression of E5, E6 and E7 loci and p53/pRb host proteins suppression. This study showed that HPV-E7 protein inactivating pRb is expressed in oral cancer cells infected by oncogenic HPV other than classical HR-HPV-16/18. Interestingly HPV-70, considered a low risk virus with no definite collocation in oncogenic type category, gives rise to the expression of HPV-E7 protein and inactivate pRb in oral cancer. HPV-70, as proved in current literature, is able to inactivates also p53 protein, promoting cell immortalization. HPV-53, classified as a possible high risk virus, expresses E7 protein in OSCC, contributing to oral carcinogenesis. We have identified among OSCCs, a subgroup characterized by HPV infection (10.5%). Finally, we have proved the oncogenic potential of some HPV virus types, not well known in literature.

Comparison of the immunogenicity of the human papillomavirus (HPV)-16/18 vaccine and the HPV-6/11/16/18 vaccine for oncogenic non-vaccine types HPV-31 and HPV-45 in healthy women aged 18-45 years.

PubMed

Einstein, Mark H; Baron, Mira; Levin, Myron J; Chatterjee, Archana; Fox, Bradley; Scholar, Sofia; Rosen, Jeffrey; Chakhtoura, Nahida; Lebacq, Marie; van der Most, Robbert; Moris, Philippe; Giannini, Sandra L; Schuind, Anne; Datta, Sanjoy K; Descamps, Dominique

2011-12-01

Protection against oncogenic non-vaccine types (cross-protection) offered by human papillomavirus (HPV) vaccines may provide a significant medical benefit. Available clinical efficacy data suggest the two licensed vaccines (HPV-16/18 vaccine, GlaxoSmithKline Biologicals (GSK), and HPV-6/11/16/18 vaccine, Merck & Co., Inc.) differ in terms of protection against oncogenic non-vaccine HPV types -31/45. The immune responses induced by the two vaccines against these two non-vaccine HPV types (cross-reactivity) was compared in an observer-blind study up to Month 24 (18 mo post-vaccination), in women HPV DNA-negative and seronegative prior to vaccination for the HPV type analyzed (HPV-010 [NCT00423046]). Geometric mean antibody titers (GMTs) measured by pseudovirion-based neutralization assay (PBNA) and enzyme-linked immunosorbent assay (ELISA) were similar between vaccines for HPV-31/45. Seropositivity rates for HPV-31 were also similar between vaccines; however, there was a trend for higher seropositivity with the HPV-16/18 vaccine (13.0-16.7%) versus the HPV-6/11/16/18 vaccine (0.0-5.0%) for HPV-45 with PBNA, but not ELISA. HPV-31/45 cross-reactive memory B-cell responses were comparable between vaccines. Circulating antigen-specific CD4+ T-cell frequencies were higher for the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (HPV-31 [geometric mean ratio [GMR] =2.0; p=0.0002] and HPV-45 [GMR=2.6; p=0.0092]), as were the proportion of T-cell responders (HPV-31, p=0.0009; HPV-45, p=0.0793). In conclusion, immune response to oncogenic non-vaccine HPV types -31/45 was generally similar for both vaccines with the exception of T-cell response which was higher with the HPV-16/18 vaccine. Considering the differences in cross-protective efficacy between the two vaccines, the results might provide insights into the underlying mechanism(s) of protection.

Cytology and high risk HPV testing in cervical cancer screening program: Outcome of 3-year follow-up in an academic institute.

PubMed

Yang, Jack; Nolte, Fredrick S; Chajewski, Olga S; Lindsey, Kathryn G; Houser, Patricia M; Pellicier, Jalidsa; Wang, Qun; Ehsani, Laleh

2018-01-01

Combination of cervical cytology and high-risk human papillomavirus (HR-HPV) testing, co-testing, has been increasingly used in screening cervical cancers. The present study summarized the outcome of co-testing by reviewing 3-year clinical and pathological follow-up information. Patients were retrospectively identified via computerized search and were grouped based on the cytologic diagnosis and HR-HPV status as negative for intraepithelial lesion or malignancy (NILM)/HPV-, NILM/HPV+, atypical squamous cells of undetermined significance (ASC-US)/HPV-, ASC-US/HPV+, low grade squamous intraepithelial lesion (LSIL)/HPV-, LSIL/HPV+, atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion (ASC-H)/HPV-, ASC-H/HPV+, high grade squamous intraepithelial lesion (HSIL)/HPV-, and HSIL/HPV+. The patients' pertinent past medical history and follow-up information were analyzed. During 3-year follow-up period, histologically proven HSIL was found in 5 of 1565 (0.3%) patients with NILM/HPV-, 7 of 141 (5.0%) with NILM/HPV+, 2 of 502 (0.4%) with ASC-US/HPV-, 30 of 274 (10.9%) with ASC-US/HPV+, 1 of 81 (1.2%) with LSIL/HPV-, 28 of 159 (17.6%) with LSIL/HPV+, 3 of 18 (16.7%) with ASC-H/HPV-, 34 of 69 (49.3%) with ASC-H/HPV+, 7 of 7 (100%) with HSIL/HPV-, and 35 of 56 (62.5%) HSIL/HPV+. In reviewing 12 HSIL cases that were originally diagnosed as NILM, 7 remained as NILM, and the other 5 were reclassified as 1 HSIL, 1 ASC-H, and 3 ASC-US, respectively. In 18 HSIL cases with negative HR-HPV, 12 patients had a prior history of positive HR-HPV testing and/or positive p16 IHC stain in the follow-up cervical biopsy. HR-HPV testing plays an important role in cervical cancer screening by identifying HSIL in patients with ASC-US, LSIL, and NILM. Co-testing is an optimal method to identifying the patients with higher risk for developing cervical abnormalities. © 2017 Wiley Periodicals, Inc.

Comparison of the immunogenicity of the human papillomavirus (HPV)-16/18 vaccine and the HPV-6/11/16/18 vaccine for oncogenic non-vaccine types HPV-31 and HPV-45 in healthy women aged 18–45 years

PubMed Central

Baron, Mira; Levin, Myron J; Chatterjee, Archana; Fox, Bradley; Scholar, Sofia; Rosen, Jeffrey; Chakhtoura, Nahida; Lebacq, Marie; van der Most, Robbert; Moris, Philippe; Giannini, Sandra L; Schuind, Anne; Datta, Sanjoy K; Descamps, Dominique

2011-01-01

Protection against oncogenic non-vaccine types (cross-protection) offered by human papillomavirus (HPV) vaccines may provide a significant medical benefit. Available clinical efficacy data suggest the two licensed vaccines [HPV-16/18 vaccine, GlaxoSmithKline Biologicals (GSK), and HPV-6/11/16/18 vaccine, Merck and Co., Inc.,] differ in terms of protection against oncogenic non-vaccine HPV types -31/45. The immune responses induced by the two vaccines against these two non-vaccine HPV types (cross-reactivity) was compared in an observer-blind study up to Month 24 (18 mo postvaccination), in women HPV DNA-negative and seronegative prior to vaccination for the HPV type analyzed [HPV-010 (NCT00423046)]. Geometric mean antibody titers (GMTs) measured by pseudovirion-based neutralization assay (PBNA) and enzyme-linked immunosorbent assay (ELISA ) were similar between vaccines for HPV-31/45. Seropositivity rates for HPV-31 were also similar between vaccines; however, there was a trend for higher seropositivity with the HPV-16/18 vaccine (13.0–16.7%) vs. the HPV-6/11/16/18 vaccine (0.0–5.0%) for HPV-45 with PBNA, but not ELISA . HPV-31/45 cross-reactive memory B-cell responses were comparable between vaccines. Circulating antigen-specific CD4+ T-cell frequencies were higher for the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine {HPV-31 [geometric mean ratio (GMR) = 2.0; p = 0.0002] and HPV-45 [GMR = 2.6; p = 0.0092]}, as were the proportion of T-cell responders (HPV-31, p = 0.0009; HPV-45, p = 0.0793). In conclusion, immune response to oncogenic non-vaccine HPV types -31/45 was generally similar for both vaccines with the exception of T-cell response which was higher with the HPV-16/18 vaccine. Considering the differences in cross-protective efficacy between the two vaccines, the results might provide insights into the underlying mechanism(s) of protection. PMID:22048172

Evaluation of HPV type-replacement in unvaccinated and vaccinated adolescent females-Post-hoc analysis of a community-randomized clinical trial (II).

PubMed

Gray, Penelope; Palmroth, Johanna; Luostarinen, Tapio; Apter, Dan; Dubin, Gary; Garnett, Geoff; Eriksson, Tiina; Natunen, Kari; Merikukka, Marko; Pimenoff, Ville; Söderlund-Strand, Anna; Vänskä, Simopekka; Paavonen, Jorma; Pukkala, Eero; Dillner, Joakim; Lehtinen, Matti

2018-06-15

Efficacy of human papillomavirus (HPV) vaccines promises to control HPV infections. However, HPV vaccination programs may lay bare an ecological niche for non-vaccine HPV types. We evaluated type-replacement by HPV type and vaccination strategy in a community-randomized trial executed in HPV vaccination naïve population. Thirty-three communities were randomized to gender-neutral vaccination with AS04-adjuvanted HPV16/18 vaccine (Arm A), HPV vaccination of girls and hepatitis B-virus (HBV) vaccination of boys (Arm B) and gender-neutral HBV vaccination (Arm C). Resident 1992-95 born boys (40,852) and girls (39,420) were invited. 11,662 boys and 20,513 girls were vaccinated with 20-30% and 45-48% coverage, respectively. HPV typing of 11,396 cervicovaginal samples was performed by high throughput PCR. Prevalence ratios (PR) between arms and ranked order of HPV types and odds ratio (OR) for having multiple HPV types in HPV16 or 18/45 positive individuals were calculated. The ranked order of HPV types did not significantly differ between arms or birth cohorts. For the non-HPV vaccinated 1992-1993 birth cohorts increased PR, between the gender-neutral intervention versus control arms for HPV39 (PR A 1.84, 95% CI 1.12-3.02) and HPV51 (PR A 1.56, 95% CI 1.11-2.19) were observed. In the gender-neutral arm, increased clustering between HPV39 and the vaccine-covered HPV types 16 or 18/45 (OR A16  = 5.1, OR A18/45  = 11.4) was observed in the non-HPV vaccinated 1994-1995 birth cohorts. Comparable clustering was seen between HPV51 and HPV16 or HPV18/45 (OR B16  = 4.7, OR B18/45  = 4.3), in the girls-only arm. In conclusion, definitively consistent postvaccination patterns of HPV type-replacement were not observed. Future occurrence of HPV39 and HPV51 warrant investigation. © 2018 UICC.

[Anticipated efficacy of HPV vaccination in prophylaxis against nongenital cancers].

PubMed

Sehnal, B; Vojáčková, N; Driák, D; Kmoníčková, E; Vaňousová, D; Maxová, K; Neumannová, H; Sláma, J

2014-01-01

There is a considerable number of studies on the efficacy HPV (human papillomavirus) vaccination against different cancers but relevant information is scattered in diverse journals. This paper is a review summarizing current knowledge of the potential of HPV vaccination against all HPV related cancers. HPV infection is probably the most frequent sexually transmitted disease. At least 13 HPV genotypes are classified as carcinogenic or probably carcinogenic in respect to cervical cancer. Almost 100% of cervical cancers are linked to HPV infection. HPV 16 and HPV 18 are the most frequently involved genotypes and account together for approximately 70% of cervical cancer in the world. Persistent high risk HPV infection is responsible for a significant proportion of vulvar, vaginal, anal and penile carcinomas. The virus has also been implicated in oncogenesis of head and neck cancers, including oropharyngeal cancers. HPV infection can play an important role in cancerogenesis of lung, esophagus, breast, and colon and rectum. On the contrary, published results indicate that HPV infection is not associated with prostate oncogenesis. Strong predominance of HPV 16 has been reported for all HPV associated cancer sites. Generally, it is estimated that approximately 5.2% of all cancers are associated with oncogenic HPV infection. Currently, there are two vaccines on the market; quadrivalent Silgard® (Gardasil®) and bivalent CervarixTM. Large trials for both vaccines have shown efficacy against HPV related infection and disease. Efficacy has been very high in HPV naive subjects to vaccine related types. While HPV vaccination is currently approved for the prevention of cervical cancer, it also has the potential in the prevention of all HPV associated malignancies. The Czech republic belongs to countries that cover HPV vaccination of girls at the age of 13- 14 years by general health insurance. Overall impact of this vaccination remains to be evaluated. The new issues of the role of HPV in oncogenesis, as well as the potential effect of HPV vaccination against HPV related nongenital cancers are discussed. Approximately 5.2% of all human cancers are associated with oncogenic human papillomavirus infection. HPV vaccination against the most risky HPV oncotypes may cause a significant reduction of these cancers mainly in the HPV naive population.

HPV genotype distribution and anomalous association of HPV33 to cervical neoplastic lesions in San Luis Potosí, Mexico.

PubMed

DelaRosa-Martínez, Raúl; Sánchez-Garza, Mireya; López-Revilla, Rubén

2016-01-01

The association of human papillomavirus (HPV) types to neoplastic lesions increase as a function of their oncogenicity and the duration of the infection since lesion severity progresses from low-grade to high-grade and cancer. In an outbreak, the prevalence of the HPV type involved would increase and the proportion of the associated low-grade lesions would predominate over severe lesions. In this study, the prevalence of HPV types and their association to neoplastic lesions was determined in women subjected to colposcopy in San Luis Potosí, Mexico. DNA from high-risk (HR) and low-risk (LR) HPV types was identified by E6 nested multiplex PCR in cervical scrapes from 700 women with normal cytology, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL) or invasive cervical cancer (CC). Overall HPV-DNA prevalence was 67.7 %, that of HR-HPV was 63.1 %, and that of LR-HPV was 21.3 %. The highest prevalence (78.2 %) occurred in the 15-24 year group, whereas that of single infections was 52 % and that of multiple infections (i.e., by 2-6 HPV types) was 48 %. The most prevalent HR types were HPV33 (33.1 %), HPV16 (16.6 %), HPV18 and HPV51 (6.7 % each). HR-HPV prevalence was 29.6 % in normal cytology, 26.7 % in ASCUS, 63.3 % in LSIL, 68.2 % in HSIL, and 90.5 % in CC. Three prevalence trends for HR-HPV types were found in neoplastic lesions of increasing severity: increasing (LSIL < HSIL < CC) for HPV16, HPV39, HPV18, HPV58, HPV31 and HPV35; asymptotic (LSIL < HSIL ≈ CC) for HPV51 and HPV68; U-shaped (LSIL < HSIL > CC) for HPV33. Two-thirds of the women subjected to colposcopy from 2007 to 2010 in San Luis Potosí have HPV infections which predominate in the 15-24 years group. Around half of the infections are by one viral type and the rest by 2-6 types. HPV33 is the most prevalent type, followed by HPV16. Overall HR-HPV prevalence increases with the severity of neoplastic lesions. HPV33 prevalence is highest in LSIL and its U-shaped trend with progressing neoplastic lesions differs from the growing/asymptotic trends of other HR-HPV types. An ongoing or recent HPV33 outbreak is consistent with its high prevalence and anomalous association to LSIL.

Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine administered according to 2- and 3-dose schedules in girls aged 9–14 years: Results to month 12 from a randomized trial

PubMed Central

Leung, Ting Fan; Liu, Anthony Pak-Yin; Lim, Fong Seng; Thollot, Franck; Oh, Helen May Lin; Lee, Bee Wah; Rombo, Lars; Tan, Ngiap Chuan; Rouzier, Roman; Friel, Damien; De Muynck, Benoit; De Simoni, Stéphanie; Suryakiran, Pemmaraju; Hezareh, Marjan; Folschweiller, Nicolas; Thomas, Florence; Struyf, Frank

2015-01-01

This observer-blind study (clinicaltrials.gov NCT01462357) compared the immunogenicity and safety of 2 doses of the HPV-16/18 AS04-adjuvanted vaccine (HPV-16/18(2D)) vs. 2 or 3 doses of the HPV-6/11/16/18 vaccine (HPV-6/11/16/18(2D) and HPV-6/11/16/18(3D)) in healthy girls aged 9–14 y. Girls were randomized (1:1:1) to receive HPV-16/18(2D) at months (M) 0,6 (N = 359), HPV-6/11/16/18(2D) at M0,6 (N = 358) or HPV-6/11/16/18(3D) at M0,2,6 (N = 358). The primary objective was non-inferiority/superiority of HPV-16/18 antibodies by ELISA for HPV-16/18(2D) vs. HPV-6/11/16/18(2D) at M7 in the according-to-protocol immunogenicity cohort (ATP-I) and total vaccinated cohort, respectively. Secondary objectives included non-inferiority/superiority of HPV-16/18(2D) vs. HPV-6/11/16/18(3D) at M7, non-inferiority/superiority at M12, HPV-16/18 neutralizing antibodies, frequencies of T-cells/B-cells, reactogenicity and safety. Antibody responses at M7 for HPV-16/18(2D) were superior to those for HPV-6/11/16/18(2D) and HPV-6/11/16/18(3D) (lower limit of 95% confidence interval for geometric mean titer ratio (GMR) was >1): HPV-16/18(2D)/HPV-6/11/16/18(2D) GMRs were 1.69 [1.49–1.91] for anti-HPV-16 and 4.52 [3.97–5.13] for anti-HPV-18; HPV-16/18(2D)/HPV-6/11/16/18(3D) GMRs were 1.72 [1.54–1.93] for anti-HPV-16 and 3.22 [2.82–3.68] for anti-HPV-18; p = 0.0001 for all comparisons. Non-inferiority/superiority was also demonstrated at M12. Among initially seronegative girls in the ATP-I, neutralizing antibody titers were at least 1.8-fold higher for HPV-16/18(2D) vs. HPV-6/11/16/18(2D) and HPV-6/11/16/18(3D) at M7 and M12. Frequencies of HPV-16/18-specific T-cells and B-cells were in similar ranges between groups. Reactogenicity and safety were in line with the known profile of each vaccine. In conclusion, superior HPV-16/18 antibody responses were elicited by 2 doses of the HPV-16/18 AS04-adjuvanted vaccine compared with 2 or 3 doses of the HPV-6/11/16/18 vaccine in girls (9–14 years). PMID:26062002

Predictors of Adults' Knowledge and Awareness of HPV, HPV-Associated Cancers, and the HPV Vaccine: Implications for Health Education

ERIC Educational Resources Information Center

McBride, Kimberly R.; Singh, Shipra

2018-01-01

High human papillomavirus (HPV) prevalence and low HPV vaccine uptake are significant public health concerns. Disparities in HPV-associated cancers and HPV vaccine uptake rates suggest the need for additional research examining factors associated with vaccine acceptance. This study assessed HPV awareness and knowledge and identified…

The Sequencing Bead Array (SBA), a Next-Generation Digital Suspension Array

PubMed Central

Akhras, Michael S.; Pettersson, Erik; Diamond, Lisa; Unemo, Magnus; Okamoto, Jennifer; Davis, Ronald W.; Pourmand, Nader

2013-01-01

Here we describe the novel Sequencing Bead Array (SBA), a complete assay for molecular diagnostics and typing applications. SBA is a digital suspension array using Next-Generation Sequencing (NGS), to replace conventional optical readout platforms. The technology allows for reducing the number of instruments required in a laboratory setting, where the same NGS instrument could be employed from whole-genome and targeted sequencing to SBA broad-range biomarker detection and genotyping. As proof-of-concept, a model assay was designed that could distinguish ten Human Papillomavirus (HPV) genotypes associated with cervical cancer progression. SBA was used to genotype 20 cervical tumor samples and, when compared with amplicon pyrosequencing, was able to detect two additional co-infections due to increased sensitivity. We also introduce in-house software Sphix, enabling easy accessibility and interpretation of results. The technology offers a multi-parallel, rapid, robust, and scalable system that is readily adaptable for a multitude of microarray diagnostic and typing applications, e.g. genetic signatures, single nucleotide polymorphisms (SNPs), structural variations, and immunoassays. SBA has the potential to dramatically change the way we perform probe-based applications, and allow for a smooth transition towards the technology offered by genomic sequencing. PMID:24116138

Recommendations for a national agenda to substantially reduce cervical cancer

PubMed Central

Brewer, Noel T.; Saslow, Debbie; Alexander, Kenneth; Chernofsky, Mildred R.; Crosby, Richard; Derting, Libby; Devlin, Leah; Dunton, Charles J.; Engle, Jeffrey; Fernandez, Maria; Fouad, Mona; Huh, Warner; Kinney, Walter; Pierce, Jennifer; Rios, Elena; Rothholz, Mitchel C.; Shlay, Judith C.; Shedd-Steele, Rivienne; Vernon, Sally W.; Walker, Joan; Wynn, Theresa; Zimet, Gregory D.; Casey, Baretta R.

2016-01-01

Purpose Prophylactic human papillomavirus (HPV) vaccines and new HPV screening tests, combined with traditional Pap test screening, provide an unprecedented opportunity to greatly reduce cervical cancer in the USA. Despite these advances, thousands of women continue to be diagnosed with and die of this highly preventable disease each year. This paper describes the initiatives and recommendations of national cervical cancer experts toward preventing and possibly eliminating this disease. Methods In May 2011, Cervical Cancer-Free America, a national initiative, convened a cervical cancer summit in Washington, DC. Over 120 experts from the public and private sector met to develop a national agenda for reducing cervical cancer morbidity and mortality in the USA. Results Summit participants evaluated four broad challenges to reducing cervical cancer: (1) low use of HPV vaccines, (2) low use of cervical cancer screening, (3) screening errors, and (4) lack of continuity of care for women diagnosed with cervical cancer. The summit offered 12 concrete recommendations to guide future national and local efforts toward this goal. Conclusions Cervical cancer incidence and mortality can be greatly reduced by better deploying existing methods and systems. The challenge lies in ensuring that the array of available prevention options are accessible and utilized by all age-appropriate women—particularly minority and underserved women who are disproportionately affected by this disease. The consensus was that cervical cancer can be greatly reduced and that prevention efforts can lead the way towards a dramatic reduction in this preventable disease in our country. PMID:23828553

Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine: follow-up from months 12-24 in a Phase III randomized study of healthy women aged 18-45 years.

PubMed

Einstein, Mark H; Baron, Mira; Levin, Myron J; Chatterjee, Archana; Fox, Bradley; Scholar, Sofia; Rosen, Jeffrey; Chakhtoura, Nahida; Meric, Dorothée; Dessy, Francis J; Datta, Sanjoy K; Descamps, Dominique; Dubin, Gary

2011-12-01

In this observer-blind study (NCT00423046), women (N=1,106), stratified by age (18-26, 27-35, 36-45 y), were randomized (1:1) to receive the HPV-16/18 vaccine (Cervarix®, GlaxoSmithKline Biologicals, Months 0, 1, 6) or the HPV-6/11/16/18 vaccine (Gardasil® Merck & Co., Inc., Months 0, 2, 6). Month 7 results were previously reported; we now report Month 24 results. In the according-to-protocol cohort for immunogenicity (seronegative and DNA-negative at baseline for HPV type analyzed), seropositivity rates of neutralizing antibodies (nAbs) [pseudovirion-based neutralization assay] were, across all age strata, 100% (HPV-16/18 vaccine) and 97.5-100% (HPV-6/11/16/18 vaccine) for HPV-16, and 99.0-100% (HPV-16/18 vaccine) and 72.3-84.4% (HPV-6/11/16/18 vaccine) for HPV-18. Corresponding geometric mean titers (GMTs) were 2.4-5.8-fold higher for HPV-16 and 7.7-9.4-fold higher for HPV-18 with the HPV-16/18 vaccine versus the HPV-6/11/16/18 vaccine; HPV-16 and HPV-18 GMTs were significantly higher with the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (p< 0.0001) in the total vaccinated cohort (received ≥1 vaccine dose, irrespective of baseline sero/DNA-status). Similar results were obtained using enzyme-linked immunosorbent assay (ELISA). Positivity rates and GMTs of antigen-specific IgG antibodies in cervicovaginal secretions (ELISA) were not significantly different between vaccines. At Month 24, CD4⁺ T-cell responses for HPV-16 and HPV-18 were higher with the HPV-16/18 vaccine; memory B-cell response was higher for HPV-18 with the HPV-16/18 vaccine and similar between vaccines for HPV-16. Both vaccines were generally well tolerated. Although an immunological correlate of protection has not been defined, differences in the magnitude of immune response between vaccines may represent determinants of duration of protection.

"Histological characteristics of HPV-associated and -independent squamous cell carcinomas of the vulva: A study of 1,594 cases".

PubMed

Rakislova, Natalia; Clavero, Omar; Alemany, Laia; Saco, Adela; Quirós, Beatriz; Lloveras, Belen; Alejo, Maria; Pawlita, Michael; Quint, Wim; Del Pino, Marta; de Sanjose, Silvia; Ordi, Jaume

2017-12-15

There are at least two different etio-pathogenic pathways for the development of vulvar squamous cell carcinoma (VSCC): one associated with infection by human papillomavirus (HPV) and another independent of HPV. We aimed to describe the histological characteristics of HPV-associated and -independent tumors and to determine the best strategy to identify HPV in VSCC. A single paraffin block was available for review from a series of 1,594 VSCCs. In all cases HPV DNA detection was analyzed using the SPF10PCR/DEIA/LiPA25 system and p16 immunohistochemistry (IHC). A tumor was considered as unquestionably HPV-associated if both HPV DNA and p16 IHC were positive. A tumor was considered indisputably HPV-independent if both HPV DNA and p16 IHC were negative. Two groups of tumors were classified as non-conclusive: (1) HPV DNA+/p16- and (2) HPV DNA-/p16+. WHO typing and a thorough histological evaluation were conducted in all cases. Four hundred and forty-one tumors were HPV DNA+ with 367 cases (23.0%) being HPV DNA+/p16+. The latter tumors were more frequently basaloid or warty (49.8%), but 36.5% were of the keratinizing type; 1,153 tumors were HPV DNA-, with 1,060 cases (66.5%) being HPV DNA-/p16-. These HPV DNA-/p16- tumors were mostly keratinizing (81.2%) but were occasionally basaloid or warty (5.2%). The features of HPV DNA-/p16+ cases (n = 93) were similar to those of the HPV-associated VSCC, and HPV DNA+/p16- (n = 74) cases had a more diverse profile, although they were more similar to HPV-independent tumors. Several histological characteristics were more frequently associated with HPV-related VSCC (koilocytotic-like change, necrosis, moderate to marked pleomorphism, invasive front in nests; p < 0.001), however, none of these characteristics allowed differentiation between HPV-associated and -independent VSCC. In conclusion, histological criteria do not allow differentiation between HPV-associated and -independent VSCC. p16 Alone is a clinically easy strategy to determine HPV status in VSCC. © 2017 UICC.

HPV16/18 genotyping for the triage of HPV positive women in primary cervical cancer screening in Chile.

PubMed

Lagos, Marcela; Van De Wyngard, Vanessa; Poggi, Helena; Cook, Paz; Viviani, Paola; Barriga, María Isabel; Pruyas, Martha; Ferreccio, Catterina

2015-01-01

We previously conducted a population-based screening trial of high-risk human papillomavirus (hrHPV) testing and conventional cytology, demonstrating higher sensitivity (92.7 % vs 22.1 % for CIN2+) but lower positive predictive value (10.5 % vs 23.9 %) of hrHPV testing. Here we report the performance of HPV16/18 genotyping to triage the hrHPV positive participants. Women aged 25 years and older received hrHPV (Hybrid Capture 2) and Papanicolaou testing; positives by either test underwent colposcopy and directed biopsy, as did a sample of double-negatives. hrHPV positive women were reflex-tested with HPV16/18 genotyping (Digene HPV Genotyping PS Test). Among the 8,265 participants, 10.7 % were hrHPV positive, 1.7 % had ASCUS+ cytology, 1.2 % had CIN2+; 776 (88 %) hrHPV positive women had complete results, of whom 38.8 % were positive for HPV16 (24.0 %), HPV18 (9.7 %) or both (5.1 %). CIN2+ prevalence in HPV16/18 positive women (16.3 %, 95 % CI 12.3-20.9) was twice that of HPV16/18 negative women (8.0 %, 95 % CI 5.7-10.8). HPV16/18 genotyping identified 40.5 % of CIN2, 66.7 % of CIN3 and 75.0 % of cancers. Compared to hrHPV screening alone, HPV16/18 triage significantly reduced the referral rate (10.7 % vs 3.7 %) and the number of colposcopies required to detect one CIN2+ (9 vs 6). When HPV16/18 negative women with baseline ASCUS+ cytology were also colposcopied, an additional 14 % of CIN2+ was identified; referral increased slightly to 4.2 %. HPV16/18 triage effectively stratified hrHPV positive women by their risk of high-grade lesions. HPV16/18 positive women must be referred immediately; referral could be deferred in HPV16/18 negative women given the slower progression of non-HPV16/18 lesions, however, they will require active follow-up.

Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine

PubMed Central

Baron, Mira; Levin, Myron J; Chatterjee, Archana; Fox, Bradley; Scholar, Sofia; Rosen, Jeffrey; Chakhtoura, Nahida; Meric, Dorothée; Dessy, Francis J; Datta, Sanjoy K; Descamps, Dominique; Dubin, Gary

2011-01-01

In this observer-blind study (NCT00423046), women (N = 1,106), stratified by age (18–26, 27–35, 36–45 y), were randomized (1:1) to receive the HPV-16/18 vaccine (Cervarix®, GlaxoSmithKline Biologicals, Months 0, 1, 6) or the HPV-6/11/16/18 vaccine (Gardasil® Merck and Co., Inc., Months 0, 2, 6). Month 7 results were previously reported; we now report Month 24 results. In the according-to-protocol cohort for immunogenicity (seronegative and DNA-negative at baseline for HPV type analyzed), seropositivity rates of neutralizing antibodies (nAbs) [pseudovirion-based neutralization assay] were, across all age strata, 100% (HPV-16/18 vaccine) and 97.5–100% (HPV-6/11/16/18 vaccine) for HPV-16, and 99.0–100% (HPV-16/18 vaccine) and 72.3–84.4% (HPV-6/11/16/18 vaccine) for HPV-18. Corresponding geometric mean titers (GMTs) were 2.4–5.8-fold higher for HPV-16 and 7.7–9.4-fold higher for HPV-18 with the HPV-16/18 vaccine vs. the HPV-6/11/16/18 vaccine; HPV-16 and HPV-18 GMTs were significantly higher with the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (p < 0.0001) in the total vaccinated cohort (received ≥1 vaccine dose, irrespective of baseline sero/DNA-status). Similar results were obtained using enzyme-linked immunosorbent assay (ELISA ). Positivity rates and GMTs of antigen-specific IgG antibodies in cervicovaginal secretions (ELISA) were not significantly different between vaccines. At Month 24, CD4+ T-cell responses for HPV-16 and HPV-18 were higher with the HPV-16/18 vaccine; memory B-cell response was higher for HPV-18 with the HPV-16/18 vaccine and similar between vaccines for HPV-16. Both vaccines were generally well tolerated. Although an immunological correlate of protection has not been defined, differences in the magnitude of immune response between vaccines may represent determinants of duration of protection. PMID:22048173

Human Papillomavirus Type 6 and 11 Genetic Variants Found in 71 Oral and Anogenital Epithelial Samples from Australia

PubMed Central

Danielewski, Jennifer A.; Garland, Suzanne M.; McCloskey, Jenny; Hillman, Richard J.; Tabrizi, Sepehr N.

2013-01-01

Genetic variation of 49 human papillomavirus (HPV) 6 and 22 HPV11 isolates from recurrent respiratory papillomatosis (RRP) (n = 17), genital warts (n = 43), anal cancer (n = 6) and cervical neoplasia cells (n = 5), was determined by sequencing the long control region (LCR) and the E6 and E7 genes. Comparative analysis of genetic variability was examined to determine whether different disease states resulting from HPV6 or HPV11 infection cluster into distinct variant groups. Sequence variation analysis of HPV6 revealed that isolates cluster into variants within previously described HPV6 lineages, with the majority (65%) clustering to HPV6 sublineage B1 across the three genomic regions examined. Overall 72 HPV6 and 25 HPV11 single nucleotide variations, insertions and deletions were observed within samples examined. In addition, missense alterations were observed in the E6/E7 genes for 6 HPV6 and 5 HPV11 variants. No nucleotide variations were identified in any isolates at the four E2 binding sites for HPV6 or HPV11, nor were any isolates found to be identical to the HPV6 lineage A or HPV11 sublineage A1 reference genomes. Overall, a high degree of sequence conservation was observed between isolates across each of the regions investigated for both HPV6 and HPV11. Genetic variants identified a slight association with HPV6 and anogenital lesions (p = 0.04). This study provides important information on the genetic diversity of circulating HPV 6 and HPV11 variants within the Australian population and supports the observation that the majority of HPV6 isolates cluster to the HPV6 sublineage B1 with anogenital lesions demonstrating an association with this sublineage (p = 0.02). Comparative analysis of Australian isolates for both HPV6 and HPV11 to those from other geographical regions based on the LCR revealed a high degree of sequence similarity throughout the world, confirming previous observations that there are no geographically specific variants for these HPV types. PMID:23691108

Comparison of DRY and WET vaginal swabs with cervical specimens in Roche Cobas 4800 HPV and Abbott RealTime High Risk HPV tests.

PubMed

Jun, Jae Kwan; Lim, Myong Cheol; Hwang, Sang-Hyun; Shin, Hye Young; Hwang, Na Rae; Kim, Yeon-Jin; Yoo, Chong Woo; Lee, Dong Ock; Joo, Jungnam; Park, Sang-Yoon; Lee, Do-Hoon

2016-06-01

Self-collected vaginal swab samples have been proposed as an alternative specimen collection method for human papillomavirus (HPV) DNA detection. Two vaginal swabs (a cone-shaped flocked swab (DRY) and a L-shape FLOQSwab with 2mL eNAT transport medium (WET)) were compared to standard cervical samples for HPV DNA testing. Additionally, they were also compared by using Roche Cobas 4800 HPV (Roche_HPV) and Abbott Real-time High Risk HPV (Abbott_HPV) tests. Ninety-six women were prospectively enrolled from the National Cancer Center in Korea between June and August 2015. WET and DRY vaginal swabs and cervical specimens were collected. Roche_HPV and Abbott_HPV tests were performed. The Roche_HPV test on cervical specimens was used as reference. The observed agreements (kappa) of Roche_HPV and Abbott_HPV between WET and DRY swabs were 89.6% (0.790, 95% confidence interval (95% CI): 0.667-0.913) and 91.7% (0.833, 95%CI: 0.723-0.943), respectively. No statistical difference was observed between WET and DRY swabs (p>0.05 for all comparisons). For HPV16/18, the sensitivity/specificity of Roche_HPV on the DRY and WET samples presented 93.8%/96.3% and 87.5%/97.5%, respectively. For other High Risk HPV (hrHPV), the sensitivity/specificity of Roche_HPV on the DRY and WET swabs presented 91.9%/91.5% and 97.3%/98.3, respectively. The sensitivity/specificity of the Abbott_HPV on the DRY and WET swabs were 93.8%/98.8%, 87.5%/98.8% for HPV16/18, and 91.9%/93.2%, 100.0%/93.2% for other hrHPV, respectively. HPV tests performed similarly when using vaginal DRY and WET swab samples. Using DRY and WET swabs to collect vaginal specimens could be an alternative to collecting cervical samples for HPV DNA testing. Copyright © 2016 Elsevier B.V. All rights reserved.

A Study of HPV Typing for the Management of HPV-Positive ASC-US Cervical Cytologic Results

PubMed Central

Schiffman, Mark; Vaughan, Laurence; Raine-Bennett, Tina R.; Castle, Philip E.; Katki, Hormuzd A.; Gage, Julia C.; Fetterman, Barbara; Befano, Brian; Wentzensen, Nicolas

2015-01-01

Background In US cervical screening, immediate colposcopy is recommended for women with HPV-positive ASC-US (equivocal) cytology. We evaluated whether partial typing by Onclarity™ (BD) might identify HPV-positive women with low enough CIN3+ risk to permit 1-year follow-up instead. Methods The NCI-Kaiser Permanente Northern California Persistence and Progression Cohort includes a subset of 13,890 women aged 21+ with HC2 (Qiagen)-positive ASC-US at enrollment; current median follow-up is 3.0 years. Using stratified random sampling, we typed 2,079 archived enrollment specimens including 329 women subsequently diagnosed with CIN3+, 563 with CIN2, and 1,187 with

A study of HPV typing for the management of HPV-positive ASC-US cervical cytologic results.

PubMed

Schiffman, Mark; Vaughan, Laurence M; Raine-Bennett, Tina R; Castle, Philip E; Katki, Hormuzd A; Gage, Julia C; Fetterman, Barbara; Befano, Brian; Wentzensen, Nicolas

2015-09-01

In US cervical screening, immediate colposcopy is recommended for women with HPV-positive ASC-US (equivocal) cytology. We evaluated whether partial typing by Onclarity™ (BD) might identify HPV-positive women with low enough CIN3+ risk to permit 1-year follow-up instead. The NCI-Kaiser Permanente Northern California Persistence and Progression cohort includes a subset of 13,890 women aged 21+ with HC2 (Qiagen)-positive ASC-US at enrollment; current median follow-up is 3.0years. Using stratified random sampling, we typed 2079 archived enrollment specimens including 329 women subsequently diagnosed with CIN3+, 563 with CIN2, and 1187 with

Human papillomavirus (HPV) types 16, 18, 31, 45 DNA loads and HPV-16 integration in persistent and transient infections in young women

PubMed Central

2010-01-01

Background HPV burden is a predictor for high-grade cervical intraepithelial neoplasia and cancer. The natural history of HPV load in young women being recently exposed to HPV is described in this paper. Methods A total of 636 female university students were followed for 2 years. Cervical specimens with HPV-16, -18, -31, or -45 DNA by consensus PCR were further evaluated with type-specific and β-globin real-time PCR assays. Proportional hazards regression was used to estimate hazard ratios (HR) of infection clearance. Generalized estimating equations assessed whether HPV loads was predictive of HPV infection at the subsequent visit. Results HPV loads were consistently higher among women <25 years old, and those who had multiple sex partners, multiple HPV type infections and smokers. HPV-16 integration was encountered only in one sample. Infection clearance was faster among women at lower tertiles of HPV-16 (HR = 2.8, 95%CI: 1.0-8.1), HPV-18 (HR = 3.5, 95%CI: 1.1-11.2) or combined (HR = 2.4, 95%CI: 1.8-6.2) DNA loads. The relationship between HPV-16 and HPV-18 DNA loads and infection clearance followed a clear dose-response pattern, after adjusting for age and number of sexual partners. GEE Odds Ratios for HPV persistence of the middle and upper tertiles relative to the lower tertile were 2.7 and 3.0 for HPV-16 and 3.8 and 39.1 for HPV-18, respectively. There was no association between HPV-31 or -45 DNA loads and persistence. Conclusions The association between HPV load and persistence is not uniform across high-risk genital genotypes. HPV-16 integration was only rarely demonstrated in young women. PMID:21070660

Comparing human papillomavirus prevalences in women with normal cytology or invasive cervical cancer to rank genotypes according to their oncogenic potential: a meta-analysis of observational studies

PubMed Central

2013-01-01

Background Mucosal human papillomavirus (HPV) infection is a necessary cause of cervical cancer. Vaccine and non-vaccine genotype prevalences may change after vaccine introduction. Therefore, it appears essential to rank HPV genotypes according to their oncogenic potential for invasive cervical cancer, independently of their respective prevalences. Methods We performed meta-analyses of published observational studies and estimated pooled odds ratios with random-effects models for 32 HPV genotypes, using HPV-16 as the reference. Results Twenty-seven studies yielded 9,252 HPV-infected women: 2,902 diagnosed with invasive cervical cancer and 6,350 with normal cytology. Expressed as (odds ratio [95% confidence interval]), HPV-18 (0.63 [0.51, 0.78]) ranked closest to HPV-16, while other genotypes showed continuously decreasing relative oncogenic potentials: HPV-45 (0.35 [0.22, 0.55]), HPV-69 (0.28 [0.09, 0.92]), HPV-58 (0.24 [0.15, 0.38]), HPV-31 (0.22 [0.14, 0.35]), HPV-33 (0.22 [0.12, 0.38]), HPV-34 (0.21 [0.06, 0.80]), HPV-67 (0.21 [0.06, 0.67]), HPV-39 (0.17 [0.09, 0.30]), HPV-59 (0.17 [0.09, 0.31]), HPV-73 (0.16 [0.06, 0.41]), and HPV-52 (0.16 [0.11, 0.23]). Conclusions Our results support the markedly higher oncogenic potentials of HPV-16 and -18, followed by HPV-31, -33, -39, -45, -52, -58 and -59, and highlight the need for further investigation of HPV-34, -67, -69 and -73. Overall, these findings could have important implications for the prevention of cervical cancer. PMID:23941096

Human Papillomavirus-associated oropharyngeal cancer: an observational study of diagnosis, prevalence and prognosis in a UK population

PubMed Central

2013-01-01

Background The incidence of Human Papillomavirus (HPV) associated oropharyngeal cancer (OPC) is increasing. HPV-associated OPC appear to have better prognosis than HPV-negative OPC. The aim of this study was to robustly determine the prevalence of HPV-positive OPC in an unselected UK population and correlate HPV positivity with clinical outcome. Methods HPV testing by GP5+/6+ PCR, In Situ Hybridisation (ISH) and p16 immunohistochemistry (IHC) was performed on 138 OPCs diagnosed in South Wales (UK) between 2001–06. Kaplan-Meier analysis was used to correlate HPV status with clinical outcome. Results Using a composite definition of HPV positivity (HPV DNA and p16 overexpression), HPV was detected in 46/83 (55%) samples where DNA quality was assured. Five year overall survival was 75.4% (95% CI: 65.2 to 85.5) in HPV-positives vs 25.3% (95% CI: 14.2 to 36.4) in HPV negatives, corresponding to a 78% reduction in death rate (HR 0.22, p < 0.001). HPV-positives had less locoregional recurrence but second HPV-positive Head and Neck primaries occurred. Poor quality DNA in fixed pathological specimens reduced both HPV prevalence estimates and the prognostic utility of DNA-based HPV testing methods. As a single marker, p16 was least affected by sample quality and correlated well with prognosis, although was not sufficient on its own for accurate HPV prevalence reporting. Conclusions This study highlights the significant burden of OPC associated with HPV infection. HPV positive cases are clinically distinct from other OPC, and are associated with significantly better clinical outcomes. A composite definition of HPV positivity should be used for accurate prevalence reporting and up-front DNA quality assessment is recommended for any DNA-based HPV detection strategy. PMID:23634887

Optimized Hyper Beamforming of Linear Antenna Arrays Using Collective Animal Behaviour

PubMed Central

Ram, Gopi; Mandal, Durbadal; Kar, Rajib; Ghoshal, Sakti Prasad

2013-01-01

A novel optimization technique which is developed on mimicking the collective animal behaviour (CAB) is applied for the optimal design of hyper beamforming of linear antenna arrays. Hyper beamforming is based on sum and difference beam patterns of the array, each raised to the power of a hyperbeam exponent parameter. The optimized hyperbeam is achieved by optimization of current excitation weights and uniform interelement spacing. As compared to conventional hyper beamforming of linear antenna array, real coded genetic algorithm (RGA), particle swarm optimization (PSO), and differential evolution (DE) applied to the hyper beam of the same array can achieve reduction in sidelobe level (SLL) and same or less first null beam width (FNBW), keeping the same value of hyperbeam exponent. Again, further reductions of sidelobe level (SLL) and first null beam width (FNBW) have been achieved by the proposed collective animal behaviour (CAB) algorithm. CAB finds near global optimal solution unlike RGA, PSO, and DE in the present problem. The above comparative optimization is illustrated through 10-, 14-, and 20-element linear antenna arrays to establish the optimization efficacy of CAB. PMID:23970843

Comprehensive mapping of the human papillomavirus (HPV) DNA integration sites in cervical carcinomas by HPV capture technology.

PubMed

Liu, Ying; Lu, Zheming; Xu, Ruiping; Ke, Yang

2016-02-02

Integration of human papillomavirus (HPV) DNA into the host genome can be a driver mutation in cervical carcinoma. Identification of HPV integration at base resolution has been a longstanding technical challenge, largely due to sensitivity masking by HPV in episomes or concatenated forms. The aim was to enhance the understanding of the precise localization of HPV integration sites using an innovative strategy. Using HPV capture technology combined with next generation sequencing, HPV prevalence and the exact integration sites of the HPV DNA in 47 primary cervical cancer samples and 2 cell lines were investigated. A total of 117 unique HPV integration sites were identified, including HPV16 (n = 101), HPV18 (n = 7), and HPV58 (n = 9). We observed that the HPV16 integration sites were broadly located across the whole viral genome. In addition, either single or multiple integration events could occur frequently for HPV16, ranging from 1 to 19 per sample. The viral integration sites were distributed across almost all the chromosomes, except chromosome 22. All the cervical cancer cases harboring more than four HPV16 integration sites showed clinical diagnosis of stage III carcinoma. A significant enrichment of overlapping nucleotides shared between the human genome and HPV genome at integration breakpoints was observed, indicating that it may play an important role in the HPV integration process. The results expand on knowledge from previous findings on HPV16 and HPV18 integration sites and allow a better understanding of the molecular basis of the pathogenesis of cervical carcinoma.

Multiple Human Papillomavirus Infection Is Associated with High-Risk Infection in Male Genital Warts in Ulsan, Korea

PubMed Central

Moon, Kyung Hyun; Yang, Sung-Hak; Roh, Min Cheol; Lee, Sang Hoon; Kim, Je Won; Kim, In Kyu; Roh, Kyoung Ho

2016-01-01

Further understanding of male human papillomavirus (HPV) infection is necessary to prevent infection in men, as well as transmission to women. In our current study, we investigated patterns of HPV infection and genotype distributions in male genital warts using the Anyplex II HPV28 Detection kit. We reviewed the medical records of 80 male patients who presented to 5 neighborhood clinics in Ulsan, Korea, for the treatment of genital warts between April 2014 and January 2015. All patients underwent HPV genotyping. The prevalence and characteristics of HPV infection were analyzed, and the patterns of HPV infection according to age were assessed. Among the study patients, 13 (16.3%) were negative for HPV infection, 46 (57.3%) were infected with low-risk HPV, and 21 (26.3%) were infected with high-risk HPV. Patients with multiple HPV infection were more likely to have high-risk HPV infection (P = 0.001). The prevalence of HPV infection was much higher in samples obtained by tissue excision due to a definite lesion (P = 0.001). There were no differences in high-risk HPV infection (P = 0.459), multiple HPV infection (P = 0.185), and recurrence at diagnosis (P = 0.178) according to age. HPV-6 and HPV-11 were the most common type overall (39.7% and 13.8%, respectively). HPV-16 and HPV-18 were the most common high-risk infections (both 3.4%). HPV infection is not only commonly encountered in male genital warts, but is also accompanied by high-risk HPV and multiple infections. PMID:26955236

HPV SEROSTATUS PRE- AND POST-VACCINATION IN A RANDOMIZED PHASE II PREPAREDNESS TRIAL AMONG YOUNG WESTERN CAPE, SOUTH AFRICAN WOMEN: THE EVRI TRIAL.

PubMed

Sudenga, Staci L; Torres, B Nelson; Botha, Matthys H; Zeier, Michele; Abrahamsen, Martha E; Glashoff, Richard H; Engelbrecht, Susan; Schim Van der Loeff, Maarten F; Van der Laan, Louvina E; Kipping, Siegfried; Taylor, Douglas; Giuliano, Anna R

2017-06-01

HPV antibodies are a marker of past exposure to the virus. Our objective was to assess HPV serostatus pre- and post-vaccination among HIV-negative women. Women aged 16-24 years old were randomized in a placebo controlled trial utilizing the 4-valent HPV (4vHPV) vaccine (NCT01489527, clinicaltrials.gov). Participants (n=389) received the 4vHPV vaccine or placebo following a three dose schedule. Sera were collected at Day 1 and Month 7 for assessment of HPV 6, 11, 16, and 18 neutralizing antibody levels using a multiplex competitive Luminex immunoassay (Merck) based on detecting the L1 capsid antigen for each HPV type. Seroprevalence was 73% for HPV6, 47% for HPV11, 33% for HPV16, and 44% for HPV18. Seroprevalence for any HPV type did not significantly differ by age or lifetime number of partners. The majority of participants (64%) had two or more 4vHPV antibodies present at enrollment and 12% had antibodies to all four. Among women in the vaccine arm, those that were seropositive for HPV16 at enrollment had higher titers at month 7 compared to women that were seronegative for HPV16 at enrollment; this trend holds for the other HPV types as well. Seroconversion among baseline seronegative participants in the placebo group ranged from 5% for HPV16 to 23% for HPV6. HPV seroprevalence was high in this population, emphasizing the need to vaccinate prior to sexual debut.

Multiple Human Papillomavirus Infection Is Associated with High-Risk Infection in Male Genital Warts in Ulsan, Korea.

PubMed

Kwon, Taekmin; Moon, Kyung Hyun; Yang, Sung-Hak; Roh, Min Cheol; Lee, Sang Hoon; Kim, Je Won; Kim, In Kyu; Roh, Kyoung Ho; Park, Sungchan

2016-03-01

Further understanding of male human papillomavirus (HPV) infection is necessary to prevent infection in men, as well as transmission to women. In our current study, we investigated patterns of HPV infection and genotype distributions in male genital warts using the Anyplex II HPV28 Detection kit. We reviewed the medical records of 80 male patients who presented to 5 neighborhood clinics in Ulsan, Korea, for the treatment of genital warts between April 2014 and January 2015. All patients underwent HPV genotyping. The prevalence and characteristics of HPV infection were analyzed, and the patterns of HPV infection according to age were assessed. Among the study patients, 13 (16.3%) were negative for HPV infection, 46 (57.3%) were infected with low-risk HPV, and 21 (26.3%) were infected with high-risk HPV. Patients with multiple HPV infection were more likely to have high-risk HPV infection (P = 0.001). The prevalence of HPV infection was much higher in samples obtained by tissue excision due to a definite lesion (P = 0.001). There were no differences in high-risk HPV infection (P = 0.459), multiple HPV infection (P = 0.185), and recurrence at diagnosis (P = 0.178) according to age. HPV-6 and HPV-11 were the most common type overall (39.7% and 13.8%, respectively). HPV-16 and HPV-18 were the most common high-risk infections (both 3.4%). HPV infection is not only commonly encountered in male genital warts, but is also accompanied by high-risk HPV and multiple infections.

Microstrip antenna developments at JPL

NASA Technical Reports Server (NTRS)

Huang, John

1991-01-01

The in-house development of microstrip antennas, initiated in 1981, when a spaceborne lightweight and low-profile planar array was needed for a satellite communication system, is described. The work described covers the prediction of finite-ground-plane effects by the geometric theory of diffraction, higher-order-mode circularly polarized circular patch antennas, circularly polarized microstrip arrays with linearly polarized elements, an impedance-matching teardrop-shaped probe feed, a dual-polarized microstrip array with high isolation and low cross-polarization, a planar microstrip Yagi array, a microstrip reflectarray, a Ka-band MMIC array, and a series-fed linear arrays.

Morphometric evaluation and nonclassical criteria for the diagnosis of HPV infection and cytological atypia in cervical samples.

PubMed

Sana, Dandara Emery Morais; Mayrink de Miranda, Priscila; Pitol, Bruna Caroline Vieira; Moran, Mariana Soares; Silva, Nayara Nascimento Toledo; Guerreiro da Silva, Ismael Dali Cotrim; de Cássia Stocco, Rita; Beçak, Willy; Lima, Angélica Alves; Carneiro, Cláudia Martins

2013-09-01

Herein, we evaluated cervical samples from normal tissue or HPV-infected tissue, to determine if the relative nuclear/cytoplasmic ratio (NA/CA) and the presence of nonclassical cytological criteria are a novel cytological criterion for the diagnosis of HPV. Significantly, larger NA/CA ratios were found for the HPV-ATYPIA+ and HPV+ATYPIA+ groups compared with HPV-ATYPIA- group, regardless of collection method. For the samples collected with a spatula, only three samples from the HPV-ATIPIA- group showed four or more nonclassical parameters (i.e., were positive), while a larger number of the samples in the HPV-ATYPIA+, HPV+ATYPIA-, and HPV+ATYPIA+ groups were positive (13, 4, and 13 samples, respectively). Among those collected with a brush, no sample showed four or more nonclassical criteria in the HPV-ATYPIA- group, while a number of samples were positive in the HPV-ATYPIA+, HPV+ATYPIA-, and HPV+ATYPIA+ groups (4, 3, and 4 samples, respectively). HPV infection was associated with significant morphometrical changes; no increase in the NA/CA ratio was found in the HPV+ATYPIA- samples, compared with the HPV-ATIPIA- samples collected with either a spatula or a brush. In conclusion, by including nonclassical cytological criteria into the patient diagnosis, we were able to reduce the number of false negative and false positive HPV diagnoses made using conventional cytology alone. Copyright © 2013 Wiley Periodicals, Inc.

[Prevalence of human papillomavirus in the pubic hair follicles of healthy men and male patients with genital warts].

PubMed

Wang, You-bao; Han, Tao; Zhao, Chun-xiong

2010-09-01

Human papillomavirus (HPV) commonly exists in healthy individuals, but its prevalence in the pubic hair follicles is not yet clear, nor is the relationship between HPV infection in the pubic hair follicles and the recurrence of genital warts in men. This study aimed to investigate HPV infection in the pubic hair follicles of healthy men and patients with genital warts, and to look into the correlation of HPV infection with recurrent genital warts. We included in this study 122 healthy men aged 21-80 years and 86 male patients with genital warts aged 24-61 years, detected HPV in their pubic hair follicles by PCR, and made comparative analysis of the data obtained from the two groups. The positive rate of HPV in the pubic hair follicles of the healthy males was 17.21% (21/122), including 15 cases of HPV6, 4 HPV11, 1 non-HPV6/11 and 1 the mixed type (both HPV6 and HPV11), while that of the genital wart patients was 32.55% (28/86), including 17 cases of HPV6, 7 HPV11, 2 non-HPV6/11 and 2 the mixed type. The incidence of HPV infection is higher in patients with genital warts than in healthy men, while the types of HPV involved are basically the same in the two groups, mainly HPV6 and HPV11.

Human papillomavirus and oral cancer: a primer for dental public health professionals.

PubMed

Chattopadhyay, A; Weatherspoon, D; Pinto, A

2015-06-01

There is strong evidence for causal association between human papillomavirus (HPV) and cervical cancer, evidence of association of HPV and oropharyngeal cancer is beginning to mount. To review the HPV-oral cancer literature for a comprehensive assessment of the issues involved. Literature search conducted using PubMed, Google Scholar and Google search engine. Both available HPV vaccines are efficacious and safe although expensive. Policy for mandatory HPV vaccination for cervical prevention is mired in political issues stemming from negative cost-effectiveness balance. Dental professionals are not ready to discuss the role of HPV vaccine in cancer prevention. This review discusses the impact of HPV on cervical cancer, transmission of HPV among humans, impact of HPV in oral health, and its plausible role in oral and oropharyngeal cancer, prevention of HPV transmission, available vaccines against HPV, testing, cost, policy and use of HPV vaccines internationally and dentists readiness related to HPV associated health communication. Given the mounting literature on the association between HPV and oropharyngeal cancer, the dental community must be prepared to answer patients' HPV-related questions and to educate patients about the role of HPV as a risk factor for oral and oropharyngeal cancers.

Human papillomavirus types in invasive cervical cancer specimens from Turkey.

PubMed

Usubütün, Alp; Alemany, Laia; Küçükali, Türkan; Ayhan, Ali; Yüce, Kunter; de Sanjosé, Silvia; Font, Rebeca; Lloveras, Belen; Klaustermeier, Joellen; Quint, Wim; Muñoz, Nubia; Bosch, Francesc Xavier

2009-11-01

The main aim of the study is to describe the human papillomavirus (HPV) type-specific distribution in invasive cervical cancer (ICC) specimens from Turkey. Paraffin-embedded ICC specimens were identified from the histopathologic archives of the Hacettepe University Medical School in Turkey. HPV detection was carried out through amplification of HPV DNA by a SPF-10 broad-spectrum primer polymerase chain reaction and subsequently followed by DNA enzyme immunoassay and genotyping by LiPA25 (version 1). Two hundred seventy-seven ICC cases diagnosed between 1993 and 2004 were retrieved. After histologic evaluation and human beta-globin gene analysis for sample quality, 248 cases were considered suitable for HPV/DNA testing. HPV prevalence was 93.5% (232/248; 95% confidence interval: 90.5%-96.6%). The five most common HPV types identified as single types among HPV-positive cases were HPV16 (64.7%), HPV18 (9.9%), HPV45 (9.9%), HPV31 (3.0%), and HPV33 (2.2%). The study shows that in Turkey, HPV16/HPV18 accounted for 75.4% (95% confidence interval: 69.9%-81.0%) of HPV-positive ICC cases. This information is essential to evaluate the potential impact of the HPV vaccines in the country.

Human papillomavirus in normal conjunctival tissue and in conjunctival papilloma: types and frequencies in a large series.

PubMed

Sjö, Nicolai Christian; von Buchwald, Christian; Cassonnet, Patricia; Norrild, Bodil; Prause, Jan Ulrik; Vinding, Troels; Heegaard, Steffen

2007-08-01

To examine conjunctival papilloma and normal conjunctival tissue for the presence of human papillomavirus (HPV). Archival paraffin wax-embedded tissue from 165 conjunctival papillomas and from 20 histological normal conjunctival biopsy specimens was analysed for the presence of HPV by PCR. Specimens considered HPV positive using consensus primers, but with a negative or uncertain PCR result using type-specific HPV probes, were analysed with DNA sequencing. HPV was present in 86 of 106 (81%) beta-globin-positive papillomas. HPV type 6 was positive in 80 cases, HPV type 11 was identified in 5 cases and HPV type 45 was present in a single papilloma. All the 20 normal conjunctival biopsy specimens were beta-globin positive and HPV negative. There is a strong association between HPV and conjunctival papilloma. The study presents the largest material of conjunctival papilloma investigated for HPV and the first investigation of HPV in normal conjunctival tissue. HPV types 6 and 11 are the most common HPV types in conjunctival papilloma. This also is the first report of HPV type 45 in conjunctival papilloma.

Human Papillomavirus (HPV) L1 Serum Antibodies and the Risk of Subsequent Oral HPV Acquisition in Men: The HIM Study.

PubMed

Pierce Campbell, Christine M; Viscidi, Raphael P; Torres, B Nelson; Lin, Hui-Yi; Fulp, William; Abrahamsen, Martha; Lazcano-Ponce, Eduardo; Villa, Luisa L; Kreimer, Aimée R; Giuliano, Anna R

2016-07-01

The role of antibody-mediated immunity in preventing newly acquired oral human papillomavirus (HPV) is not well understood. Among 1618 men participating in the HPV Infection in Men (HIM) Study, we evaluated oral rinses for HPV DNA and baseline sera for HPV-6, -11, -16, and -18 L1 antibodies. Thirty percent of men (486) were seropositive for ≥1 HPV type, and 25 men developed incident oral HPV infection (HPV-6 was detected in 7, HPV-11 in 0, HPV-16 in 17, and HPV-18 in 1). Cox models revealed that men with circulating antibodies to HPV-6, -11, -16, or -18 were not less likely to acquire type-specific oral HPV than men without antibodies (hazard ratio for the risk of acquiring HPV-6, -11, -16, or -18, 1.63; 95% confidence interval, .56-4.76). © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Anogenital warts contain several distinct species of human papillomavirus.

PubMed Central

Krzyzek, R A; Watts, S L; Anderson, D L; Faras, A J; Pass, F

1980-01-01

Anogenital warts from 26 patients were examined for the presence of human papillomavirus (HPV). Although no whole, intact virus could be identified, varying amounts of nonintegrated HPV DNA were detected in 18 tissue specimens (70%) by employing both an agarose gel-ethidium bromide staining method and the Southern blot hybridization procedure. When hybridization analysis was performed under stringent conditions, six anogenital warts were observed to contain HPV genomic sequences related to either of the cutaneous viruses HPV type 1 (HPV-1) or HPV-2. In 12 tissue samples lacking sequence homology to either HPV-1 or HPV-2 under stringent conditions, HPV-related sequences were detected when the hybridization was performed under less stringent conditions, indicating that an HPV distinct from both HPV-1 and HPV-2 is also associated with these lesions. This anogenital HPV also appeared to be distinct from the other characterized types of HPV. These data indicate that at least three HPVs are associated with anogenital wart disease. Images PMID:6255208

Current State in the Development of Candidate Therapeutic HPV Vaccines

PubMed Central

Yang, Andrew; Jeang, Jessica; Cheng, Kevin; Cheng, Ting; Yang, Benjamin; Wu, T.-C.; Hung, Chien-Fu

2016-01-01

Summary The identification of human papillomavirus (HPV) as an etiological factor for HPV-associated malignancies creates the opportunity to control these cancers through vaccination. Currently, available preventive HPV vaccines have not yet demonstrated strong evidences for therapeutic effects against established HPV infections and lesions. Furthermore, HPV infections remain extremely common. Thus, there is urgent need for therapeutic vaccines to treat existing HPV infections and HPV-associated diseases. Therapeutic vaccines differ from preventive vaccines in that they are aimed at generating cell-mediated immunity rather than neutralizing antibodies. The HPV-encoded early proteins, especially oncoproteins E6 and E7, form ideal targets for therapeutic HPV vaccines since they are consistently expressed in HPV-associated malignancies and precancerous lesions, playing crucial roles in the generation and maintenance of HPV-associated disease. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we review strategies to enhance vaccine efficacy and the latest clinical trials on therapeutic HPV vaccines. PMID:26901118

Cervical and Anal Human Papillomavirus Infection in Adult Women in American Samoa

PubMed Central

Hernandez, Brenda Y.; Ka’opua, Lana S.; Scanlan, Luana; Ah Ching, John; Kamemoto, Lori E.; Thompson, Pamela J.; Zhu, Xuemei; Shvetsov, Yurii B.; Tofaeono, Jennifer; Williams, Victor Tofaeono

2015-01-01

The prevalence of cervical and anal human papillomavirus (HPV) and risk factors associated with infections were evaluated in a cross-sectional study of 211 adult women in American Samoa. Overall, 53% of women reported ever having a Pap smear. Cervical and anal HPV was detected in 10% and 16% of women, respectively; 4% of women had concurrent cervical and anal HPV. The most common cervical genotypes were HPV 6, HPV 16, and HPV 53. Cutaneous HPV types were detected in 40% of anal infections. Cervical HPV infection was associated with anal HPV (age-adjusted odds ratio = 3.32, 1.10–10.00). After age adjustment, cervical HPV was associated with being unmarried, postsecondary education, hot running water at home, multiple sexual partners, nulliparity, condom use, and other contraceptive methods. In multivariate analyses, only age remained associated with cervical HPV and anal HPV. Cervical and anal HPV was more prevalent among younger women; only anal HPV was detected in older women. PMID:22652246

Return on Investment: A Fuller Assessment of the Benefits and Cost Savings of the US Publicly Funded Family Planning Program

PubMed Central

Frost, Jennifer J; Sonfield, Adam; Zolna, Mia R; Finer, Lawrence B

2014-01-01

Context Each year the United States’ publicly supported family planning program serves millions of low-income women. Although the health impact and public-sector savings associated with this program's services extend well beyond preventing unintended pregnancy, they never have been fully quantified. Methods Drawing on an array of survey data and published parameters, we estimated the direct national-level and state-level health benefits that accrued from providing contraceptives, tests for the human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs), Pap tests and tests for human papillomavirus (HPV), and HPV vaccinations at publicly supported family planning settings in 2010. We estimated the public cost savings attributable to these services and compared those with the cost of publicly funded family planning services in 2010 to find the net public-sector savings. We adjusted our estimates of the cost savings for unplanned births to exclude some mistimed births that would remain publicly funded if they had occurred later and to include the medical costs for births through age 5 of the child. Findings In 2010, care provided during publicly supported family planning visits averted an estimated 2.2 million unintended pregnancies, including 287,500 closely spaced and 164,190 preterm or low birth weight (LBW) births, 99,100 cases of chlamydia, 16,240 cases of gonorrhea, 410 cases of HIV, and 13,170 cases of pelvic inflammatory disease that would have led to 1,130 ectopic pregnancies and 2,210 cases of infertility. Pap and HPV tests and HPV vaccinations prevented an estimated 3,680 cases of cervical cancer and 2,110 cervical cancer deaths; HPV vaccination also prevented 9,000 cases of abnormal sequelae and precancerous lesions. Services provided at health centers supported by the Title X national family planning program accounted for more than half of these benefits. The gross public savings attributed to these services totaled approximately $15.8 billion—$15.7 billion from preventing unplanned births, $123 million from STI/HIV testing, and $23 million from Pap and HPV testing and vaccines. Subtracting $2.2 billion in program costs from gross savings resulted in net public-sector savings of $13.6 billion. Conclusions Public expenditures for the US family planning program not only prevented unintended pregnancies but also reduced the incidence and impact of preterm and LBW births, STIs, infertility, and cervical cancer. This investment saved the government billions of public dollars, equivalent to an estimated taxpayer savings of $7.09 for every public dollar spent. PMID:25314928

[Distribution and associated factors of high-risk HPV genotypes infection among HPV-positive women who participated cervical screening test in Shenzhen, 2014-2016, China].

PubMed

Wang, Y Y; Lin, W; Wu, B; Yuan, S X; Yao, J L; Zhao, X S; Chen, B; Qiao, Y L; Zhao, F H; Chen, W; Hu, S Y; Liu, Z H

2018-05-06

Objective: To analyze the distribution and associated factors of high-risk genotypes of HPV in cervical infection among women in Shenzhen. Methods: The information on sociodemographic characteristics and HPV genotypes of HPV-positive women who participated cervical screening test from January 2014 to December 2016 was downloaded from Shenzhen Maternity and Child Healthcare Management Information System. According to the pathogenicity, the high-risk HPV genotypes were divided into 15 types including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68; and there were 6 low-risk genotypes including HPV 6, 11, 42, 43, 44, and 81. Chi-square tests were applied to compare the proportions of high-risk HPV infection among women who had different sociodemographic characteristics. A non-conditional logistic regression model was used to analyze the associated factors for high-risk HPV infection. Results: In total, all HIV positives received HPV genotyping, with an average age of (38.08±9.38) years old. There were 9 979 (93.9%) high-risk and 645 (6.1%) low-risk HPV infections. The proportions of HPV infections for high-risk type in each year were 91.5%, 93.8%, and 95.6%, increasing with the screening years (χ(2)=54.79, P< 0.001). Multivariate logistic regression analysis showed that compared with women younger than 25 years old, women in other age groups (at age 26 to 30 years, 31 to 35 years, 36 to 40 years, 41 to 45 years, and 50 years or older) had increased risks of high-risk HPV infection, with OR (95 %CI ) of 1.67 (1.20-2.31), 1.49 (1.09-2.03), 1.71 (1.23-2.37), 1.65 (1.19-2.31), and 1.84 (1.26-2.67), respectively; compared with the married, single women had a decreased risk of high-risk HPV infection ( OR (95 %CI ): 0.71 (0.50-1.00)); women received HPV testing in 2015 and 2016 showed higher risk of high-risk HPV infection than those in 2014 ( OR (95 %CI ): 1.43 (1.17-1.74) and 2.03 (1.68-2.46)). The 5 most common HPV genotypes were HPV52 (25.1%, 2 670 cases), followed by HPV16 (19.2%, 2 041 cases), HPV58 (13.3%, 1 413 cases), HPV18 (9.9%, 1 048 cases), and HPV51 (9.3%, 993 cases). Conclusion: Age, marital status, and screening year were associated with high-risk HPV infections. Besides HPV16 and HPV18, the prevention and control on HPV infections for HPV52, HPV58, and HPV51 should be prioritized in Shenzhen area.

A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women.

PubMed

Joura, Elmar A; Giuliano, Anna R; Iversen, Ole-Erik; Bouchard, Celine; Mao, Constance; Mehlsen, Jesper; Moreira, Edson D; Ngan, Yuen; Petersen, Lone Kjeld; Lazcano-Ponce, Eduardo; Pitisuttithum, Punnee; Restrepo, Jaime Alberto; Stuart, Gavin; Woelber, Linn; Yang, Yuh Cheng; Cuzick, Jack; Garland, Suzanne M; Huh, Warner; Kjaer, Susanne K; Bautista, Oliver M; Chan, Ivan S F; Chen, Joshua; Gesser, Richard; Moeller, Erin; Ritter, Michael; Vuocolo, Scott; Luxembourg, Alain

2015-02-19

The investigational 9-valent viruslike particle vaccine against human papillomavirus (HPV) includes the HPV types in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58). Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age. We performed a randomized, international, double-blind, phase 2b-3 study of the 9vHPV vaccine in 14,215 women. Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6. Serum was collected for analysis of antibody responses. Swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue were obtained and used for HPV DNA testing, and liquid-based cytologic testing (Papanicolaou testing) was performed regularly. Tissue obtained by means of biopsy or as part of definitive therapy (including a loop electrosurgical excision procedure and conization) was tested for HPV. The rate of high-grade cervical, vulvar, or vaginal disease irrespective of HPV type (i.e., disease caused by HPV types included in the 9vHPV vaccine and those not included) in the modified intention-to-treat population (which included participants with and those without prevalent infection or disease) was 14.0 per 1000 person-years in both vaccine groups. The rate of high-grade cervical, vulvar, or vaginal disease related to HPV-31, 33, 45, 52, and 58 in a prespecified per-protocol efficacy population (susceptible population) was 0.1 per 1000 person-years in the 9vHPV group and 1.6 per 1000 person-years in the qHPV group (efficacy of the 9vHPV vaccine, 96.7%; 95% confidence interval, 80.9 to 99.8). Antibody responses to HPV-6, 11, 16, and 18 were noninferior to those generated by the qHPV vaccine. Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group. The 9vHPV vaccine prevented infection and disease related to HPV-31, 33, 45, 52, and 58 in a susceptible population and generated an antibody response to HPV-6, 11, 16, and 18 that was noninferior to that generated by the qHPV vaccine. The 9vHPV vaccine did not prevent infection and disease related to HPV types beyond the nine types covered by the vaccine. (Funded by Merck; ClinicalTrials.gov number, NCT00543543).

Human Papillomavirus (HPV) infection in pregnant women and mother-to-child transmission of genital HPV genotypes: a prospective study in Spain

PubMed Central

2009-01-01

Background Studies on HPV infection in pregnant women and HPV transmission to the child have yielded inconsistent results. Methods To estimate mother-to-child HPV transmission we carried out a prospective cohort study that included 66 HPV-positive and 77 HPV-negative pregnant women and their offspring attending a maternity hospital in Barcelona. To estimate HPV prevalence and genotype distribution in pregnancy we also carried out a related screening survey of cervical HPV-DNA detection among 828 pregnant women. Cervical cells from the mother were collected at pregnancy (mean of 31 weeks) and at the 6-week post-partum visit. Exfoliated cells from the mouth and external genitalia of the infants were collected around birth, at the 6-week post-partum visit, and around 3, 6, 12, and 24 months of age. All samples were tested for HPV using PCR. Associations between potential determinants of HPV infection in pregnant women and of HPV positivity in infants were also explored by logistic regression modelling. Results Overall cervical HPV-DNA detection in pregnant women recruited in the HPV screening survey was 6.5% (54/828). Sexual behavior-related variables, previous histories of genital warts or sexually transmitted infections, and presence of cytological abnormalities were statistically significantly and positively associated with HPV DNA detection in pregnant women recruited in the cohort. At 418 infant visits and a mean follow-up time of 14 months, 19.7% of infants born to HPV-positive mothers and 16.9% of those born to HPV-negative mothers tested HPV positive at some point during infants' follow-up. The most frequently detected genotype both in infants and mothers was HPV-16, after excluding untyped HPV infections. We found a strong and statistically significant association between mother's and child's HPV status at the 6-week post-partum visit. Thus, children of mothers' who were HPV-positive at the post-partum visit were about 5 times more likely to test HPV-positive than children of corresponding HPV-negative mothers (p = 0.02). Conclusion This study confirms that the risk of vertical transmission of HPV genotypes is relatively low. HPV persistence in infants is a rare event. These data also indicate that vertical transmission may not be the sole source of HPV infections in infants and provides partial evidence for horizontal mother-to-child HPV transmission. PMID:19473489

Human papillomavirus infection in females with normal cervical cytology: Genotyping and phylogenetic analysis among women in Punjab, Pakistan.

PubMed

Aziz, Hafsa; Iqbal, Huma; Mahmood, Humera; Fatima, Shazia; Faheem, Mohammad; Sattar, Areej Abdul; Tabassum, Sobia; Napper, Sanum; Batool, Syeda; Rasheed, Nuzhat

2018-01-01

Globally, cervical cancer is the fourth most common cancer in women and the seventh most common cancer overall, accounting for an estimated 300 000 annual deaths. Human papillomavirus (HPV) is the second most common cause of cervical cancer worldwide. HPV screening is not a common practice in Pakistan. The aim of this study was to determine the prevalence of HPV and HPV types in women with a normal cytology of the cervix living in the upper and lower regions of Punjab, Pakistan, and to analyze the risk factors for HPV in this region. PCR analysis was performed for 1011 female patients with a normal cytology of the cervix from various districts of Punjab Province, Pakistan. Risk factors for the acquisition of HPV were studied. High-risk HPV types (HPV16 and HPV18) were detected using the Abbott Real Time HR HPV test. To determine the genotype, partial L1 region sequences of HPV-positive samples were subjected to sequencing using MY/09/MY11 primers, and a phylogenetic tree was constructed using CLC software. The study found a 4.74% prevalence of HPV, with the most frequent HPV type found being the low-risk HPV6 (in 25% of infected individuals), followed by HPV55 (22.9%), HPV11 (20.8%), and high-risk types HPV45 (12.5%), HPV33 (8.33%), HPV18 (6.25%), and HPV16 (4.16%). Phylogenetic analysis of all HPV types in this study showed 80-99% nucleotide identity with types related to the same species. The sequences were clustered with China, India, Mexico, Iran, Slovenia, and Germany, showing the diversity in origin of the various genotypes prevalent in Pakistan. In this population with a normal cervical cytology, the prevalence of high-risk HPV types was very low. The major prevalent HPV genotype in Punjab Province of Pakistan was the low-risk HPV type 6, followed by HPV type 55. Sequencing of the partial L1 region suggested that the region was highly conserved in all reported sequences. This study highlights the need to conduct robust epidemiological studies in the region and to develop regular HPV screening so that the situation does not reach an alarming stage resulting in cervical cancer. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Natural history of progression of HPV infection to cervical lesion or clearance: analysis of the control arm of the large, randomised PATRICIA study.

PubMed

Jaisamrarn, Unnop; Castellsagué, Xavier; Garland, Suzanne M; Naud, Paulo; Palmroth, Johanna; Del Rosario-Raymundo, Maria Rowena; Wheeler, Cosette M; Salmerón, Jorge; Chow, Song-Nan; Apter, Dan; Teixeira, Julio C; Skinner, S Rachel; Hedrick, James; Szarewski, Anne; Romanowski, Barbara; Aoki, Fred Y; Schwarz, Tino F; Poppe, Willy A J; Bosch, F Xavier; de Carvalho, Newton S; Germar, Maria Julieta; Peters, Klaus; Paavonen, Jorma; Bozonnat, Marie-Cecile; Descamps, Dominique; Struyf, Frank; Dubin, Gary O; Rosillon, Dominique; Baril, Laurence

2013-01-01

The control arm of PATRICIA (PApilloma TRIal against Cancer In young Adults, NCT00122681) was used to investigate the risk of progression from cervical HPV infection to cervical intraepithelial neoplasia (CIN) or clearance of infection, and associated determinants. Women aged 15-25 years were enrolled. A 6-month persistent HPV infection (6MPI) was defined as detection of the same HPV type at two consecutive evaluations over 6 months and clearance as ≥2 type-specific HPV negative samples taken at two consecutive intervals of approximately 6 months following a positive sample. The primary endpoint was CIN grade 2 or greater (CIN2+) associated with the same HPV type as a 6MPI. Secondary endpoints were CIN1+/CIN3+ associated with the same HPV type as a 6MPI; CIN1+/CIN2+/CIN3+ associated with an infection of any duration; and clearance of infection. The analyses included 4825 women with 16,785 infections (3363 women with 6902 6MPIs). Risk of developing a CIN1+/CIN2+/CIN3+ associated with same HPV type as a 6MPI varied with HPV type and was significantly higher for oncogenic versus non-oncogenic types. Hazard ratios for development of CIN2+ were 10.44 (95% CI: 6.96-15.65), 9.65 (5.97-15.60), 5.68 (3.50-9.21), 5.38 (2.87-10.06) and 3.87 (2.38-6.30) for HPV-16, HPV-33, HPV-31, HPV-45 and HPV-18, respectively. HPV-16 or HPV-33 6MPIs had ~25-fold higher risk for progression to CIN3+. Previous or concomitant HPV infection or CIN1+ associated with a different HPV type increased risk. Of the different oncogenic HPV types, HPV-16 and HPV-31 infections were least likely to clear. Cervical infections with oncogenic HPV types increased the risk of CIN2+ and CIN3+. Previous or concomitant infection or CIN1+ also increased the risk. HPV-16 and HPV-33 have by far the highest risk of progression to CIN3+, and HPV-16 and HPV-31 have the lowest chance of clearance.

Clinicopathological Implications of Human Papilloma Virus (HPV) L1 Capsid Protein Immunoreactivity in HPV16-Positive Cervical Cytology

PubMed Central

Lee, Sung-Jong; Lee, Ah-Won; Kang, Chang-Suk; Park, Jong-Sup; Park, Dong-Choon; Ki, Eun-Young; Lee, Keun-Ho; Yoon, Joo-Hee; Hur, Soo-Young; Kim, Tae-Jung

2014-01-01

Background: The objective of this study was to investigate the expression of human papilloma virus (HPV) L1 capsid protein in abnormal cervical cytology with HPV16 infection and analyze its association with cervical histopathology in Korean women. Material and Methods: We performed immunocytochemistry for HPV L1 in 475 abnormal cervical cytology samples from patients with HPV16 infections using the Cytoactiv® HPV L1 screening set. We investigated the expression of HPV L1 in cervical cytology samples and compared it with the results of histopathological examination of surgical specimens. Results: Of a total of 475 cases, 188 (39.6%) were immunocytochemically positive and 287 (60.4%) negative for HPV L1. The immunocytochemical expression rates of HPV L1 in atypical squamous cells of unknown significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), and cancer were 21.8%, 59.7%, 19.1%, and 0.0%, respectively. LSIL exhibited the highest rate of HPV L1 positivity. Of a total of 475 cases, the multiple-type HPV infection rate, including HPV16, in HPV L1-negative cytology samples was 27.5%, which was significantly higher than that in HPV L1-positive cytology samples (p = 0.037). The absence of HPV L1 expression in ASCUS and LSIL was significantly associated with high-grade (≥cervical intraepithelial neoplasia [CIN] 2) than low-grade (≤CIN1) histopathology diagnoses (p < 0.05), but was not significantly different between HPV16 single and multiple-type HPV infections (p > 0.05). On the other hand, among 188 HPV L1-positive cases, 30.6% of multiple-type HPV infections showed high-grade histopathology diagnoses (≥CIN3), significantly higher than the percentage of HPV16 single infections (8.6%) (p = 0.0004) Conclusions: Our study demonstrates that the expression of HPV L1 is low in advanced dysplasia. Furthermore, the absence of HPV L1 in HPV16-positive low-grade cytology (i.e., ASCUS and LSIL) is strongly associated with high-grade histopathology diagnoses. The multiplicity of HPV infections may have an important role in high-grade histopathology diagnoses (≥CIN3) in HPV L1-positive cases. PMID:24396289

Natural History of Progression of HPV Infection to Cervical Lesion or Clearance: Analysis of the Control Arm of the Large, Randomised PATRICIA Study

PubMed Central

Jaisamrarn, Unnop; Castellsagué, Xavier; Garland, Suzanne M.; Naud, Paulo; Palmroth, Johanna; Del Rosario-Raymundo, Maria Rowena; Wheeler, Cosette M.; Salmerón, Jorge; Chow, Song-Nan; Apter, Dan; Teixeira, Julio C.; Skinner, S. Rachel; Hedrick, James; Szarewski, Anne; Romanowski, Barbara; Aoki, Fred Y.; Schwarz, Tino F.; Poppe, Willy A. J.; Bosch, F. Xavier; de Carvalho, Newton S.; Germar, Maria Julieta; Peters, Klaus; Paavonen, Jorma; Bozonnat, Marie-Cecile; Descamps, Dominique; Struyf, Frank; Dubin, Gary O.; Rosillon, Dominique; Baril, Laurence

2013-01-01

Background The control arm of PATRICIA (PApillomaTRIal against Cancer In young Adults, NCT00122681) was used to investigate the risk of progression from cervical HPV infection to cervical intraepithelial neoplasia (CIN) or clearance of infection, and associated determinants. Methods and Findings Women aged 15-25 years were enrolled. A 6-month persistent HPV infection (6MPI) was defined as detection of the same HPV type at two consecutive evaluations over 6 months and clearance as ≥2 type-specific HPV negative samples taken at two consecutive intervals of approximately 6 months following a positive sample. The primary endpoint was CIN grade 2 or greater (CIN2+) associated with the same HPV type as a 6MPI. Secondary endpoints were CIN1+/CIN3+ associated with the same HPV type as a 6MPI; CIN1+/CIN2+/CIN3+ associated with an infection of any duration; and clearance of infection. The analyses included 4825 women with 16,785 infections (3363 womenwith 6902 6MPIs). Risk of developing a CIN1+/CIN2+/CIN3+ associated with same HPV type as a 6MPI varied with HPV type and was significantly higher for oncogenic versus non-oncogenic types. Hazard ratios for development of CIN2+ were 10.44 (95% CI: 6.96-15.65), 9.65 (5.97-15.60), 5.68 (3.50-9.21), 5.38 (2.87-10.06) and 3.87 (2.38-6.30) for HPV-16, HPV-33, HPV-31, HPV-45 and HPV-18, respectively. HPV-16 or HPV-33 6MPIs had ~25-fold higher risk for progression to CIN3+. Previous or concomitant HPV infection or CIN1+ associated with a different HPV type increased risk. Of the different oncogenic HPV types, HPV-16 and HPV-31 infections were least likely to clear. Conclusions Cervical infections with oncogenic HPV types increased the risk of CIN2+ and CIN3+. Previous or concomitant infection or CIN1+ also increased the risk. HPV-16 and HPV-33 have by far the highest risk of progression to CIN3+, and HPV-16 and HPV-31 have the lowest chance of clearance. PMID:24260180

Chimeric L2-Based Virus-Like Particle (VLP) Vaccines Targeting Cutaneous Human Papillomaviruses (HPV).

PubMed

Huber, Bettina; Schellenbacher, Christina; Shafti-Keramat, Saeed; Jindra, Christoph; Christensen, Neil; Kirnbauer, Reinhard

2017-01-01

Common cutaneous human papillomavirus (HPV) types induce skin warts, whereas species beta HPV are implicated, together with UV-radiation, in the development of non-melanoma skin cancer (NMSC) in immunosuppressed patients. Licensed HPV vaccines contain virus-like particles (VLP) self-assembled from L1 major capsid proteins that provide type-restricted protection against mucosal HPV infections causing cervical and other ano-genital and oro-pharyngeal carcinomas and warts (condylomas), but do not target heterologous HPV. Experimental papillomavirus vaccines have been designed based on L2 minor capsid proteins that contain type-common neutralization epitopes, to broaden protection to heterologous mucosal and cutaneous HPV types. Repetitive display of the HPV16 L2 cross-neutralization epitope RG1 (amino acids (aa) 17-36) on the surface of HPV16 L1 VLP has greatly enhanced immunogenicity of the L2 peptide. To more directly target cutaneous HPV, L1 fusion proteins were designed that incorporate the RG1 homolog of beta HPV17, the beta HPV5 L2 peptide aa53-72, or the common cutaneous HPV4 RG1 homolog, inserted into DE surface loops of HPV1, 5, 16 or 18 L1 VLP scaffolds. Baculovirus expressed chimeric proteins self-assembled into VLP and VLP-raised NZW rabbit immune sera were evaluated by ELISA and L1- and L2-based pseudovirion (PsV) neutralizing assays, including 12 novel beta PsV types. Chimeric VLP displaying the HPV17 RG1 epitope, but not the HPV5L2 aa53-72 epitope, induced cross-neutralizing humoral immune responses to beta HPV. In vivo cross-protection was evaluated by passive serum transfer in a murine PsV challenge model. Immune sera to HPV16L1-17RG1 VLP (cross-) protected against beta HPV5/20/24/38/96/16 (but not type 76), while antisera to HPV5L1-17RG1 VLP cross-protected against HPV20/24/96 only, and sera to HPV1L1-4RG1 VLP cross-protected against HPV4 challenge. In conclusion, RG1-based VLP are promising next generation vaccine candidates to target cutaneous HPV infections.

Multisite HPV16/18 Vaccine Efficacy Against Cervical, Anal, and Oral HPV Infection

PubMed Central

Kreimer, Aimée R.; Schiffman, Mark; Herrero, Rolando; Wacholder, Sholom; Rodriguez, Ana Cecilia; Lowy, Douglas R.; Porras, Carolina; Schiller, John T.; Quint, Wim; Jimenez, Silvia; Safaeian, Mahboobeh; Struijk, Linda; Schussler, John; Hildesheim, Allan; Gonzalez, Paula

2016-01-01

Background: Previous Costa Rica Vaccine Trial (CVT) reports separately demonstrated vaccine efficacy against HPV16 and HPV18 (HPV16/18) infections at the cervical, anal, and oral regions; however, the combined overall multisite efficacy (protection at all three sites) and vaccine efficacy among women infected with HPV16 or HPV18 prior to vaccination are less known. Methods: Women age 18 to 25 years from the CVT were randomly assigned to the HPV16/18 vaccine (Cervarix) or a hepatitis A vaccine. Cervical, oral, and anal specimens were collected at the four-year follow-up visit from 4186 women. Multisite and single-site vaccine efficacies (VEs) and 95% confidence intervals (CIs) were computed for one-time detection of point prevalent HPV16/18 in the cervical, anal, and oral regions four years after vaccination. All statistical tests were two-sided. Results: The multisite woman-level vaccine efficacy was highest among “naïve” women (HPV16/18 seronegative and cervical HPV high-risk DNA negative at vaccination) (vaccine efficacy = 83.5%, 95% CI = 72.1% to 90.8%). Multisite woman-level vaccine efficacy was also demonstrated among women with evidence of a pre-enrollment HPV16 or HPV18 infection (seropositive for HPV16 and/or HPV18 but cervical HPV16/18 DNA negative at vaccination) (vaccine efficacy = 57.8%, 95% CI = 34.4% to 73.4%), but not in those with cervical HPV16 and/or HPV18 DNA at vaccination (anal/oral HPV16/18 VE = 25.3%, 95% CI = -40.4% to 61.1%). Concordant HPV16/18 infections at two or three sites were also less common in HPV16/18-infected women in the HPV vaccine vs control arm (7.4% vs 30.4%, P < .001). Conclusions: This study found high multisite vaccine efficacy among “naïve” women and also suggests the vaccine may provide protection against HPV16/18 infections at one or more anatomic sites among some women infected with these types prior to HPV16/18 vaccination. PMID:26467666

Molecular characterization, tissue tropism, and genetic variability of the novel Mupapillomavirus type HPV204 and phylogenetically related types HPV1 and HPV63

PubMed Central

Šterbenc, Anja; Hošnjak, Lea; Chouhy, Diego; Bolatti, Elisa M.; Oštrbenk, Anja; Seme, Katja; Kocjan, Boštjan J.; Luzar, Boštjan; Giri, Adriana A.; Poljak, Mario

2017-01-01

HPV204 is the only newly identified Mupapillomavirus (Mu-PV) type in more than a decade. To comprehensively characterize HPV204, we performed a detailed molecular analysis of the viral genome and evaluated its clinical relevance in comparison to the other Mu-PVs, HPV1 and HPV63. The 7,227-bp long genome of HPV204 exhibits typical genomic organization of Mu-PVs with eight open reading frames (ORFs) (E6, E7, E1, E2, E8, E4, L2, and L1). We developed three type-specific quantitative real-time PCRs and used them to test a representative collection (n = 1,006) of various HPV-associated benign and malignant neoplasms, as well as samples of clinically normal cutaneous, mucosal, and mucocutaneous origins. HPV204, HPV1, and HPV63 were detected in 1.1%, 2.7%, and 1.9% of samples tested, respectively, and were present in skin and mucosa, suggesting dual tissue tropism of all Mu-PVs. To evaluate the etiological role of Mu-PVs in the development of HPV-associated neoplasms, Mu-PV viral loads per single cell were estimated. HPV1 and HPV63 were present in high viral copy numbers in 3/43 and 1/43 cutaneous warts, respectively, and were identified as the most likely causative agents of these warts. HPV204 viral load was extremely low in a single HPV204-positive cutaneous wart (7.4 × 10−7 viral copies/cell). Hence, etiological association between HPV204 and the development of cutaneous warts could not be established. To the best of our knowledge, this is the first study to evaluate the genetic variability of Mu-PVs by sequencing complete LCR genomic regions of HPV204, HPV1, and HPV63. We detected several nucleotide substitutions and deletions within the LCR genomic regions of Mu-PVs and identified two genetic variants of HPV204 and HPV63 and five genetic variants of HPV1. PMID:28426749

High prevalence of human papillomavirus infection in American Indian women of the Northern Plains

PubMed Central

Bell, Maria C.; Schmidt-Grimminger, Delf; Patrick, Sarah; Ryschon, Tim; Linz, Laurie; Chauhan, Subhash C.

2008-01-01

Objectives Cervical cancer is the leading gynecological malignancy worldwide, and the incidence of this disease is very high in American Indian women. Infection with the Human Papillomavirus (HPV) is responsible for more than 95% of cervical squamous carcinomas. Therefore, the main objective of this study was to analyze oncogenic HPV infections in American Indian women residing in the Northern Plains. Methods Cervical samples were collected from 287 women attending a Northern Plains American Indian reservation outpatient clinic. DNA was extracted from the cervical samples and HPV specific DNA were amplified by polymerase chain reaction (PCR) using the L1 consensus primer sets. The PCR products were hybridized with the Roche HPV Line Blot assay for HPV genotyping to detect 27 different low and high-risk HPV genotypes. The chi-square test was performed for statistical analysis of the HPV infection and cytology diagnosis data. Results Of the total 287 patients, 61 women (21.25%) tested positive for HPV infection. Among all HPV-positive women, 41 (67.2%) were infected with high-risk HPV types. Of the HPV infected women, 41% presented with multiple HPV genotypes. Additionally, of the women infected with oncogenic HPV types, 20 (48.7%) were infected with HPV 16 and 18 and the remaining 21 (51.3%) were infected with other oncogenic types (i.e., HPV59, 39, 73). Women infected with oncogenic HPV types had significantly higher (p=0.001) abnormal Papanicolaou smear tests (Pap test) compared to women who were either HPV negative or positive for non-oncogenic HPV types. The incidence of HPV infection was inversely correlated (p<0.05) with the age of the patients, but there was no correlation (p=0.33) with seasonal variation. Conclusions In this study, we observed a high prevalence of HPV infection in American Indian women residing on Northern Plains Reservations. In addition, a significant proportion of the oncogenic HPV infections were other than HPV16 and 18. PMID:17659767

Vaccinating Girls and Boys with Different Human Papillomavirus Vaccines: Can It Optimise Population-Level Effectiveness?

PubMed Central

Drolet, Mélanie; Boily, Marie-Claude; Van de Velde, Nicolas; Franco, Eduardo L.; Brisson, Marc

2013-01-01

Background Decision-makers may consider vaccinating girls and boys with different HPV vaccines to benefit from their respective strengths; the quadrivalent (HPV4) prevents anogenital warts (AGW) whilst the bivalent (HPV2) may confer greater cross-protection. We compared, to a girls-only vaccination program with HPV4, the impact of vaccinating: 1) both genders with HPV4, and 2) boys with HPV4 and girls with HPV2. Methods We used an individual-based transmission-dynamic model of heterosexual HPV infection and diseases. Our base-case scenario assumed lifelong efficacy of 100% against vaccine types, and 46,29,8,18,6% and 77,43,79,8,0% efficacy against HPV-31,-33,-45,-52,-58 for HPV4 and HPV2, respectively. Results Assuming 70% vaccination coverage and lifelong cross-protection, vaccinating boys has little additional benefit on AGW prevention, irrespective of the vaccine used for girls. Furthermore, using HPV4 for boys and HPV2 for girls produces greater incremental reductions in SCC incidence than using HPV4 for both genders (12 vs 7 percentage points). At 50% vaccination coverage, vaccinating boys produces incremental reductions in AGW of 17 percentage points if both genders are vaccinated with HPV4, but increases female incidence by 16 percentage points if girls are switched to HPV2 (heterosexual male incidence is incrementally reduced by 24 percentage points in both scenarios). Higher incremental reductions in SCC incidence are predicted when vaccinating boys with HPV4 and girls with HPV2 versus vaccinating both genders with HPV4 (16 vs 12 percentage points). Results are sensitive to vaccination coverage and the relative duration of protection of the vaccines. Conclusion Vaccinating girls with HPV2 and boys with HPV4 can optimize SCC prevention if HPV2 has higher/longer cross-protection, but can increase AGW incidence if vaccination coverage is low among boys. PMID:23840589

Improved survival with HPV among African Americans with oropharyngeal cancer.

PubMed

Worsham, Maria J; Stephen, Josena K; Chen, Kang Mei; Mahan, Meredith; Schweitzer, Vanessa; Havard, Shaleta; Divine, George

2013-05-01

A major limitation of studies reporting a lower prevalence rate of human papilloma virus (HPV) in African American patients with oropharyngeal squamous cell cancer (OPSCC) than Caucasian Americans, with corresponding worse outcomes, was adequate representation of HPV-positive African American patients. This study examined survival outcomes in HPV-positive and HPV-negative African Americans with OPSCC. The study cohort of 121 patients with primary OPSCC had 42% African Americans. Variables of interest included age, race, gender, HPV status, stage, marital status, smoking, treatment, and date of diagnosis. Caucasian Americans are more likely to be HPV positive (OR = 3.28; P = 0.035), as are younger age (age < 50 OR = 7.14; P = 0.023 compared with age > 65) or being married (OR = 3.44; P = 0.016). HPV positivity and being unmarried were associated with being late stage (OR = 3.10; P = 0.047 and OR = 3.23; P = 0.038, respectively). HPV-negative patients had 2.7 times the risk of death as HPV-positive patients (P = 0.004). Overall, the HPV-race groups differed (log-rank P < 0.001), with significantly worse survival for HPV-negative African Americans versus (i) HPV-positive African Americans (HR = 3.44; P = 0.0012); (ii) HPV-positive Caucasian Americans (HR = 3.11; P = < 0.049); and (iii) HPV-negative Caucasian Americans (HR = 2.21; P = 0.049). HPV has a substantial impact on overall survival in African American patients with OPSCC. Among African American patients with OPSCC, HPV-positive patients had better survival than HPV negative. HPV-negative African Americans also did worse than both HPV-positive Caucasian Americans and HPV-negative Caucasian Americans. This study adds to the mounting evidence of HPV as a racially linked sexual behavior life style risk factor impacting survival outcomes for both African American and Caucasian American patients with OPSCC. ©2013 AACR.

Vaccinating Girls and Boys with Different Human Papillomavirus Vaccines: Can It Optimise Population-Level Effectiveness?

PubMed

Drolet, Mélanie; Boily, Marie-Claude; Van de Velde, Nicolas; Franco, Eduardo L; Brisson, Marc

2013-01-01

Decision-makers may consider vaccinating girls and boys with different HPV vaccines to benefit from their respective strengths; the quadrivalent (HPV4) prevents anogenital warts (AGW) whilst the bivalent (HPV2) may confer greater cross-protection. We compared, to a girls-only vaccination program with HPV4, the impact of vaccinating: 1) both genders with HPV4, and 2) boys with HPV4 and girls with HPV2. We used an individual-based transmission-dynamic model of heterosexual HPV infection and diseases. Our base-case scenario assumed lifelong efficacy of 100% against vaccine types, and 46,29,8,18,6% and 77,43,79,8,0% efficacy against HPV-31,-33,-45,-52,-58 for HPV4 and HPV2, respectively. Assuming 70% vaccination coverage and lifelong cross-protection, vaccinating boys has little additional benefit on AGW prevention, irrespective of the vaccine used for girls. Furthermore, using HPV4 for boys and HPV2 for girls produces greater incremental reductions in SCC incidence than using HPV4 for both genders (12 vs 7 percentage points). At 50% vaccination coverage, vaccinating boys produces incremental reductions in AGW of 17 percentage points if both genders are vaccinated with HPV4, but increases female incidence by 16 percentage points if girls are switched to HPV2 (heterosexual male incidence is incrementally reduced by 24 percentage points in both scenarios). Higher incremental reductions in SCC incidence are predicted when vaccinating boys with HPV4 and girls with HPV2 versus vaccinating both genders with HPV4 (16 vs 12 percentage points). Results are sensitive to vaccination coverage and the relative duration of protection of the vaccines. Vaccinating girls with HPV2 and boys with HPV4 can optimize SCC prevention if HPV2 has higher/longer cross-protection, but can increase AGW incidence if vaccination coverage is low among boys.

[HPV immunization for the prevention of cervical cancer].

PubMed

Mougin, Christiane; Bourgault-Villada, Isabelle; Coursaget, Pierre

2009-12-01

Human Papillomaviruses (HPV) infect epithelial cells of the skin and mucosae. Mucosal high-risk HPV types (mainly HPV 16 and 18) are involved in the development of cervical cancer, one of the most common cancers in young women. HPV infection is usually asymptomatic and clears spontaneously, but 10 - 15 % of high-risk HPV infections are persistent and increase the risk of precancerous and cancerous lesions of the cervix. Two HPV vaccines have been licensed to provide protection against cervical cancer. To report the different aspects of HPV infection in order to improve the understanding of the particular problems of HPV vaccination and to review the most recent findings related to HPV vaccines, particularly regarding the protective efficacy of vaccines and the roles of adjuvants and immune response in protection. Articles were selected from the PubMed database (National Library of Medicine- National Institute of Health) with the following Keywords "HPV", "Prevention", "HPV vaccines", "Immune response", "Antibody". Abstracts of oral presentations from international meetings were also selected for the more recent findings. a critical analysis of the majority of papers published was undertaken and relevant information summarized. Virus-like particle production by expressing the major protein of the HPV capsid was carried out in the early 90's, leading to the recent development of two HPV vaccines. These vaccines are now licensed in many countries and have been demonstrated to be highly immunogenic. In subjects that are non-infected at the time of vaccination, HPV vaccines are highly effective in preventing persistent HPV 16 - 18 infections (90 %) and precursors lesions of cervical cancer associated with these two HPV types (close to 100 %). Clinical trials have also confirmed that HPV vaccines are well tolerated by recipients. The present paper is a detailed review published in French on HPV vaccines, their efficacy in the prevention of HPV infections and unresolved questions regarding the use of HPV vaccines. This report also includes biological and immunological information to improve the understanding of HPV vaccination.

A 400 KHz line rate 2048-pixel stitched SWIR linear array

NASA Astrophysics Data System (ADS)

Anchlia, Ankur; Vinella, Rosa M.; Gielen, Daphne; Wouters, Kristof; Vervenne, Vincent; Hooylaerts, Peter; Deroo, Pieter; Ruythooren, Wouter; De Gaspari, Danny; Das, Jo; Merken, Patrick

2016-05-01

Xenics has developed a family of stitched SWIR long linear arrays that operate up to 400 KHz of line rate. These arrays serve medical and industrial applications that require high line rates as well as space applications that require long linear arrays. The arrays are based on a modular ROIC design concept: modules of 512 pixels are stitched during fabrication to achieve 512, 1024 and 2048 pixel arrays. Each 512-pixel module has its own on-chip digital sequencer, analog readout chain and 4 output buffers. This modular concept enables a long array to run at a high line rates irrespective of the array length, which limits the line rate in a traditional linear array. The ROIC is flip-chipped with InGaAs detector arrays. The FPA has a pixel pitch of 12.5μm and has two pixel flavors: square (12.5μm) and rectangular (250μm). The frontend circuit is based on Capacitive Trans-impedance Amplifier (CTIA) to attain stable detector bias, and good linearity and signal integrity, especially at high speeds. The CTIA has an input auto-zero mechanism that allows to have low detector bias (<20mV). An on-chip Correlated Double Sample (CDS) facilitates removal of CTIA KTC and 1/f noise, and other offsets, achieving low noise performance. There are five gain modes in the FPA giving the full well range from 85Ke- to 40Me-. The measured input referred noise is 35e-rms in the highest gain mode. The FPA operates in Integrate While Read mode and, at a master clock rate of 60MHz and a minimum integration time of 1.4μs, achieves the highest line rate of 400 KHz. In this paper, design details and measurements results are presented in order to demonstrate the array performance.

HPV-Associated Oropharyngeal Cancer Rates by Race and Ethnicity

MedlinePlus

... and Ethnicity HPV-Associated Anal Cancer HPV-Associated Cervical Cancer HPV-Associated Oropharyngeal Cancers Rates by State HPV-Associated Cervical Cancer HPV-Associated Oropharyngeal Cancers Diagnosis by Age Trends by ...

High-risk HPV types and head and neck cancer.

PubMed

Michaud, Dominique S; Langevin, Scott M; Eliot, Melissa; Nelson, Heather H; Pawlita, Michael; McClean, Michael D; Kelsey, Karl T

2014-10-01

Although HPV16 has been strongly implicated in oropharyngeal carcinogenesis, the role of other high-risk HPV types in the etiology of head and neck cancer remains unclear. To date, few data exist addressing the nature of the association between antibodies to oncogenic proteins of non-HPV16 HPVs in relation to head and neck cancer. We examined the relationship between multiple HPV types (HPV6, 11, 16, 18, 31, 33, 45, 52, 58) and head and neck squamous cell carcinoma (HNSCC) in a large population-based case-control study (1069 cases and 1107 controls). Serological measures for HPV types included antibodies to L1, E6 and/or E7. In a secondary analysis, we excluded HPV16 seropositive subjects to examine independent associations with other high-risk HPVs. All analyses were adjusted for age, race, sex, education, smoking and alcohol consumption. Statistically significant associations were observed for HPV16, 18, 33 and 52 and risk of HNSCC after mutually adjusting for HPV types. Among HPV16 seronegative subjects, elevated risks of HNSCC were observed for HPV18 E6 (OR = 4.19, 95% CI = 1.26-14.0), HPV33 E6 (OR = 7.96, 95% CI = 1.56-40.5) and HPV52 E7 (OR = 3.40, 95% CI = 1.16-9.99). When examined by tumor type, associations with HPV18 and HPV33 remained statistically significant for oropharyngeal cancer, and HPV52 was associated with oral cancer. In addition, magnitude of associations for HNSCC increased markedly with increasing number of seropositive high-risk HPV infections. High-risk HPV types, other than HPV16, are likely to be involved in the etiology of HNSCC. © 2014 UICC.

Differences in incidence and co-occurrence of vaccine and nonvaccine human papillomavirus types in Finnish population before human papillomavirus mass vaccination suggest competitive advantage for HPV33.

PubMed

Merikukka, Marko; Kaasila, Marjo; Namujju, Proscovia B; Palmroth, Johanna; Kirnbauer, Reinhard; Paavonen, Jorma; Surcel, Heljä-Marja; Lehtinen, Matti

2011-03-01

To understand likelihood of type replacement after vaccination against the high-risk human papillomavirus (HPV) types, we evaluated competition of the seven most common genital HPV types in a population sample of unvaccinated, fertile-aged Finnish women. First trimester sera from two consecutive pregnancies were retrieved from 3,183 Finnish women (mean age, 23.1 years) of whom 42.3% had antibodies to at least one HPV type (6/11/16/18/31/33/45) at the baseline. Antibody positivity to more than one HPV types by the second pregnancy was common among the baseline HPV seropositives. However, compared to baseline HPV-seronegative women, significantly increased incidence rate ratios (IRRs), indicating an increased risk to seroconvert for another HPV type, were consistently noted only for HPV33 among baseline HPV16 or HPV18 antibody (ab)-positive women: HPV(16ab only) (→) (16&33ab) IRR 2.9 [95% confidence interval (CI) 1.6-5.4] and HPV(18ab only) (→) (18&33ab) IRR 2.5 (95% CI 1.1-6.0), irrespectively of the presence of antibodies to other HPV types at baseline: HPV(16ab) (→) (16&33ab) IRR 3.2 (95% CI 2.0-5.2) and HPV(18ab) (→) (18&33ab) IRR 3.6 (95% CI 2.1-5.9). Our findings suggest a possible competitive advantage for HPV33 over other genital HPV types in the unvaccinated population. HPV33 should be monitored for type replacement after HPV mass vaccination. Copyright © 2010 UICC.

Prevalence and type distribution of human papillomavirus (HPV) in Malaysian women with and without cervical cancer: an updated estimate.

PubMed

Tan, Shing Cheng; Ismail, Mohd Pazudin; Duski, Daniel Roza; Othman, Nor Hayati; Ankathil, Ravindran

2018-04-27

Information on the prevalence and type distribution of human papillomavirus (HPV) among Malaysian women is currently limited. The present study therefore aimed to provide an updated estimate on the prevalence and type distribution of HPV among Malaysian women with and without cervical cancer. Total DNA was isolated from the cervical cell specimens of 185 histopathologically confirmed cervical cancer patients and 209 cancer-free healthy females who were tested negative in a recent Pap test. Viral-specific DNA was subsequently amplified with biotinylated primers and hybridized to HPV type-specific probes via a proprietary "flow-through hybridization" process for determination of HPV genotype. It was demonstrated that 83.2% of the cervical cancer patients and none (0.0%) of the cancer-free females were positive for HPV infection. Among HPV-positive subjects, 14 different viral genotypes were observed, namely HPV16, 18, 31, 33, 35, 45, 52, 53, 58, 66/68, 73, 81, 82, and 84/26. A total of 91.6% of the HPV-positive subjects had single-type HPV infections and the remaining 8.4% were simultaneously infected by two HPV genotypes. The most common HPV infections found were HPV16 (35.7%), HPV18 (26.0%), HPV58 (9.1%), and HPV33 (7.1%) single-type infections, followed by HPV16 + HPV18 co-infections (5.2%). The study has successfully provided an updated estimate on the prevalence and type distribution of HPV among Malaysian women with and without cervical cancer. These findings could contribute valuable information for appraisal of the impact and cost-effectiveness of prophylactic HPV vaccines in the Malaysian population. © 2018 The Author(s).

Clinical Significance of an HPV DNA Chip Test with Emphasis on HPV-16 and/or HPV-18 Detection in Korean Gynecological Patients.

PubMed

Yeo, Min-Kyung; Lee, Ahwon; Hur, Soo Young; Park, Jong Sup

2016-07-01

Human papillomavirus (HPV) is a major risk factor for cervical cancer. We evaluated the clinical significance of the HPV DNA chip genotyping assay (MyHPV chip, Mygene Co.) compared with the Hybrid Capture 2 (HC2) chemiluminescent nucleic acid hybridization kit (Digene Corp.) in 867 patients. The concordance rate between the MyHPV chip and HC2 was 79.4% (kappa coefficient, κ = 0.55). The sensitivity and specificity of both HPV tests were very similar (approximately 85% and 50%, respectively). The addition of HPV result (either MyHPV chip or HC2) to cytology improved the sensitivity (95%, each) but reduced the specificity (approximately 30%, each) compared with the HPV test or cytology alone. Based on the MyHPV chip results, the odds ratio (OR) for ≥ high-grade squamous intraepithelial lesions (HSILs) was 9.9 in the HPV-16/18 (+) group and 3.7 in the non-16/18 high-risk (HR)-HPV (+) group. Based on the HC2 results, the OR for ≥ HSILs was 5.9 in the HR-HPV (+) group. When considering only patients with cytological diagnoses of "negative for intraepithelial lesion or malignancy" and "atypical squamous cell or atypical glandular cell," based on the MyHPV chip results, the ORs for ≥ HSILs were 6.8 and 11.7, respectively, in the HPV-16/18 (+) group. The sensitivity and specificity of the MyHPV chip test are similar to the HC2. Detecting HPV-16/18 with an HPV DNA chip test, which is commonly used in many Asian countries, is useful in assessing the risk of high-grade cervical lesions.

De-stigmatising human papillomavirus in the context of cervical cancer: a randomised controlled trial.

PubMed

Kwan, Tracy T C; Tam, Kar-Fai; Lee, Peter W H; Lo, Sue S T; Chan, Karen K L; Ngan, Hextan Y S

2010-12-01

To identify the components of a human papillomavirus (HPV) message contributing to reducing the stigma of HPV in cervical cancer. 294 ethnic Chinese women attending a community-based clinic in Hong Kong were randomly allocated to read one of three written HPV messages: Group 'lr+hrHPV': low-risk and high-risk HPVs facts, Group 'hrHPV': high-risk HPV facts only and Group 'ds+hrHPV': high-risk HPV facts and de-stigmatising components, namely being anti-stereotypical, motivational and low in complexity. Main outcome measures were high-risk HPV-related sexual stigma, knowledge, attitude towards message, and intention to be HPV-tested measured by self-administered questionnaires immediately before and after reading. Message allocation had a significant effect on sexual stigma (F = 5.219, p = 0.006). Participants who read message ds+hrHPV showed the least stigma, and were significantly less likely to believe that high-risk HPV infection implicated promiscuity, non-monogamy or that monogamy offered complete protection against high-risk HPV. The genital HPV-focused message was more stigmatising than cervical cancer-focused messages. Of all participants, 93% (237/254) and 97% (260/269) indicated a positive intention to be HPV-tested before and after reading, respectively. There were no between-group differences noted in terms of knowledge and intention to be HPV-tested before or after reading. Our findings show that an HPV message containing specific de-stigmatising components may reduce public stigma towards high-risk HPV. Also, focusing solely on high-risk HPV in the context of cervical cancer helps to avoid the stigmatising effect of genital warts from tainting perceptions about high-risk HPV infection. Copyright © 2010 John Wiley & Sons, Ltd.

Predictors of Adults' Knowledge and Awareness of HPV, HPV-Associated Cancers, and the HPV Vaccine: Implications for Health Education.

PubMed

McBride, Kimberly R; Singh, Shipra

2018-02-01

High human papillomavirus (HPV) prevalence and low HPV vaccine uptake are significant public health concerns. Disparities in HPV-associated cancers and HPV vaccine uptake rates suggest the need for additional research examining factors associated with vaccine acceptance. This study assessed HPV awareness and knowledge and identified sociodemographic characteristics associated with HPV knowledge at the population level. Data from adult men ( n = 1,197) and women ( n = 1,906) who participated in the National Cancer Institute's 2014 Health Information National Trends Survey were analyzed. Multivariable regression was used to identify predictors of four HPV knowledge categories: (1) general knowledge, (2) cervical cancer knowledge, (3) "other" cancer knowledge (i.e., anal, oral, penile), and (4) vaccine knowledge. Significant gender differences in awareness and knowledge of HPV and the HPV vaccine were revealed. Most participants (>70%) knew that HPV could cause cervical cancer, but fewer (14.9% to 31.5%) knew of the association between HPV and "other" cancers. Women were more likely to report that a health care provider recommended vaccination. Significant predictors of general HPV and HPV vaccine knowledge included gender, education, income, race, and other sociodemographic characteristics. Age and income predicted cervical cancer knowledge. Knowledge of "other" HPV-associated cancers was predicted by having a child under 18 years in the household and relationship status. HPV knowledge appears to be socially patterned. Low HPV knowledge among men and some racial minorities suggests a need for further intervention. Health education should emphasize risks of noncervical HPV-associated cancers. Patient-provider communication that includes education, counseling, and clear recommendations favoring vaccination may improve uptake.

Human papillomavirus genotype distribution and cervical squamous intraepithelial lesions among high-risk women with and without HIV-1 infection in Burkina Faso

PubMed Central

Didelot-Rousseau, M-N; Nagot, N; Costes-Martineau, V; Vallès, X; Ouedraogo, A; Konate, I; Weiss, H A; Van de Perre, P; Mayaud, P; Segondy, M

2006-01-01

Human papillomavirus (HPV) infection and cervical squamous intraepithelial lesions (SILs) were studied in 379 high-risk women. Human papillomavirus DNA was detected in 238 of 360 (66.1%) of the beta-globin-positive cervical samples, and 467 HPV isolates belonging to 35 types were identified. Multiple (2–7 types) HPV infections were observed in 52.9% of HPV-infected women. The most prevalent HPV types were HPV-52 (14.7%), HPV-35 (9.4%), HPV-58 (9.4%), HPV-51 (8.6%), HPV-16 (7.8%), HPV-31 (7.5%), HPV-53 (6.7%), and HPV-18 (6.4%). Human immunodeficiency virus type 1 (HIV-1) seroprevalence was 36.0%. Human papillomavirus prevalence was significantly higher in HIV-1-infected women (87 vs 54%, prevalence ratio (PR)=1.61, 95% confidence interval (CI): 1.4–1.8). High-risk HPV types (71 vs 40%, PR=1.79, 95% CI: 1.5–2.2), in particular HPV-16+18 (22 vs 9%, PR=2.35, 95% CI: 1.4–4.0), and multiple HPV infections (56 vs 23%, PR=2.45, 95% CI: 1.8–3.3) were more prevalent in HIV-1-infected women. High-grade SIL (HSIL) was identified in 3.8% of the women. Human immunodeficiency virus type 1 infection was strongly associated with presence of HSIL (adjusted odds ratio=17.0; 95% CI 2.2–134.1, P=0.007) after controlling for high-risk HPV infection and other risk factors for HSIL. Nine of 14 (63%) HSIL cases were associated with HPV-16 or HPV-18 infection, and might have been prevented by an effective HPV-16/18 vaccine. PMID:16832413

HPV outcomes in an access to care laryngeal cancer cohort

PubMed Central

Stephen, Josena K.; Chen, Kang Mei; Shah, Veena; Havard, Shaleta; Lu, Mei; Schweitzer, Vanessa G.; Gardner, Glendon; Worsham, Maria J.

2013-01-01

Objective Human papillomavirus (HPV), particularly HPV16, is a causative agent for 25% of head and neck squamous cell cancer, including laryngeal squamous cell cancer (LSCC). HPV positive (HPV+ve) patients, particularly oropharyngeal SCC, have improved prognosis. For LSCC, this remains to be established. The goal was to determine stage and survival outcomes in LSCC in the context of HPV infection. Study Design Historical cohort study. Setting Primary care academic health system. Subjects and Methods In 79 primary LSCC, HPV was determined using real-time quantitative PCR. Chi-square or Fisher’s exact test was used to test association of HPV+ve with 21 risk factors including race, stage, gender, age, smoking, alcohol, treatment, and health insurance. Kaplan-Meier and log rank test were used to study the association of HPV and LSCC survival outcome. Results HPV16 was detected in 27% LSCC. There was a trend towards higher HPV prevalence in Caucasian American (CA, 33%) vs African American (AA, 16%) (p=0.058). HPV was significantly associated with gender (p=0.016) and insurance type (p=0.001). HPV+ve LSCC had a slightly longer survival than HPV-negative (HPV−ve) patients, but the differences were not significant. There was no association with HPV and other risk factors including stage (early vs late). Conclusion We found high prevalence of HPV in males and lower prevalence of HPV infection in AA compared to CA. A slightly better survival for HPV+ve LSCC versus HPV−ve was noted but was not significant. Larger multi ethnic LSCC cohorts are needed to more clearly delineate HPV related survival across ethnicities. PMID:22267491

A systematic review and meta-analysis on the attribution of human papillomavirus (HPV) in neuroendocrine cancers of the cervix.

PubMed

Castle, Philip E; Pierz, Amanda; Stoler, Mark H

2018-02-01

There remains uncertainty about the role of human papillomavirus (HPV) infection in causing small-cell neuroendocrine carcinoma (SCNC) and large-cell neuroendocrine carcinoma (LCNC) of the cervix. To clarify the role of HPV in the development of SCNC and LCNC, we conducted a systematic review and meta-analyses. PubMed and Embase were searched to initially identify 143 articles published on or before June 1, 2017. Studies were limited to methods that tested for HPV in the cancer tissue directly to minimize misattribution. Thirty-two studies with 403 SCNC and 9 studies of 45 LCNC were included in the analysis. For SCNC, 85% (95% confidence interval [95%CI]=71%-94%) were HPV positive, 78% (95%CI=64%-90%) were HPV16 and/or HPV18 positive, 51% (95%CI=39%-64%) were singly HPV18 positive, and 10% (95%CI=4%-19%) were singly HPV16 positive. In a subset of 5 SCNC studies (75 cases), 93% were positive for p16 INK4a by immunohistochemistry and 100% were HPV positive. For LCNC, 88% (95%CI=72%-99%) were HPV positive, 86% (95%CI=70%-98%) were positive for HPV16 or HPV18, 30% were singly HPV18 positive (95%CI=4%-60%), and 29% (95%CI=2%-64%) were singly HPV16 positive. In conclusion, most SCNC and LCNC are caused by HPV, primarily HPV18 and HPV16. Therefore, most if not all SCNC and LCNC will be prevented by currently available prophylactic HPV vaccines. Copyright © 2017 Elsevier Inc. All rights reserved.

Human papillomavirus infections in vulvar precancerous lesions and cancer.

PubMed

Costa, S; Syrjänen, S; Vendra, C; Chang, F; Guida, G; Hippeläinen, M; Terzano, P; Tervahauta, A; Yliskoski, M; Syrjänen, K

1995-04-01

To elucidate some of the recently arisen issues related to the bimodal disease pattern of vulvar intraepithelial lesions (VIN) and vulvar cancer, a series of 27 consecutive women with vulvar symptoms was analyzed for human papillomavirus (HPV) involvement by colposcopy, light microscopy and in situ hybridization (ISH) for HPV types 6, 11, 16, 18, 31, 33 and 42. Altogether, HPV DNA was discovered in 13/27 (48.1%) of the lesions by ISH; the rest were HPV DNA negative for the seven HPV types tested. HPV DNA was present in both of two exophytic lesions (HPV 6 in condyloma and HPV 16 in verrucous cancer). Of the flat lesions, 7/13 (53.8%) were HPV DNA positive. HPV 6 was confined to low grade lesions (HPV/non-VIN and VIN 1), whereas HPV 11 was found in a case of VIN 3 as well. Of the invasive carcinomas, three of four were HPV DNA positive (2 HPV 16 and 1 HPV 31). Dystrophic changes were detected in three of four invasive carcinomas and in all three HPV 16-positive lesions. Dystrophic changes were absent in 9 of 14 (64.3%) of HPV DNA-negative lesions. Fifty percent (7/14) of vulvar warty lesions (without concomitant VIN) were found in women younger than 60. Three of four invasive carcinomas occurred in women older than 60. This small series provided additional evidence of HPV involvement in the pathogenesis of VIN lesions, and the findings support the hypothesis of a multifactorial etiology in vulvar carcinogenesis in which HPV, dystrophic changes and chronic inflammatory disease play a synergistic role.

Human papillomavirus infections in women seeking cervical Papanicolaou cytology of Durango, Mexico: prevalence and genotypes

PubMed Central

Sánchez-Anguiano, Luis Francisco; Alvarado-Esquivel, Cosme; Reyes-Romero, Miguel Arturo; Carrera-Rodríguez, Margarita

2006-01-01

Background HPV infection in women from developing countries is an important public health problem. Therefore, we sought to determine the prevalences of HPV infection and HPV genotypes in a female population of Durango City, Mexico. Also to determine whether any socio-demographic characteristic from the women associated with HPV infection exists. Methods Four hundred and ninety eight women seeking cervical Papanicolaou examination in three public Health Centers were examined for HPV infection. All women were tested for HPV DNA PCR by using HPV universal primers. In addition, all positive HPV DNA PCR samples were further analyzed for genotyping of HPV genotype 16, 18 and 33. Socio-demographic characteristics from each participant were also obtained. Results Twenty-four out of four hundred and ninety-eight (4.8%) women were found infected by HPV. HPV genotype 16 was found in 18 out of the 24 (75%) infected women. Two of them were also coinfected by HPV genotype 18 (8.3%). In the rest 6 PCR positive women, genotyping for HPV genotypes 16, 18 and 33 were negative. Conclusion The prevalence of HPV in women of Durango City is low; however, most infected women have high risk HPV genotype. The women who were studied showed low frequency of risk factors for HPV infection and this may explain the low prevalence of HPV infection. The high frequency of high risk HPV genotypes observed might explain the high rate of mortality for cervical cancer in our region. PMID:16504014

Human papillomavirus infections in women seeking cervical Papanicolaou cytology of Durango, Mexico: prevalence and genotypes.

PubMed

Sánchez-Anguiano, Luis Francisco; Alvarado-Esquivel, Cosme; Reyes-Romero, Miguel Arturo; Carrera-Rodríguez, Margarita

2006-02-20

HPV infection in women from developing countries is an important public health problem. Therefore, we sought to determine the prevalences of HPV infection and HPV genotypes in a female population of Durango City, Mexico. Also to determine whether any socio-demographic characteristic from the women associated with HPV infection exists. Four hundred and ninety eight women seeking cervical Papanicolaou examination in three public Health Centers were examined for HPV infection. All women were tested for HPV DNA PCR by using HPV universal primers. In addition, all positive HPV DNA PCR samples were further analyzed for genotyping of HPV genotype 16, 18 and 33. Socio-demographic characteristics from each participant were also obtained. Twenty-four out of four hundred and ninety-eight (4.8%) women were found infected by HPV. HPV genotype 16 was found in 18 out of the 24 (75%) infected women. Two of them were also coinfected by HPV genotype 18 (8.3%). In the rest 6 PCR positive women, genotyping for HPV genotypes 16, 18 and 33 were negative. The prevalence of HPV in women of Durango City is low; however, most infected women have high risk HPV genotype. The women who were studied showed low frequency of risk factors for HPV infection and this may explain the low prevalence of HPV infection. The high frequency of high risk HPV genotypes observed might explain the high rate of mortality for cervical cancer in our region.

PATTERNS OF PERSISTENT GENITAL HUMAN PAPILLOMAVIRUS INFECTION AMONG WOMEN WORLDWIDE: A LITERATURE REVIEW AND META-ANALYSIS

PubMed Central

Rositch, Anne F.; Koshiol, Jill; Hudgens, Michael; Razzaghi, Hilda; Backes, Danielle M.; Pimenta, Jeanne M.; Franco, Eduardo L.; Poole, Charles; Smith, Jennifer S.

2013-01-01

Persistent high-risk human papillomavirus (HR-HPV) infection is the strongest risk factor for high-grade cervical precancer. We performed a systematic review and meta-analysis of HPV persistence patterns worldwide. Medline and ISI Web of Science were searched through January 1, 2010 for articles estimating HPV persistence or duration of detection. Descriptive and meta-regression techniques were used to summarize variability and the influence of study definitions and characteristics on duration and persistence of cervical HPV infections in women. Among 86 studies providing data on over 100,000 women, 73% defined persistence as HPV positivity at a minimum of two time points. Persistence varied notably across studies and was largely mediated by study region and HPV type, with HPV-16, 31, 33 and 52 being most persistent. Weighted median duration of any-HPV detection was 9.8 months. HR-HPV (9.3 months) persisted longer than low-risk HPV (8.4 months), and HPV-16 (12.4 months) persisted longer than HPV-18 (9.8 months). Among populations of HPV positive women with normal cytology, the median duration of any-HPV detection was 11.5 and HR-HPV detection was10.9 months. In conclusion, we estimated that approximately half of HPV infections persist past 6–12 months. Repeat HPV testing at 12 month intervals could identify women at increased risk of high-grade cervical precancer due to persistent HPV infections. PMID:22961444

Line region hypomethylation is associated with lifestyle and differs by human papillomavirus status in head and neck squamous cell carcinomas.

PubMed

Furniss, C Sloane; Marsit, Carmen J; Houseman, E Andres; Eddy, Karen; Kelsey, Karl T

2008-04-01

Genomic hypomethylation is a hallmark of essentially all cancers, but the degree of this hypomethylation differs among individual tumors. Little work has explored what leads to these differences and or asked whether they are clinically meaningful. In this study of head and neck squamous cell carcinoma, we assessed hypomethylation in tumors using a semiquantitative fragment analysis approach to determine the relative methylation status of the line retroviral element LRE1 (Line-1.2). Because this is an established marker of genomic methylation status, we examined the relationship between the relative methylation, patient demographics, and other risk factors for head and neck squamous cell carcinoma. We determined relative methylation status for 303 patients, 193 of which had complete data for all variables of interest. Using a generalized linear model, we found that patient body mass index was significantly positively associated with tumor LRE1 methylation level. Smoking duration, particularly in tumors lacking human papillomavirus (HPV) DNA, was significantly negatively associated with relative methylation level. Having previously assessed relative methylation in blood-derived DNA, we compared tumor with the blood DNA methylation level and observed these to be independent. Finally, the lower LRE1 methylation in patients whose tumors were HPV DNA negative was associated with poorer patient survival (hazard ratio, 1.6; 95% confidence interval, 1.0-2.6). These findings suggest that HPV-associated tumors differ molecularly from those arising after heavy tobacco use and that this epigenetic alteration may affect survival in HPV-negative patients already exhibiting a more aggressive disease.

Unusual and unique distribution of anal high-risk human papillomavirus (HR-HPV) among men who have sex with men living in the Central African Republic

PubMed Central

Camengo, Serge Police; Veyer, David; Matta, Mathieu; Robin, Leman; Longo, Jean De Dieu; Grésenguet, Gérard; Péré, Hélène; Meye, Jean-François; Belec, Laurent

2018-01-01

Background High-risk (HR) human papillomavirus (HPV) infection remains a great concern in relation to African men who have sex with men (MSM), especially those infected with HIV. The prevalence of HR-HPV and associated risk factors was estimated in a cross-sectional observational study covering MSM living in Bangui, Central African Republic. Methods MSM receiving care at the Centre National de Référence des Infections Sexuellement Transmissibles et de la Thérapie Antirétrovirale, Bangui, were included. HIV serostatus and socio-demographic and behavioral characteristics were collected. HPV DNA was detected and genotyped on anal swabs using Anyplex™ II HPV28 test (Seegene, South Korea), and HSV DNA by in-house real-time PCR. Logistic regression analyses were used to determine risk factors associated with HPV outcomes. Results 42 MSM (mean age, 23.2 years; range, 14–39) including 69.1% HIV-1-positive and 30.9% HIV-negative were prospectively enrolled. The prevalence of anal HPV was 69.1%, including 82.7% of HR-HPV which were multiple in 52.0%. The most prevalent genotypes were HPV-35, HPV-58, HPV-59 and HPV-31. While, HPV-16 and HPV-18 were present in a minority of samples. Multiple HR-HPV infection was more frequent in HIV-positive MSM (41.4%) with 2.7 genotypes per anal samples than in HIV-negative (7.7%) with 1.5 genotypes per anal samples. HPV types included in the prophylactic Gardasil-9® vaccine were detected in 68.9% of specimens and HPV-58 was the most frequently detected. MSM infected by HPV-16 and HPV-18 were all infected by HIV-1. Few anal swabs (11.9%) contained HSV-2 DNA without relationship with HPV detection. Condomless receptive anal intercourse was the main risk factor to being infected with any type of HPV and condomless insertive anal intercourse was significantly less associated with HPV contamination than receptive anal intercourse (Odd ratio = 0.02). Conclusion MSM in Bangui are at-risk of HIV and HR-HPV anal infections. The unusual distribution of HPV-35 as predominant HPV suggests possible geographic specificities in the molecular epidemiology of HR-HPV in sub-Saharan Africa. Scaling up prevention strategies against HPV infection and related cancers adapted for MSM in Africa should be prioritized. Innovative interventions should be conceived for the MSM population living in Bangui. PMID:29795661

Oral and cervical human papillomavirus infection among female sex workers in Japan.

PubMed

Matsushita, Kaori; Sasagawa, Toshiyuki; Miyashita, Michiko; Ishizaki, Azumi; Morishita, Atsushi; Hosaka, Norimitsu; Saikawa, Kunikazu; Hoshina, Shinji; Bi, Xiuqiong; Ichimura, Hiroshi

2011-01-01

It has been reported recently that oral human papillomavirus (HPV) infection is associated with oropharyngeal squamous cell carcinomas. The aim of this study was to determine the prevalence of HPV infection and HPV types in the oral cavity and cervix of female sex workers in Japan. Oral and cervical swabs were taken from 196 female sex workers who visited a clinic for regular medical checkups in 2007, and genomic DNA was extracted from those specimens. The HPV L1 gene was amplified by polymerase chain reaction (PCR) using original and modified GP5(+)/6(+) primers, and genotyping was performed using the Kurabo GeneSquare Microarray or by sequencing cloned PCR products. HPV DNA was detected in the oral cavity of 12 (6.1%) women, with HPV-56 being the most common type (7/12). Likewise, HPV DNA was detected in the cervix of 103 (52.6%) women, with HPV-52 (30/103, 29.1%), followed by HPV-16 (24.3%) and HPV-56 (18.4%), being the most common. Of the 12 women with oral HPV infection, only two were infected with the concordant HPV genotype in the cervix. These findings suggest that oral HPV infection occurs independently of cervical HPV infection in this population, and that oral HPV infection may play a role in HPV transmission in Japan.

Human papillomavirus in normal conjunctival tissue and in conjunctival papilloma: types and frequencies in a large series

PubMed Central

Sjö, Nicolai Christian; von Buchwald, Christian; Cassonnet, Patricia; Norrild, Bodil; Prause, Jan Ulrik; Vinding, Troels; Heegaard, Steffen

2007-01-01

Aim To examine conjunctival papilloma and normal conjunctival tissue for the presence of human papillomavirus (HPV). Methods Archival paraffin wax‐embedded tissue from 165 conjunctival papillomas and from 20 histological normal conjunctival biopsy specimens was analysed for the presence of HPV by PCR. Specimens considered HPV positive using consensus primers, but with a negative or uncertain PCR result using type‐specific HPV probes, were analysed with DNA sequencing. Results HPV was present in 86 of 106 (81%) β‐globin‐positive papillomas. HPV type 6 was positive in 80 cases, HPV type 11 was identified in 5 cases and HPV type 45 was present in a single papilloma. All the 20 normal conjunctival biopsy specimens were β‐globin positive and HPV negative. Conclusion There is a strong association between HPV and conjunctival papilloma. The study presents the largest material of conjunctival papilloma investigated for HPV and the first investigation of HPV in normal conjunctival tissue. HPV types 6 and 11 are the most common HPV types in conjunctival papilloma. This also is the first report of HPV type 45 in conjunctival papilloma. PMID:17166894

Human papillomavirus type 18 chimeras containing the L2/L1 capsid genes from evolutionarily diverse papillomavirus types generate infectious virus

PubMed Central

Bowser, Brian S.; Chen, Horng-Shen; Conway, Michael J.; Christensen, Neil D.; Meyers, Craig

2011-01-01

Papillomaviruses (PVs) comprise a large family of viruses infecting nearly all vertebrate species, with more than 100 human PVs identified. Our previous studies showed that a mutant chimera HPV18/16 genome, consisting of the upper regulatory region and early ORFs of HPV18 and the late ORFs of HPV16, was capable of producing infectious virus in organotypic raft cultures. We were interested in determining whether the ability of this chimeric genome to produce infectious virus was the result of HPV18 and HPV16 being similarly oncogenic, anogenital types and whether more disparate PV types could also interact functionally. To test this we created a series of HPV18 chimeric genomes where the ORFs for the HPV18 capsid genes were replaced with the capsid genes of HPV45, HPV39, HPV33, HPV31, HPV11, HPV6b, HPV1a, CRPV, and BPV1. All chimeras were able to produce infectious chimeric viral particles, although with lower infectivity than wild-type HPV18. Steps in the viral life cycle and characteristics of the viral particles were examined to identify potential causes for the decrease in infectivity. PMID:21762735

HPV and HPV vaccine information among a national sample of college and university websites.

PubMed

Fontenot, Holly B; Fantasia, Heidi Collins; Sutherland, Melissa A; Lee-St John, Terrence

2016-04-01

To describe the availability of human papillomavirus (HPV) and HPV vaccine information accessible to college students via official college and university websites. A review and analysis of HPV and HPV vaccination information abstracted from a national sample (n = 214) of college/university websites. Three abstractors systematically evaluated quality and quantity of vaccination, sexual health, and HPV disease information from health service webpages. The majority of colleges/universities had designated student health service webpages (n = 181). Of these, 86% provided information on vaccinations, but less than 50% mentioned HPV or the HPV vaccine specifically and only 32% provided any HPV educational information. Colleges/university webpages that provide sexual health and or general vaccination information had higher odds of providing information on HPV and HPV vaccination. Nurse practitioners who care for college-aged persons need to be cognizant of the many ways they can promote HPV vaccination. Providing accurate information about resources available at student health centers is a way to promote health on campus; the findings from this study indicate that HPV and HPV vaccine information may be lacking on many college/university websites. ©2015 American Association of Nurse Practitioners.

Three novel papillomaviruses (HPV109, HPV112 and HPV114) and their presence in cutaneous and mucosal samples.

PubMed

Ekström, Johanna; Forslund, Ola; Dillner, Joakim

2010-02-20

To expand our knowledge of the genomic diversity of human papillomaviruses (HPVs), we searched for new HPVs in squamous cell carcinomas of the skin (SCC) and seemingly HPV-negative, otherwise typically HPV-associated lesions. We describe the characterization of three novel HPV types. HPV109 was isolated from an SCC, HPV112 from a condyloma and HPV114 from a low-grade cervical lesion. Pairwise alignment of the L1 sequences classified HPV114 to genus alpha species 3, whereas HPV112 defined a new species in the genus gamma. HPV109 had uncertain classification because of a low and about equal similarity in the L1 gene (between 60% and 65%) to different genera. Type-specific real-time PCRs of cervical samples, a majority from women with low grade atypical cytology, (n=2856) and various cutaneous samples (n=538), found HPV114 in 1.7% (48/2856) of the genital samples, whereas both HPV109 and 112 were rare viruses found at high viral loads only in their index samples. Copyright 2009 Elsevier Inc. All rights reserved.

Comparative humoral and cellular immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18–45 years: Follow-up through Month 48 in a Phase III randomized study

PubMed Central

Einstein, Mark H; Levin, Myron J; Chatterjee, Archana; Chakhtoura, Nahida; Takacs, Peter; Catteau, Grégory; Dessy, Francis J; Moris, Philippe; Lin, Lan; Struyf, Frank; Dubin, Gary

2014-01-01

We previously reported higher anti-HPV-16 and -18 immune responses induced by HPV-16/18 vaccine compared with HPV-6/11/16/18 vaccine at Month 7 (one month after completion of full vaccination series) in women aged 18–45 y in an observer-blind study NCT00423046; the differences of immune response magnitudes were maintained up to Month 24. Here we report follow-up data through Month 48. At Month 48, in according-to-protocol cohort for immunogenicity (seronegative and DNA-negative for HPV type analyzed at baseline), geometric mean titers of serum neutralizing antibodies were 2.0- to 5.2-fold higher (HPV-16) and 8.6- to 12.8-fold higher (HPV-18) in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. The majority of women in both vaccine groups remained seropositive for HPV-16. The same trend was observed for HPV-18 in HPV-16/18 vaccine group; however, seropositivity rates in HPV-6/11/16/18 vaccine group decreased considerably, particularly in the older age groups. In the total vaccinated cohort (regardless of baseline serological and HPV-DNA status), anti-HPV-16 and -18 neutralizing antibody levels induced by HPV-16/18 vaccine were higher than those induced by HPV-6/11/16/18 vaccine. CD4+ T-cell response for HPV-16 and HPV-18 was higher in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. Memory B-cell responses appeared similar between vaccine groups. Both vaccines were generally well tolerated. Overall, the higher immune response observed with the HPV-16/18 vaccine was maintained up to Month 48. A head-to-head study incorporating clinical endpoints would be required to confirm whether the observed differences in immune response between the vaccines influence the duration of protection they provided. PMID:25483700

An Examination of HPV16 Natural Immunity in Men Who Have Sex with Men (MSM) in the HPV in Men (HIM) Study.

PubMed

Beachler, Daniel C; Pinto, Ligia A; Kemp, Troy J; Nyitray, Alan G; Hildesheim, Allan; Viscidi, Raphael; Schussler, John; Kreimer, Aimée R; Giuliano, Anna R

2018-04-01

Background: Evidence suggests that natural antibodies developed after HPV16 infection may protect some women but not men against subsequent HPV16 reacquisition. Less is known whether antibodies developed following HPV16 infection are protective among men who have sex with men (MSM). Methods: Four hundred seventy-five MSM from the Human Papillomavirus Infection in Men (HIM) study were tested for serum antibodies to HPV16 L1 using enzyme-linked immunosorbent assays, and for anal and genital HPV16 DNA using PCR consensus primer system (PGMY 09/11). Adjusted Cox regression was used to evaluate whether baseline HPV16 seropositivity impacts subsequent genital or anal HPV16 DNA. Results: The risk of subsequent genital HPV16 [aHR = 1.05, 95% confidence interval (CI) = 0.66-1.68] and anal HPV16 infections among MSM (aHR = 2.34, 95% CI = 0.92-5.98) was similar or nonsignificantly higher in HPV16-seropositive than HPV16-seronegative MSM. The risk of genital HPV16 was also similar between HPV16-seronegative and HPV16-seropositive MSM in the highest tertile of HPV16 antibody levels and when restricting to those with new sex partners during follow-up ( P > 0.20). Among the 118 MSM who were HPV16 seropositive, 90% remained HPV16 seropositive up to 4 years later. When tested together, MSM with the highest antibody titers (top tertile) had similar levels to females (mean = 130.3 vs. 134.5 EU/mL, P = 0.84). Conclusions: Despite years of HPV16 seropositivity persistence and antibody titers comparable with females, this study suggested no evidence of HPV16 natural antibodies protecting against subsequent genital or anal HPV16 infection in MSM. Impact: This could help partially explain the high incidence of genital and anal HPV16 infection and related anal cancer seen in middle-aged and older MSM. Cancer Epidemiol Biomarkers Prev; 27(4); 496-502. ©2018 AACR . ©2018 American Association for Cancer Research.

Comparative humoral and cellular immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18-45 years: follow-up through Month 48 in a Phase III randomized study.

PubMed

Einstein, Mark H; Levin, Myron J; Chatterjee, Archana; Chakhtoura, Nahida; Takacs, Peter; Catteau, Grégory; Dessy, Francis J; Moris, Philippe; Lin, Lan; Struyf, Frank; Dubin, Gary

2014-01-01

We previously reported higher anti-HPV-16 and -18 immune responses induced by HPV-16/18 vaccine compared with HPV-6/11/16/18 vaccine at Month 7 (one month after completion of full vaccination series) in women aged 18-45 y in an observer-blind study NCT00423046; the differences of immune response magnitudes were maintained up to Month 24. Here we report follow-up data through Month 48. At Month 48, in according-to-protocol cohort for immunogenicity (seronegative and DNA-negative for HPV type analyzed at baseline), geometric mean titers of serum neutralizing antibodies were 2.0- to 5.2-fold higher (HPV-16) and 8.6- to 12.8-fold higher (HPV-18) in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. The majority of women in both vaccine groups remained seropositive for HPV-16. The same trend was observed for HPV-18 in HPV-16/18 vaccine group; however, seropositivity rates in HPV-6/11/16/18 vaccine group decreased considerably, particularly in the older age groups. In the total vaccinated cohort (regardless of baseline serological and HPV-DNA status), anti-HPV-16 and -18 neutralizing antibody levels induced by HPV-16/18 vaccine were higher than those induced by HPV-6/11/16/18 vaccine. CD4+ T-cell response for HPV-16 and HPV-18 was higher in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. Memory B-cell responses appeared similar between vaccine groups. Both vaccines were generally well tolerated. Overall, the higher immune response observed with the HPV-16/18 vaccine was maintained up to Month 48. A head-to-head study incorporating clinical endpoints would be required to confirm whether the observed differences in immune response between the vaccines influence the duration of protection they provided.

Population-Level Effects of Human Papillomavirus Vaccination Programs on Infections with Nonvaccine Genotypes

PubMed Central

Soldan, Kate; Lehtinen, Matti; Beddows, Simon; Brisson, Marc; Brotherton, Julia M.L.; Chow, Eric P.F.; Cummings, Teresa; Drolet, Mélanie; Fairley, Christopher K.; Garland, Suzanne M.; Kahn, Jessica A.; Kavanagh, Kimberley; Markowitz, Lauri; Pollock, Kevin G.; Söderlund-Strand, Anna; Sonnenberg, Pam; Tabrizi, Sepehr N.; Tanton, Clare; Unger, Elizabeth; Thomas, Sara L.

2016-01-01

We analyzed human papillomavirus (HPV) prevalences during prevaccination and postvaccination periods to consider possible changes in nonvaccine HPV genotypes after introduction of vaccines that confer protection against 2 high-risk types, HPV16 and HPV18. Our meta-analysis included 9 studies with data for 13,886 girls and women ≤19 years of age and 23,340 women 20–24 years of age. We found evidence of cross-protection for HPV31 among the younger age group after vaccine introduction but little evidence for reductions of HPV33 and HPV45. For the group this same age group, we also found slight increases in 2 nonvaccine high-risk HPV types (HPV39 and HPV52) and in 2 possible high-risk types (HPV53 and HPV73). However, results between age groups and vaccines used were inconsistent, and the increases had possible alternative explanations; consequently, these data provided no clear evidence for type replacement. Continued monitoring of these HPV genotypes is important. PMID:27648688

Efficiency of MY09/11 consensus PCR in the detection of multiple HPV infections.

PubMed

Şahiner, Fatih; Kubar, Ayhan; Gümral, Ramazan; Ardıç, Medine; Yiğit, Nuri; Şener, Kenan; Dede, Murat; Yapar, Mehmet

2014-09-01

Human papillomavirus (HPV) DNA testing has become an important component of cervical cancer screening programs. In this study, we aimed to evaluate the efficiency of MY09/11 consensus polymerase chain reaction (PCR) for the detection of multiple HPV infections. For this purpose, MY09/11 PCR was compared to an original TaqMan-based type-specific real-time PCR assay, which can detect 20 different HPV types. Of the 654 samples, 34.1% (223/654) were HPV DNA positive according to at least one method. The relative sensitivities of MY09/11 PCR and type-specific PCR were 80.7% (180/223) and 97.8% (218/223), respectively. In all, 352 different HPV isolates (66 low-risk and 286 high-risk or probable high-risk types) were identified in 218 samples, but 5 samples, which were positive by consensus PCR only, could not be genotyped. The distribution of the 286 high-risk or probable high-risk HPVs were as follows: 24.5% HPV-16, 8.4% HPV-52, 7.7% HPV-51, 6.3% HPV-39, 6.3% HPV-82, 5.6% HPV-35, 5.6% HPV-58, 5.6% HPV-66, 5.2% HPV-18, 5.2% HPV-68, and 19.6% the other 8 types. A single HPV type was detected in 57.3% (125/218) of the genotyped samples, and multiple HPV types were found in the remaining 42.7% (93/218). The false-negative rates of MY09/11 PCR were found to be 17.4% in single infections, 23.3% in multiple infections, and 34.6% in multiple infections that contained 3 or more HPV types, with the condition that the low-risk types HPV-6 and HPV-11 be considered as a monotype. These data suggest that broad-range PCR assays may lead to significant data loss and that type-specific PCR assays can provide accurate and reliable results during cervical cancer screening. Copyright © 2014 Elsevier Inc. All rights reserved.

Prevalence and genotype distribution of human papillomavirus infection of the cervix in Spain: the CLEOPATRE study.

PubMed

Castellsagué, Xavier; Iftner, Thomas; Roura, Esther; Vidart, José Antonio; Kjaer, Susanne K; Bosch, F Xavier; Muñoz, Nubia; Palacios, Santiago; San Martin Rodriguez, Maria; Serradell, Laurence; Torcel-Pagnon, Laurence; Cortes, Javier

2012-06-01

Human papillomavirus (HPV) infection is a necessary cause of cervical cancer. The aim of this study was to estimate the prevalence of cervical HPV infection and HPV type-specific distribution among women attending cervical cancer screening in Spain during 2007 and 2008. Women aged 18-65 years were recruited according to an age-stratified sampling method. Liquid-based cervical samples were collected and analyzed for cytology, HPV detection, and genotyping. HPV genotyping was determined using the INNO-LiPA HPV Genotyping Extra Reverse Hybridization Line Probe Assay. Prevalence estimates were age-standardized using 2001 Spanish census data. The present study included 3,261 women. Age-standardized HC2-based HPV prevalence was 14.3% (95% CI, 13.1-15.5) among women aged 18-65 years, and 28.8% (26.6-31.1) among women aged 18-25 years. High-risk HPV types were detected in 12.2% (95% CI, 11.1-13.4) of HPV-tested women, representing 84.0% of HPV-positive samples. Multiple infections were present in 4.1% (95% CI, 3.4-4.8) of HPV-tested women (25.0% of HPV-positive samples). The most common high-risk HPV-types among HPV-tested women were 16 (2.9%), 52 (1.8%), 51 (1.6%), 31 (1.3%), and 66 (1.2%). HPV-type 16 was present in 16.9% of HPV-positive samples. One or more of the HPV vaccine types 6/11/16/18 were detected in 3.8% of HPV-tested women (22.1% of HPV-positive samples). Though not a true population-based survey, this study provides valuable baseline data for future assessment of the impact of current HPV vaccination programs in Spain. The high prevalence of HPV infection among young women may reflect recent changes in sexual behavior. Copyright © 2012 Wiley Periodicals, Inc.

Assessment of human papilloma virus infection in adult laryngeal papilloma using a screening test.

PubMed

Makiyama, Kiyoshi; Hirai, Ryoji; Matsuzaki, Hiroumi; Ikeda, Minoru

2013-03-01

Human papilloma virus (HPV) infection is involved in both juvenile and adult laryngeal papilloma. We wished to determine which types of adult laryngeal papilloma were clinically related to HPV infection. We hypothesized that multiple-site and recurrent papillomas would have a strong relationship to HPV and conducted the present study to test this hypothesis. Thirteen male patients with adult laryngeal papilloma who underwent resection of papilloma between August 2006 and September 2009 were studied. We examined the relationships between whether the tumor was solitary or multiple, presence or absence of recurrence after surgery, and HPV infection. High-risk HPV types (HPV-DNA types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) and low-risk HPV types (6, 11, 42, 43, and 44) were tested by a liquid-phase hybridization method. In addition, HPV typing was performed for patients positive for low-risk HPV types. Twenty patients with laryngeal carcinoma or laryngeal leukoplakia were enrolled as the control group. In the laryngeal papilloma group, all patients tested were negative for high-risk HPV and 69.2% were positive for low-risk HPV. Typing performed for seven of the patients who tested positive for low-risk HPV showed that one patient was positive for HPV-11, whereas the remaining six patients were positive for HPV-6. All patients with recurrent laryngeal papillomatosis (RLP) were positive for low-risk HPV. All patients who were positive for low-risk HPV had RLP. Tumor samples from repeat operations were positive for low-risk HPV in all patients tested. HPV was not detected in the control group. The relationship between RLP and low-risk HPV was strong, with all cases that were positive for low-risk HPV showing recurrence. Tumor tissue resected at the time of repeat surgery was positive for low-risk HPV in all cases tested. Copyright © 2013 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

Distribution of Genital Wart Human Papillomavirus Genotypes in China: A Multi-Center Study

PubMed Central

Chang, Lihong; Ci, Puwa; Shi, Jufang; Zhai, Kan; Feng, Xiaoli; Colombara, Danny; Wang, Wei; Qiao, Youlin; Chen, Wen; Wu, Yuping

2017-01-01

Although it is understood that low-risk human papillomavirus (HPV) genotypes are associated with genital warts, there have been very few published studies reporting the genotype-specific prevalence of HPV among Chinese population. The aim of the study was to assess the prevalence of HPV genotypes in genital warts across China, and thus to evaluate the potential benefit of a quadrivalent HPV vaccine in this population. The tissue samples of a total of 1,005 genital warts cases were collected from seven geographical regions of China. HPV genotypes were analyzed using the general primer PCR and sequence-based typing method. Prevalence differences between sexes, geographical regions and age groups were assessed. The overall prevalence of HPV DNA in genital warts patients was 88.7% (891/1,005). Low-risk genotypes predominated, with a prevalence of 78.1% (785/1,005). The most prevalent genotypes were HPV-6 (41.3%), HPV-11 (37.6%) and HPV-16 (10.4%). Among HPV positive patients, single infections were more frequent (866/891, 97.2%) than co-infections (25/891, 2.8%). Both the overall prevalence of HPV DNA and that of HPV-6/-11/-16 (positive for any of the three types) decreased with age (P-trend = 0.010 and P-trend = 0.025, respectively). The prevalence of HPV-6/-11 (positive for either HPV type) and HPV-16 varied by geographic region (P = 0.003 and P ≤ 0.001, respectively). The prevalence of HPV-16 in female patients between urban and rural areas showed a marginally significant difference (P = 0.05). In sum, the results provide strong evidence that, in China, the most prevalent HPV genotypes in genital warts are HPV-6, HPV-11 and HPV-16. This indicates that a quadrivalent HPV vaccine may decrease the incidence of genital warts in the future. PMID:23861100

Comparing Immunohistologic and Demographic Variables of Head and Neck Squamous Cell Carcinoma

DTIC Science & Technology

2015-06-01

HPV 16 and 18 which have a well-established association with cervical cancers . However, HPV 16 accounts for the majority ofHPV...These cancers are now subdivided into HPV associated ( HPV - SCC) and non- HPV associated squamous cell (SCC) carcinomas. HPV -SCG is a distinct entity... cell carcinomas. Laryngoscope 2009; 119(8): 1542-1549. 13. Venuti A, Paolini F. HPV detection methods in head and neck cancer . Head Neck

Perceptions of HPV and attitudes towards HPV vaccination amongst men who have sex with men: A qualitative analysis.

PubMed

Nadarzynski, Tom; Smith, Helen; Richardson, Daniel; Pollard, Alex; Llewellyn, Carrie

2017-05-01

Men who have sex with men (MSM) are at risk of genital warts and anal cancer due to human papillomavirus (HPV) infection. This study explores MSMs' perceptions of HPV and HPV vaccination prior to the introduction of this programme. Focus groups and one-to-one interviews with self-identified MSM were conducted between November 2014 and March 2015 in Brighton, UK. Participants were recruited from community-based lesbian-gay-bisexual-transgender (LGBT) venues and organizations. Discussions were recorded, transcribed verbatim, and analysed using framework analysis. Thirty-three men took part (median age 25 years, IQR: 21-27), most of whom (n = 25) did not know about HPV, anal cancer (31), or HPV vaccination (26). While genital warts and anal cancer were perceived as severe, men did not perceive themselves at risk of HPV. All MSM would accept the HPV vaccine if offered by a health care professional. The challenges of accessing sexual health services or openly discussing same-sex experiences with health care professionals were perceived as barriers to accessing HPV vaccination. Two participants were concerned that selective HPV vaccination could increase stigma and prejudice against MSM, comparable to the AIDS epidemic. Ten MSM were unsure about the effectiveness of HPV vaccination for sexually active men and were in favour of vaccinating all adolescent boys at school. Most MSM have poor knowledge about HPV and associated anal cancer. Despite the lack of concern about HPV, most MSM expressed willingness to receive HPV vaccination. There is a need for health education about the risks of HPV and HPV-related diseases so that MSM can appraise the benefits of being vaccinated. Concerns about HPV vaccine effectiveness in sexually active men and possible stigmatization need to be addressed to optimize HPV vaccine acceptability. Statement of contribution What is already known on this subject? Men who have sex with men (MSM) have poor knowledge about HPV and HPV-related diseases. Perceived risk of HPV and attitudes towards HPV vaccination are associated with HPV vaccine acceptability amongst MSM in the United States. There is a gap between acceptability and uptake of HPV vaccination amongst MSM. What does this study add? Due to concerns about compromised effectiveness of the HPV vaccine in sexually active men, most MSM would recommend vaccination of all adolescent boys. Restricted access to sexual health services and the inability to discuss same-sex experiences were perceived as barriers to HPV vaccination. While the HPV vaccine is acceptable amongst MSM, the motivation to be vaccinated and complete the three-dose series might be low. © 2017 The British Psychological Society.

Atypical Clinical Behavior of p16-Confirmed HPV-Related Oropharyngeal Squamous Cell Carcinoma Treated With Radical Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang Shaohui; Perez-Ordonez, Bayardo; Liu Feifei

Purpose: To report atypical clinical behavior observed in human papillomavirus (HPV)-related oropharyngeal carcinoma (OPC) treated with radiotherapy. Methods and Materials: A retrospective cohort study was conducted for all newly diagnosed OPC cases treated with radiotherapy on July 1, 2003 to April 30, 2009. HPV positivity was determined by p16 immunostaining in tumors. The incidence of additional malignancies and the pattern of distant metastases (DMs) were compared between the HPV-positive (HPV+) and HPV-negative (HPV-) cohorts. Results: HPV status was evaluated in 318 of 613 consecutive OPC cases (52%), showing 236 HPV+ and 82 HPV- patients. Compared with HPV-, HPV+ cases weremore » less likely to have additional malignancies (prior: 11% vs. 20%, p = 0.038; synchronous: 1% vs. 9%, p = 0.001; metachronous: 6% vs. 16%, p = 0.003). Whereas the majority (10 of 12) of HPV- additional head-and-neck (HN) mucosal malignancies were in the oral cavity, there was none (0 of 7) in the HPV+ cohort (p < 0.001). HPV+ synchronous HN second primaries (SPs) were in the supraglottis, post-cricoid, and nasopharynx; metachronous HN SPs were in the glottis, supraglottis, and ethmoid plus glottis/post-cricoid region. All SPs that could be tested were HPV+. There was no difference in DM rate (10% vs. 15%, p = 0.272), but HPV+ DMs were more likely to involve multiple organs (46% vs. 0%, p = 0.005) and unusual sites. Conclusions: This study reports atypical clinical behavior seen in HPV+ OPC, including multicentric lesions in HN mucosa and DM to multiple organs and unusual sites. The frequency of these events is low, but they may have clinical implications. The routine assessment of HPV status for all OPC is warranted.« less

Prevalence of Anal HPV Infection Among HIV-Positive Men Who Have Sex With Men in India.

PubMed

Hernandez, Alexandra L; Karthik, Rajiv; Sivasubramanian, Murugesan; Raghavendran, Anantharam; Gnanamony, Manu; Lensing, Shelly; Lee, Jeannette Y; Kannangai, Rajesh; Abraham, Priya; Mathai, Dilip; Palefsky, Joel M

2016-04-01

India has a large population of HIV-positive individuals, including men who have sex with men (MSM), and the incidence of human papillomavirus (HPV)-related cancers is high. In developed countries, HIV-positive MSM exhibit the highest prevalence of anal HPV infection and incidence of anal cancer. Little is known about anal HPV infection in HIV-positive Indian MSM. We evaluated 300 HIV-positive MSM from 2 cities in India. Men were tested for anal HPV infection using L1-HPV DNA polymerase chain reaction with probes specific for 29 types and a mixture of 10 additional types. CD4 level and plasma HIV viral load were measured. Participants completed an interviewer-administered questionnaire including a sexual history. The prevalence of anal HPV was 95% (95% confidence interval: 91% to 97%). The 3 most common types were HPV 35 (20%), HPV 16 (13%), and HPV 6/11 (13%). History of taking antiretroviral medications decreased risk of anal HPV 16 infection [relative risk (RR): 0.6 (0.4-1.0)]. Having an increased number of vaginal sex partners lowered risk of any anal HPV infection. Ever having receptive sex increased risk of any anal HPV [RR: 1.2 (1.1-1.4)] and anal HPV 16 [RR: 6.5 (1.8-107)]. Almost all Indian HIV-positive MSM had anal HPV infection. The prevalence of HPV 16 was lower and the prevalence of other oncogenic HPV types was higher than in similar populations in North America and Europe. Vaccine-based prevention strategies for HPV infection in India should consider potential differences in HPV type distribution among HIV-infected MSM when designing interventions.

Prevalence of anal HPV infection among HIV-positive men who have sex with men in India

PubMed Central

Hernandez, Alexandra L.; Karthik, Rajiv; Sivasubramanian, Murugesan; Raghavendran, Anantharam; Gnanamony, Manu; Lensing, Shelly; Lee, Jeannette Y.; Kannangai, Rajesh; Abraham, Priya; Mathai, Dilip; Palefsky, Joel M.

2016-01-01

Background India has a large population of HIV-positive individuals, including men who have sex with men (MSM) and the incidence of human papillomavirus (HPV)-related cancers is high. In developed countries, HIV-positive MSM exhibit the highest prevalence of anal HPV infection and incidence of anal cancer. Little is known about anal HPV infection in HIV-positive Indian MSM. Methods We evaluated 300 HIV-positive MSM from two cities in India. Men were tested for anal HPV infection using L1-HPV DNA PCR with probes specific for 29 types and a mixture of 10 additional types. CD4+ level and plasma HIV viral load were measured. Participants completed an interviewer-administered questionnaire including a sexual history. Results The prevalence of anal HPV was 95% (95% CI 91%-97%). The three most common types were HPV 35 (20%), HPV 16 (13%) and HPV 6/11 (13%). History of taking antiretroviral medications decreased risk of anal HPV 16 infection (RR: 0.6 (0.4-1.0). Having an increased number of vaginal sex partners lowered risk of any anal HPV infection. Ever having receptive sex increased risk of any anal HPV (RR: 1.2 (1.1-1.4) and anal HPV 16 (RR: 6.5 1.8-107). Conclusions Almost all Indian HIV-positive MSM had anal HPV infection. The prevalence of HPV 16 was lower and the prevalence of other oncogenic HPV types was higher than in similar populations in North America and Europe. Vaccine based prevention strategies for HPV infection in India should consider potential differences in HPV type distribution among HIV-infected MSM when designing interventions. PMID:26379067

Head and neck cancer stem cells: the effect of HPV--an in vitro and mouse study.

PubMed

Tang, Alice L; Owen, John H; Hauff, Samantha J; Park, Jung Je; Papagerakis, Silvana; Bradford, Carol R; Carey, Thomas E; Prince, Mark E

2013-08-01

To determine if the behavior of cancer stem cells (CSCs) is affected by human papillomavirus (HPV) status. An in vitro and in vivo analysis of HPV and CSCs. University laboratory. We isolated CSCs from HPV-positive and HPV-negative cell lines. Two HPV-negative cell lines underwent lentiviral transduction of E6/E7. Chemoresistence was determined using colony formation assays. Native HPV-positive and HPV E6/E7-transduced cells were compared for lung colonization after tail vein injection in NOD/SCID mice. The proportion of CSC is not significantly different in HPV-positive or HPV-negative head and neck squamous cell carcinoma (HNSCC) cell lines. The HNSCC CSCs are more resistant to cisplatin than the non-CSCs, but there were no significant differences between HPV-positive and HPV-negative cells. The HPV-negative cancer cells yielded low colony formation after cell sorting. After transduction with HPV E6/E7, increased colony formation was observed in both CSCs and non-CSCs. Results from tail vein injections yielded no differences in development of lung colonies between HPV E6/E7-transduced cells and nontransduced cells. Human papillomavirus status does not correlate with the proportion of CSCs present in HNSCC. The HPV-positive cells and those transduced with HPV E6/E7 have a greater clonogenicity than HPV-negative cells. The HNSCC CSCs are more resistant to cisplatin than non-CSCs. This suggests that common chemotherapeutic agents may shrink tumor bulk by eliminating non-CSCs, whereas CSCs have mechanisms that facilitate evasion of cell death. Human papillomavirus status does not affect CSC response to cisplatin therapy, suggesting that other factors explain the better outcomes for patients with HPV-positive cancer.

Genital HPV infection among heterosexual and homosexual male attendees of sexually transmitted diseases clinic in Beijing, China.

PubMed

Xin, H N; Li, H J; Li, Z; Li, X W; Li, M F; Zhang, H R; Feng, B X; Lun, W H; Yan, H W; Long, J; Gao, L

2017-10-01

Human papillomavirus (HPV) has been identified as etiologic agent of various cancers for both men and women. However, HPV vaccine has not been recommended for men in China by far. To provide more evidences to promote HPV vaccination among males at high-risk of infection, this study investigated genital HPV genotypes among male attendees of sexually transmitted disease (STD) clinic. Male attendees (⩾18 years old) were recruited from STD clinic of Beijing Ditan Hospital. Data on sociodemographic characteristics and self-reported sexual behaviors were collected based on questionnaire. Genital swab specimens were collected for HPV genotypes. Finally, a total of 198 eligible participants were included in the study. Nearly half of them were infected with at least one type of HPV. The prevalence of genital infection among participants with only heterosexual behaviors (50·91%, 56/110) was significantly higher than those with only homosexual behaviors (36·36%, 32/88) (P < 0·001). However, the distribution pattern of the most frequently observed HPV subtypes were found to be similar between these two subgroups. HPV31, HPV18, HPV16 and HPV58 were the most frequently identified high-risk types and HPV11, HPV6, HPV81 and HPV61 were the most frequently observed low-risk types. Our results, although need further verification by larger sample size, suggested that currently available HPV vaccines covered most prevalent HPV types observed in Chinese men. As HPV vaccine has been approved for application in females in China, molecular epidemiological studies and intervention studies among high-risk males should be promoted as well.

Molecular epidemiology and genotype distribution of Human Papillomavirus (HPV) among Arab women in the State of Qatar.

PubMed

Bansal, Devendra; Elmi, Asha A; Skariah, Sini; Haddad, Pascale; Abu-Raddad, Laith J; Al Hamadi, Aysha H; Mohamed-Nady, Nady; Affifi, Nahla M; Ghedira, Randa; Hassen, Elham; Al-Thani, Asma A J; Al-Ansari, Afaf A H M; Sultan, Ali A

2014-11-26

Human Papilloma Virus (HPV) infection is the major cause of cervical cancer worldwide. With limited data available on HPV prevalence in the Arab countries, this study aimed to identify the prevalence and genotypic distribution of HPV in the State of Qatar. 3008 cervical samples, exclusively of women with Arabic origin residing in Qatar were collected from the Women's Hospital and Primary Health Care Corporation in Doha, State of Qatar. HPV DNA detection was done using GP5+/6+ primers based real time-polymerase chain reaction (RT-PCR) assay followed by the usage of HPV type specific primers based RT- PCR reactions and Sanger sequencing for genotype identification. Similar prevalence rates of HPV infection was identified in both Qatari and non-Qatari women at 6.2% and 5.9% respectively. HPV prevalence rate of 5.8% and 18.4% was identified in women with normal cytology and in women with abnormal cytology respectively. HPV 81, 11 and 16, in decreasing order were the most commonly identified genotypes. HPV 81 was the most frequent low-risk genotype among women with both normal (74.0%) and abnormal (33.3%) cytology. HPV 16 (4.6%) was identified as the predominant high-risk HPV genotype among women with normal cytology and HPV 16, HPV 18, and HPV 56 (22.2% each) were the most common identified high-risk genotypes in women with abnormal cytology. The overall HPV prevalence in Arab women in Qatar was identified as 6.1% with an increased HPV prevalence seen in women with abnormal cytology results and no significant trends seen with age. In contrast to Western countries, we report a varied genotypic profile of HPV with a high prevalence of low-risk HPV genotype 81 among the Arab women residing in Qatar.

Human papillomavirus load in benign HPV-associated oral lesions from HIV/AIDS individuals.

PubMed

Camacho-Aguilar, S; Ramírez-Amador, V; Rosendo-Chalma, P; Guido-Jiménez, M; García-Carrancá, A; Anaya-Saavedra, G

2018-03-01

Although HPV emerged as a crucial carcinogenic and prognostic biomarker in head and neck cancer, and considering the increase in HPV-associated oral lesions (HPV-OLs) in HIV individuals, molecular information about HPV-OLs is scarce; thus, our aim was to determine viral loads in HPV-OLs from HIV/AIDS individuals. HIV/AIDS subjects with HPV-OL were included in this cross-sectional study. Following informed consent, biopsies were obtained. HPV detection and typing were carried out by PCR and sequencing (MY09/11, GP5+/6+). HPV-13 and HPV-32 loads were determined by a high-resolution melting assay. For statistical analysis, X 2 , Fisher's exact, and Mann-Whitney U tests were applied, using SPSS software (v.23). Twenty-nine HIV subjects (median age 38 years, 93% males) were included. Most were AIDS individuals (72.4%) under HAART (89.7%). Twenty-two (75.9%) participants had more than one HPV-OL (four with florid presentations), mostly multifocal epithelial hyperplasia (62%), being HPV-13 (26%) and HPV-32 (31%) the most frequent types. HPV load was higher in individuals with multiple HPV-OLs than in solitary lesions (4.9 vs. 3.2 Log 10 copies/ml, p = .090) and in HPV-32 + than in HPV-13 + (8.3 vs. 6.4 Log 10 copies/ml, p = .014). Multiple HPV-OLs showed high HPV loads, possibly indicating transcriptional activity of the virus; however, in the HIV setting, the individual and local immunological response could be the key process. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

Identification of human papillomavirus (HPV) subtype in oral cancer patients through microarray technology.

PubMed

Kim, Soung Min; Kwon, Ik Jae; Myoung, Hoon; Lee, Jong Ho; Lee, Suk Keun

2018-02-01

Human papilloma virus (HPV) is the main source of cervical cancer. Many recent studies have revealed the prevalence and prognosis of HPV associated with oropharyngeal squamous cell carcinoma, but fewer reports have evaluated HPV in oral squamous cell carcinoma (OSCC). The purpose of this study was to determine the prevalence and prognosis of HPV associated with OSCC according to HPV and tumor types. We used a DNA chip kit (MY-HPV chip kit ® , Mygene Co., Korea) to detect high-risk HPV subtypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 54, 56, 58) and low-risk subtypes (6, 11, 34, 40, 42, 43, 44) among 187 patients. The prevalence was determined by Chi-square and Fisher's exact tests, and the prognosis was calculated by the Kaplan-Meier method and the log-rank test. The overall prevalence of HPV in OSCC was 7.0% for all HPV positives and 4.3% for high-risk HPV positives. The prevalence of HPV was significantly higher in individuals under 65 years old and in those with tumors in the tongue and gum regions. The prognosis did not differ between the HPV-positive and -negative groups. Although the prevalence of HPV-positive cases in OSCC was low (7.0, 4.3%) and the prognosis did not depend on HPV positivity, HPV-associated OSCC should be considered in the evaluation and treatment of oral cancer patients. In addition, separating high- and low-risk groups based on the HPV status of other body parts might not be appropriate. The DNA microarray method can accurately detect known HPV subtypes simultaneously, but has limitations in detecting new subtypes. Vaccines can also be used to prevent HPV-associated OSCC in patients, so further studies on the prognosis and efficacy of vaccines should be undertaken.

Human papillomavirus outcomes in an access-to-care laryngeal cancer cohort.

PubMed

Stephen, Josena K; Chen, Kang Mei; Shah, Veena; Havard, Shaleta; Lu, Mei; Schweitzer, Vanessa P; Gardner, Glendon; Worsham, Maria J

2012-05-01

Human papillomavirus (HPV), particularly HPV16, is a causative agent for 25% of head and neck squamous cell cancer, including laryngeal squamous cell cancer (LSCC). HPV-positive (HPV+ve) patients, particularly those with oropharyngeal SCC, have improved prognosis. For LSCC patients, this remains to be established. The goal was to determine stage and survival outcomes in LSCC in the context of HPV infection. Historical cohort study. Primary care academic health system. In 79 patients with primary LSCC, HPV was determined using real-time quantitative polymerase chain reaction. χ(2) or Fisher exact test was used to test the association of HPV+ve with 21 risk factors including race, stage, gender, age, smoking, alcohol, treatment, and health insurance. Kaplan-Meier and log-rank tests were used to study the association of HPV and LSCC survival outcome. HPV16 was detected in 27% of LSCC patients. Caucasian American (CA) patients had higher HPV prevalence (33%) than did African American (AA) LSCC patients (16%; P = .058). HPV was significantly associated with gender (P = .016) and insurance type (P = .001). There were no differences in survival between HPV+ve and HPV-negative (HPV-ve) patients. There was no association with HPV and other risk factors including stage (early vs late). We found a high prevalence of HPV in men and a lower prevalence of HPV infection in AA compared with CA. Despite the strikingly better survival of patients with HPV+ve oropharyngeal tumors, even when adjusted for smoking, this correlation does not seem to hold true in the larynx. Larger multiethnic LSCC cohorts are needed to more clearly delineate HPV-related survival across ethnicities.

A systematic review of the prevalence and attribution of human papillomavirus types among cervical, vaginal, and vulvar precancers and cancers in the United States.

PubMed

Insinga, Ralph P; Liaw, Kai-Li; Johnson, Lisa G; Madeleine, Margaret M

2008-07-01

To describe prevalence and estimated attribution of human papillomavirus (HPV) types in U.S. cervical, vaginal, and vulvar precancers and cancers. U.S. studies reporting HPV typing for cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), and vaginal intraepithelial neoplasia (VaIN) and/or invasive cancers of those sites were gathered from the PubMed database (http://www.ncbi.nlm.nih.gov/sites/entrez/). Selected studies had PCR testing data for > or =10 cases for a disease endpoint. Analytic methods augmented prior reviews of cervical disease with an updated and expanded analysis (including vulvar and vaginal disease), new selection criteria for specimens, and adjustment for histologic type, where possible, among pooled cancer cases. In addition, for analyses of estimated attribution of HPV types, we incorporated accounting methods for lesions infected with multiple HPV types. Data from 22 U.S. studies meeting review eligibility criteria were tabulated. Following adjustment for the presence of multiple HPV types in a single specimen, the top two HPV types contributing to disease were CIN 1 (HPV 16/66; 15.3%), CIN 2/3 (HPV 16/31; 61.9%), cervical cancer (HPV 16/18; 79.2%), VIN 1 (HPV 6/11; 41.7%), VIN 3 (HPV 16/18; 84.0%), vulvar cancer (HPV 16/33; 55.5%), VaIN 3 (HPV 16/18; 65.1%), and vaginal cancer (HPV 16/18; 72.7%). The HPV type distribution and proportion of cases testing positive for any HPV type were observed to vary among U.S. cervical, vulvar, and vaginal neoplasias and by grade of disease. Adjustment for the presence of multitype HPV infections can have an important effect on the estimated attribution of HPV types to disease, particularly for types other than HPV 16.

Impact and Cost-effectiveness of 3 Doses of 9-Valent Human Papillomavirus (HPV) Vaccine Among US Females Previously Vaccinated With 4-Valent HPV Vaccine.

PubMed

Chesson, Harrell W; Laprise, Jean-François; Brisson, Marc; Markowitz, Lauri E

2016-06-01

We estimated the potential impact and cost-effectiveness of providing 3-doses of nonavalent human papillomavirus (HPV) vaccine (9vHPV) to females aged 13-18 years who had previously completed a series of quadrivalent HPV vaccine (4vHPV), a strategy we refer to as "additional 9vHPV vaccination." We used 2 distinct models: (1) the simplified model, which is among the most basic of the published dynamic HPV models, and (2) the US HPV-ADVISE model, a complex, stochastic, individual-based transmission-dynamic model. When assuming no 4vHPV cross-protection, the incremental cost per quality-adjusted life-year (QALY) gained by additional 9vHPV vaccination was $146 200 in the simplified model and $108 200 in the US HPV-ADVISE model ($191 800 when assuming 4vHPV cross-protection). In 1-way sensitivity analyses in the scenario of no 4vHPV cross-protection, the simplified model results ranged from $70 300 to $182 000, and the US HPV-ADVISE model results ranged from $97 600 to $118 900. The average cost per QALY gained by additional 9vHPV vaccination exceeded $100 000 in both models. However, the results varied considerably in sensitivity and uncertainty analyses. Additional 9vHPV vaccination is likely not as efficient as many other potential HPV vaccination strategies, such as increasing primary 9vHPV vaccine coverage. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Prevalence and Determinants of High-Risk Human Papillomavirus Infection in Male Genital Warts

PubMed Central

Park, Sung Jin; Seo, Juhyung; Ha, Seong-Heon

2014-01-01

Purpose To evaluate the prevalence and type distribution of high-risk human papillomavirus (HPV) infection in genital warts of Korean men, and for the first time, to describe the risk factors associated with high-risk HPV infection in male genital warts. Materials and Methods In a single private clinic, 150 consecutive male patients with histopathologic-confirmed genital warts who underwent HPV genotyping by use of polymerase chain reaction (PCR) were included in this study. We detected HPV DNA in male genital warts and evaluated HPV type distribution, especially high-risk HPV types, by use of PCR. The associations between HPV prevalence and various characteristics, such as age, circumcision status, type of genital warts diagnosis (new vs. recurrent), number of lesions, site of lesions, and gross morphology, were assessed by use of unconditional multiple logistic regression. Results High-risk HPV types were detected in 31 cases (23.5%), and of these, 27 cases (20.5%) contained both high-risk and low-risk HPV types. The most frequently detected high-risk HPV types were HPV16 (6.8%), HPV33 (4.5%), HPV18 (2.3%), and HPV68 (2.3%). In particular, the prevalence of infection with HPV16 and/or HPV18 was 8.3% (11 of 132). In the multivariate analysis, lesions located at sites including the base of the penis or the pubic area, papular or mixed genital warts, and lack of circumcision significantly increased the association with high-risk HPV infection in male genital warts. Conclusions The prevalence of high-risk HPV infection was substantial in male genital warts. The site and morphology of lesions and circumcision status were significantly associated with the prevalence of high-risk HPV infection. PMID:24648877

Prevalence and determinants of high-risk human papillomavirus infection in male genital warts.

PubMed

Park, Sung Jin; Seo, Juhyung; Ha, Seong-Heon; Jung, Gyung-Woo

2014-03-01

To evaluate the prevalence and type distribution of high-risk human papillomavirus (HPV) infection in genital warts of Korean men, and for the first time, to describe the risk factors associated with high-risk HPV infection in male genital warts. In a single private clinic, 150 consecutive male patients with histopathologic-confirmed genital warts who underwent HPV genotyping by use of polymerase chain reaction (PCR) were included in this study. We detected HPV DNA in male genital warts and evaluated HPV type distribution, especially high-risk HPV types, by use of PCR. The associations between HPV prevalence and various characteristics, such as age, circumcision status, type of genital warts diagnosis (new vs. recurrent), number of lesions, site of lesions, and gross morphology, were assessed by use of unconditional multiple logistic regression. High-risk HPV types were detected in 31 cases (23.5%), and of these, 27 cases (20.5%) contained both high-risk and low-risk HPV types. The most frequently detected high-risk HPV types were HPV16 (6.8%), HPV33 (4.5%), HPV18 (2.3%), and HPV68 (2.3%). In particular, the prevalence of infection with HPV16 and/or HPV18 was 8.3% (11 of 132). In the multivariate analysis, lesions located at sites including the base of the penis or the pubic area, papular or mixed genital warts, and lack of circumcision significantly increased the association with high-risk HPV infection in male genital warts. The prevalence of high-risk HPV infection was substantial in male genital warts. The site and morphology of lesions and circumcision status were significantly associated with the prevalence of high-risk HPV infection.

The Effect of History of Abnormal Pap Smear or Preceding HPV infection on the Humoral Immune Response to Quadrivalent Human Papilloma virus (qHPV) Vaccine in Women with Systemic Lupus Erythematosus.

PubMed

Dhar, J Patricia; Essenmacher, Lynnette; Dhar, Renee; Magee, Ardella; Ager, Joel; Sokol, Robert J

2018-04-30

To determine if natural human papillomavirus (HPV) infection would induce an anamnestic response to quadrivalent (qHPV) vaccine in women with Systemic Lupus Erythematosus (SLE). Thirty four women (19-50 years) with mild to moderate and minimally active or inactive SLE received standard qHPV vaccine. Neutralizing antibody titers to HPV 6, 11, 16 and18 were evaluated pre- and post- vaccine using HPV competitive Luminex Immunoassay. For each HPV type, logistic regressions were performed to explore the relationship between a positive titer at baseline with their final geometric mean titer and with the rise in titer. Fisher's Exact Test was used to assess the association of at least one positive HPV antibody test at baseline and history of abnormal pap. History of abnormal pap smear/cervical neoplasia occurred in 52.9%. Baseline anti HPV antibody titers: 21% = negative for all 4 HPV types, 79% = positive for ≥1 of the HPV types. Statistical analysis showed: those with a history of abnormal pap smear/cervical neoplasia were likely to have a positive anti-HPV antibody result pre-vaccine to ≥ 1 of the 4 types, p = 0.035 Fisher's Exact Test. In general, HPV exposed women showed higher post vaccine GMTs than HPV unexposed women with higher point estimates. However, when examining the rise in titers using logistic regression, there was no evidence of an anamnestic response. Prior HPV infection and cervical neoplasia in SLE are linked with no anamnestic response to HPV vaccine. This supports not checking HPV-antibodies pre-vaccine. Women with SLE should be vaccinated for HPV.

Burden of HPV-caused cancers in Denmark and the potential effect of HPV-vaccination.

PubMed

Skorstengaard, Malene; Thamsborg, Lise Holst; Lynge, Elsebeth

2017-10-13

Denmark is one of the countries where Human papillomavirus (HPV)-vaccination at present includes only girls. However, the burden of HPV-related cancer in men is increasing, which would argue for gender-neutral vaccination. The aim of this study was to examine the burden of HPV-caused cancers in women and men, and to evaluate the potential of HPV-vaccination in cancer control. Data were retrieved from the literature on population prevalence of high risk (HR) HPV, on HR HPV-prevalence and genotypes in HPV-related cancers, and on number of cytology samples in cervical screening. Data on annual biopsies and conisations were retrieved from the Danish National Health Service Register and the Danish National Patient Register. Incidences of HPV-related cancers in Denmark were extracted from NORDCAN. Number of HPV-caused cancers was calculated from number of HPV-related cancers and the proportion known to be caused by high-risk (HR) HPV. In cross-sectional surveys in Denmark, one fifth of women and almost one third of men were found to be positive for HR HPV. Per year, 548 HPV-caused cancer cases were diagnosed in women and 234 in men, and twice as many cancers in women as in men were preventable with HPV vaccination. However, including screening prevented cervical cancers, the burden of cancers caused by HPV-infection would be 1300-2000 in women as compared to 234 in men. Taking screening prevented cervical cancers into account, the cancer control potential of HPV-vaccination is considerably higher in women than in men. HPV-vaccination could reduce the burden of screening on women and on health care resources. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Two major pathways of penile carcinogenesis: HPV-induced penile cancers overexpress p16ink4a, HPV-negative cancers associated with dermatoses express p53, but lack p16ink4a overexpression.

PubMed

Mannweiler, Sebastian; Sygulla, Stephan; Winter, Elke; Regauer, Sigrid

2013-07-01

Penile squamous cell carcinomas (SCC) arise either through transforming infections with human papillomavirus (HPV) or independent of HPV, often in the background of lichen sclerosus (LS) and lichen planus (LP). Despite impact on therapy and prognosis, etiologic stratifications are missing in most histological diagnoses and publications about penile cancers/precursors. Classification of penile lesions into HPV-induced or HPV-negative via immunohistochemical demonstration of p16(ink4a) overexpression, a surrogate marker for transforming HPV-high-risk infections, and p53 expression in the absence of p16(ink4a) overexpression. Archival formalin-fixed material of 123 invasive penile cancers and 43 pre-invasive lesions was evaluated for the presence of LS, LP, 28 HPV genotypes, and expression of p53 and p16(ink4a). Seventy-two of 123 SCCs and 33 of 43 pre-invasive lesions showed p16(ink4a) overexpression independent of HPV-HR genotypes involved; 66 of 72 SCCs and 29 of 43 precursor lesions revealed a single HPV-high-risk-genotype (HPV-HR16 in 76% followed by HPV33, HPV31, HPV45, HPV18, HPV56); 5 of 72 SCCs and 4 of 43 precursor lesions revealed multiple HPV-HR-genotypes. One SCC revealed HPV-LR and HR-DNA. Fifty-one of 123 SCCs and 10 precursor lesions were p16(ink4a) negative, but showed nuclear p53 expression in tumor cells and basal keratinocytes. Forty-nine of 51 SCCs and 10 of 10 precursor lesions lacked HPV DNA. Two of 51 SCCs contained HPV18 and HPV45 DNA, respectively, but p16(ink4a) negativity classified them as non-HPV-induced. Twenty-seven of 51 SCCs showed peritumoral LS, 13 of 51 SCCs showed peritumoral LP, and 11 SCCs revealed no peritumoral tissue. Histologically, HPV-negative precursors showed hyperkeratotic, verrucous, atrophic, and basaloid differentiation. This was a retrospective study. p16(ink4a) overexpression identifies HPV-HR-induced penile carcinogenesis independent of HPV-HR genotype. p53 expression along with p16(ink4a) negativity identifies HPV-negative cancers. Correct etiologic classification of penile lesions during diagnostic work-up allows optimal therapy decisions. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

HPV vaccine awareness and the association of trust in cancer information from physicians among males.

PubMed

Cooper, Dexter L; Hernandez, Natalie D; Rollins, Latrice; Akintobi, Tabia Henry; McAllister, Calvin

2017-05-09

Black and Hispanic men are diagnosed with more HPV-related cancers and at later stages compared to other racial/ethnic groups. Physician communication with men about HPV vaccination may be beneficial to increasing HPV vaccinations and decreasing HPV transmission. The purpose of this study was to examine HPV and HPV vaccine awareness among men by race, and the association between trust in cancer information from physicians and ever hearing about HPV and the HPV vaccine. U.S. adult males (age 18+) were identified from the 2014 Health Information National Trends Survey (HINTS) (n=1203). Binomial logistic regression models assessed the influences of race/ethnicity and trust of cancer information from physicians on men having heard of HPV and the HPV vaccination. Approximately 50% of the sample had never heard of HPV and 53% had never heard of the vaccine. Black men were less likely to know that HPV is sexually transmitted compared to White and Hispanic men (p<0.001). Hispanic and Black men were less likely to have heard about the HPV vaccine when compared to White men (p<0.001). Additionally, Hispanic men were less likely to trust a doctor about cancer information compared to White and Black men (p<0.001). Findings highlight the lack of awareness about HPV among men. Furthermore, statistically significant racial/ethnic differences were found in HPV vaccine knowledge and trust in receiving cancer information from physicians. Future interventions should include community-based approaches and improved physicians' HPV-related communication to increase knowledge and uptake of the HPV vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.

HPV infection and P16 expression in oral and oropharyngeal cancer in Kazakhstan.

PubMed

Adilbay, Dauren; Adilbayev, Galim; Kidirbayeva, Gulzhan; Shipilova, Viktoria; Sadyk, Zhanat; Koyanbekova, Gulsum; Sokolenko, Ekaterina; Klozar, Jan

2018-01-01

Human papillomavirus (HPV) is an important etiologic factor in different cancers of anogenital region and also in a fraction of head and neck cancers (HNC) particularly oropharyngeal tumors. The HPV16 genotype associated with the majority of HPV-related head and neck carcinomas. Th incidence of oropharyngeal cancer is increasing in many countries, and the rate of HPV positive tumors is about 70% in Europe and North America. Little known about the prevalence of HPV in HNC in Central Asia. It's a prospective analysis of patients with verified oral or oropharyngeal cancer. Sociodemographic and clinical data obtained on admission to treatment. The diagnosis of HPV positivity assessed by both the P16 expression on immunohistochemistry(IHC) and polymerase chain reaction (PCR)with HPV DNA detection and HR HPV type determination. Seventy six patients with oral and oropharyngeal cancer tested for HPV. Forteen cases were positive for HPV by PCR and 15 cases by P16 IHC. Of the 35 oropharyngeal tumors, nine were HPV DNA and p16 IHC positive, giving the rate of 25.7%. Of the 41 oral tumors, five were HPV DNA and six p16 IHC positive, giving the rate of 12.2%. It is the first study mapping prevalence of HPV positivity in oral and oropharyngeal cancer in the Central Asian region. The rate of HPV positivity was higher in oropharyngeal than in oral cancer, the nonsmokers were significantly more frequent in the HPV positive group and HPV 16 was the most frequent type. However, the HPV positivity rates are lower than referred in the western world.

Changes in HPV Knowledge Among College Women from 2008 to 2015.

PubMed

Thompson, Erika L; Vamos, Cheryl A; Griner, Stacey B; Daley, Ellen M

2018-04-01

The human papillomavirus (HPV) can cause anogenital cancers and genital warts; however, it can be prevented through the HPV vaccine, which has been available since 2006. While this vaccine is targeted toward 11-to-12-year-olds, 18-to-26-year-old young adult women are eligible for "catch-up" vaccination. Knowledge of HPV may impact HPV vaccine uptake among this population. The purpose of this study was to assess changes in HPV knowledge and HPV vaccine information sources among young adult college women over a 7-year period. Two independent samples (N = 223 for 2008; N = 323 for 2015) completed a 23-item knowledge scale and survey regarding HPV. Adjusted logistic regression models compared the odds of correctly answering each knowledge item between each time period. The study found that HPV knowledge increased significantly over time (p < 0.01). The participants in 2015 were more likely than the 2008 participants to accurately report that a condom can decrease the chance of HPV transmission; there is a vaccine for women that prevents certain types of HPV; HPV can cause genital warts; HPV can be passed to a newborn at birth; and even if you do not see a wart, you can transmit HPV. Recent participants were also more likely to correctly report only women can get HPV as false. While improvements in HPV knowledge were found over time, misperceptions regarding outcomes associated with HPV persist. In order to promote HPV vaccination among this population, health literacy skills, in addition to knowledge, should be improved.

Chimeric L2-Based Virus-Like Particle (VLP) Vaccines Targeting Cutaneous Human Papillomaviruses (HPV)

PubMed Central

Huber, Bettina; Schellenbacher, Christina; Shafti-Keramat, Saeed; Jindra, Christoph; Christensen, Neil

2017-01-01

Common cutaneous human papillomavirus (HPV) types induce skin warts, whereas species beta HPV are implicated, together with UV-radiation, in the development of non-melanoma skin cancer (NMSC) in immunosuppressed patients. Licensed HPV vaccines contain virus-like particles (VLP) self-assembled from L1 major capsid proteins that provide type-restricted protection against mucosal HPV infections causing cervical and other ano-genital and oro-pharyngeal carcinomas and warts (condylomas), but do not target heterologous HPV. Experimental papillomavirus vaccines have been designed based on L2 minor capsid proteins that contain type-common neutralization epitopes, to broaden protection to heterologous mucosal and cutaneous HPV types. Repetitive display of the HPV16 L2 cross-neutralization epitope RG1 (amino acids (aa) 17–36) on the surface of HPV16 L1 VLP has greatly enhanced immunogenicity of the L2 peptide. To more directly target cutaneous HPV, L1 fusion proteins were designed that incorporate the RG1 homolog of beta HPV17, the beta HPV5 L2 peptide aa53-72, or the common cutaneous HPV4 RG1 homolog, inserted into DE surface loops of HPV1, 5, 16 or 18 L1 VLP scaffolds. Baculovirus expressed chimeric proteins self-assembled into VLP and VLP-raised NZW rabbit immune sera were evaluated by ELISA and L1- and L2-based pseudovirion (PsV) neutralizing assays, including 12 novel beta PsV types. Chimeric VLP displaying the HPV17 RG1 epitope, but not the HPV5L2 aa53-72 epitope, induced cross-neutralizing humoral immune responses to beta HPV. In vivo cross-protection was evaluated by passive serum transfer in a murine PsV challenge model. Immune sera to HPV16L1-17RG1 VLP (cross-) protected against beta HPV5/20/24/38/96/16 (but not type 76), while antisera to HPV5L1-17RG1 VLP cross-protected against HPV20/24/96 only, and sera to HPV1L1-4RG1 VLP cross-protected against HPV4 challenge. In conclusion, RG1-based VLP are promising next generation vaccine candidates to target cutaneous HPV infections. PMID:28056100

E2 Proteins from High- and Low-Risk Human Papillomavirus Types Differ in Their Ability To Bind p53 and Induce Apoptotic Cell Death

PubMed Central

Parish, Joanna L.; Kowalczyk, Anna; Chen, Hsin-Tien; Roeder, Geraldine E.; Sessions, Richard; Buckle, Malcolm; Gaston, Kevin

2006-01-01

The E2 proteins from oncogenic (high-risk) human papillomaviruses (HPVs) can induce apoptotic cell death in both HPV-transformed and non-HPV-transformed cells. Here we show that the E2 proteins from HPV type 6 (HPV6) and HPV11, two nononcogenic (low-risk) HPV types, fail to induce apoptosis. Unlike the high-risk HPV16 E2 protein, these low-risk E2 proteins fail to bind p53 and fail to induce p53-dependent transcription activation. Interestingly, neither the ability of p53 to activate transcription nor the ability of p53 to bind DNA, are required for HPV16 E2-induced apoptosis in non-HPV-transformed cells. However, mutations that reduce the binding of the HPV16 E2 protein to p53 inhibit E2-induced apoptosis in non-HPV-transformed cells. In contrast, the interaction between HPV16 E2 and p53 is not required for this E2 protein to induce apoptosis in HPV-transformed cells. Thus, our data suggest that this high-risk HPV E2 protein induces apoptosis via two pathways. One pathway involves the binding of E2 to p53 and can operate in both HPV-transformed and non-HPV-transformed cells. The second pathway requires the binding of E2 to the viral genome and can only operate in HPV-transformed cells. PMID:16611918

Detection and genotyping of human papilloma virus in cervical cancer specimens from Saudi patients.

PubMed

Al-Badawi, Ismail A; Al-Suwaine, Abdulrahman; Al-Aker, Murad; Asaad, Lina; Alaidan, Alwaleed; Tulbah, Asma; Fe Bohol, Marie; Munkarah, Adnan R

2011-07-01

To determine the rates and types of human papilloma virus (HPV) infection in cervical cancer specimens from Saudi patients. One hundred specimens were randomly selected and retrieved from the achieved samples stored in the pathology department accessioned under the diagnosis of cervical cancer and carcinoma in situ between the years 1997 and 2007. Human papilloma virus in the clinical samples was detected using polymerase chain reaction amplification methods. Two primer systems are commonly used: the MY09-MY11 primers and the GP5+-GP6+ that amplify a wide range of HPV genotypes. Human papilloma virus isolates were genotyped using DNA sequencing and reverse line blot hybridization assay to identify the high-risk HPV genotypes. Ninety cases fulfilled the diagnostic criteria and were analyzed. The rate of HPV genotype detection among cervical cancer samples was 95.5%. The most common HPV genotype detected by both methods was HPV-16 (63.4%), followed by HPV-18 (11.1%), HPV-45 (4.5%), HPV-33 (3.3%), and HPV-31, HPV-52, HPV-53, HPV-58, HPV-59, and HPV-66 with 2.2% prevalence rate each. Prevalence of HPV genotypes among patients with cervical cancer in Saudi Arabia is comparable to the international rates. The use of the reverse line blot hybridization assay genotyping method could be useful for classifying oncogenic HPV-positive women. It is relatively inexpensive and reliable and can be performed in routine practice or epidemiological study compared with the available standard commercial kits.

hnRNP L controls HPV16 RNA polyadenylation and splicing in an Akt kinase-dependent manner

PubMed Central

Kajitani, Naoko; Glahder, Jacob; Wu, Chengjun; Yu, Haoran; Nilsson, Kersti

2017-01-01

Abstract Inhibition of the Akt kinase activates HPV16 late gene expression by reducing HPV16 early polyadenylation and by activating HPV16 late L1 mRNA splicing. We identified ‘hot spots’ for RNA binding proteins at the early polyA signal and at splice sites on HPV16 late mRNAs. We observed that hnRNP L was associated with sequences at all HPV16 late splice sites and at the early polyA signal. Akt kinase inhibition resulted in hnRNP L dephosphorylation and reduced association of hnRNP L with HPV16 mRNAs. This was accompanied by an increased binding of U2AF65 and Sam68 to HPV16 mRNAs. Furthermore, siRNA knock-down of hnRNP L or Akt induced HPV16 gene expression. Treatment of HPV16 immortalized keratinocytes with Akt kinase inhibitor reduced hnRNP L binding to HPV16 mRNAs and induced HPV16 L1 mRNA production. Finally, deletion of the hnRNP L binding sites in HPV16 subgenomic expression plasmids resulted in activation of HPV16 late gene expression. In conclusion, the Akt kinase inhibits HPV16 late gene expression at the level of RNA processing by controlling the RNA-binding protein hnRNP L. We speculate that Akt kinase activity upholds an intracellular milieu that favours HPV16 early gene expression and suppresses HPV16 late gene expression. PMID:28934469

Presenting symptoms and clinical findings in HPV-positive and HPV-negative oropharyngeal cancer patients.

PubMed

Carpén, Timo; Sjöblom, Anni; Lundberg, Marie; Haglund, Caj; Markkola, Antti; Syrjänen, Stina; Tarkkanen, Jussi; Mäkitie, Antti; Hagström, Jaana; Mattila, Petri

2018-05-01

Oropharyngeal squamous cell carcinoma (OPSCC) is divided in two different disease entities depending on HPV involvement. We investigated differences in presenting symptoms and clinical findings in patients with HPV-positive and -negative OPSCC tumors. Altogether 118 consecutive patients diagnosed with primary OPSCC between 2012 and 2014 at the Helsinki University Hospital were included. HPV-status of the tumors was assessed by PCR detection of HPV DNA and immunostaining with p16-INK4a antibody. Fifty-one (47.7%) of the patients had HPV-positive and 56 (52.3%) HPV-negative tumors. Forty-nine (49/51, 96.1%) of the HPV+ tumors were also p16+ showing high concordance. The most common presenting symptom among HPV+/p16+ patients was a neck mass (53.1%), whereas any sort of pain in the head and neck area was more frequently related to the HPV-/p16- (60.0%) group. HPV+/p16+ tumors had a tendency to locate in the tonsillar complex and more likely had already spread into regional lymph nodes compared with HPV-/p16- tumors. Smoking and heavy alcohol consumption were significantly more common among HPV-/p16- patients but also rather common among HPV+/p16+ patients. This analysis of symptoms and signs confirm that OPSCC can be dichotomized in two distinct disease entities as defined by HPV status.

High Burden of Human Papillomavirus (HPV) Infection among Young Women in KwaZulu-Natal, South Africa.

PubMed

Ebrahim, Sumayyah; Mndende, Xolani K; Kharsany, Ayesha B M; Mbulawa, Zizipho Z A; Naranbhai, Vivek; Frohlich, Janet; Werner, Lise; Samsunder, Natasha; Karim, Quarraisha Abdool; Williamson, Anna-Lise

2016-01-01

HPV infection causes cervical cancer, yet information on prevalence and risk factors for HPV in Africa remain sparse. This study describes the prevalence of HPV genotypes and risk factors associated with HPV among young women ≤ 30 years of age in KwaZulu-Natal (KZN), South Africa. Cervicovaginal lavage samples were tested for HPV genotypes in 224 women enrolled in a prospective cohort study. Clinical, behavioural and demographic data were collected. We measured prevalence of HPV genotypes and using logistic regression, examined for factors associated with HPV. Median age of participants was 21 years [interquartile range (IQR):18-23]. The overall prevalence of HPV was 76.3% (171/224) with multiple and single genotypes prevalent in 56.3% and 20.1% of women respectively. Proportion of women with high-risk genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56 and 58) was 54.5%. Women not living with their partner [adjusted odds ratio (aOR)] = 3.42 95% CI1.22-9.60; p = 0.019), was significantly associated with HPV infection and high-risk HPV genotype infection. The high burden of HPV and associated risk behaviours highlight the need to intensify behavioural interventions to prevent HPV acquisition in young women. The large scale delivery of HPV vaccine should be prioritised to prevent HPV acquisition and reduce HPV-related morbidity.

Knowledge of HPV and HPV Vaccine among Women Ages 19 to 26.

PubMed

Unger, Zoe; Maitra, Abby; Kohn, Julia; Devaskar, Sangita; Stern, Lisa; Patel, Ashlesha

2015-01-01

To describe knowledge about human papillomavirus (HPV) and HPV vaccination among women ages 19 to 26 seeking a variety of services at reproductive health centers. A secondary objective was to identify common sources of HPV information. Ten reproductive health centers enrolled 365 women ages 19 to 26 in a randomized, controlled trial to determine the effect of automated reminder messages on HPV vaccine completion. Using responses from a 61-item self-administered baseline questionnaire completed before initiating the HPV vaccine, this subanalysis assessed participants' knowledge regarding HPV and the HPV vaccine. Knowledge of HPV prevention, transmission, and disease outcomes among the study population was highly variable. The mean HPV knowledge score was 11.0 of a possible 19 (SD = 3.8). Most participants (77%) had heard of the HPV vaccine before completing the questionnaire and indicated that their primary sources of information about the vaccine were television ads (61%), health care providers (52%), and friends (45%). Despite a relatively high awareness of the vaccine, specific knowledge regarding HPV and the HPV vaccine varied substantially and participant scores highlighted knowledge gaps among vaccine-eligible young women. Media, health care providers, and friends were identified by participants as sources of information and may influence their knowledge of HPV and the HPV vaccine. Copyright © 2015 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Not just a woman's business! Understanding men and women's knowledge of HPV, the HPV vaccine, and HPV-associated cancers.

PubMed

Osazuwa-Peters, Nosayaba; Adjei Boakye, Eric; Mohammed, Kahee A; Tobo, Betelihem B; Geneus, Christian J; Schootman, Mario

2017-06-01

Few studies have included men when assessing differences in knowledge about HPV, and HPV-associated cancers. We examined gender differences in knowledge about HPV, HPV vaccine, and HPV-associated cancers. Multivariable logistic regression models were used to analyze data of 3,677 survey respondents aged 18 years and older from the 2014 Health Information National Trends Survey. Covariates included age, race/ethnicity, marital status, education, income level, regular provider, general health, internet use, and family structure aged 9 to 27 years. Analyses were conducted in 2015. Sixty-four percent of respondents had heard of HPV and the HPV vaccine. Seventy-eight percent of respondents knew HPV causes cervical cancer, but only 29% knew it causes penile cancer, 26% knew it causes anal cancer, and 30% knew it causes oral cancer. In multivariable analyses, males were less likely to have heard of HPV (aOR: 0.33; 95% CI: 0.25-0.45), and less likely to have heard of the HPV vaccine (aOR: 0.24; 95% CI: 0.18-0.32) compared to females. No differences existed between males and females regarding knowledge about HPV-associated cancers. In conclusion, knowledge of HPV, the vaccine, and HPV-associated cancers in both males and females in the United States remains very low, especially among men. Copyright © 2017 Elsevier Inc. All rights reserved.

Ethnically diverse female university students' knowledge and attitudes toward human papillomavirus (HPV), HPV vaccination and cervical cancer.

PubMed

Wong, Li Ping; Sam, I-Ching

2010-01-01

Cervical HPV is the most common sexually transmitted disease among college-age women. This study aimed to assess knowledge and attitudes towards HPV infection, HPV vaccination and cervical cancer among female university students, to provide insight into development of HPV educational information. A cross-sectional survey using a convenience sample. A total of 1083 ethnically diverse female students attending a public university were approached and 650 were interviewed. Knowledge regarding HPV, HPV vaccination, cervical screening and cervical cancer risk factors was remarkably poor. Across the sample, the mean total knowledge score (14-item) was only 3.25 (S.D. +/-2.41; 95% CI 3.07-3.44). Only 10.3% had heard of the newly released HPV vaccine. Approximately 48% of participants indicated an intention to receive an HPV vaccine. Intention to receive an HPV vaccine was significantly associated with knowledge of HPV and genital warts (OR 1.53; 95% CI 1.25-1.88), and knowledge of cervical screening and cervical cancer risk factors (OR 1.21; 95% CI 1.11-1.33). Of those who refused HPV vaccination, 50.9% doubted the safety and efficacy of the new vaccine, and 41.5% perceived themselves as not at risk of HPV infection. The findings suggest that providing education about the etiology of cervical cancer and the HPV link is an essential component to enhance HPV vaccine uptake.

Comparison of long-term immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18-45 years: End-of-study analysis of a Phase III randomized trial

PubMed Central

Einstein, Mark H; Takacs, Peter; Chatterjee, Archana; Sperling, Rhoda S; Chakhtoura, Nahida; Blatter, Mark M; Lalezari, Jacob; David, Marie-Pierre; Lin, Lan; Struyf, Frank; Dubin, Gary

2014-01-01

The observer-blind, randomized, age-stratified, head-to-head study (NCT00423046) comparing immunogenicity and safety of HPV-16/18 and HPV-6/11/16/18 vaccines in healthy women aged 18-45 y was completed. Five y after vaccination, in subjects from the Month 60 according-to-protocol cohort (seronegative and DNA negative for HPV type analyzed at baseline), serum neutralizing antibody (nAb) responses induced by HPV-16/18 vaccine remained 7.8-fold (18-26-y stratum), 5.6-fold (27-35-y stratum) and 2.3-fold (36-45-y stratum) higher than those induced by HPV-6/11/16/18 vaccine for HPV-16. For HPV-18, the fold differences were 12.1, 13.0 and 7.8, respectively. At Month 60, all (100%) subjects in HPV-16/18 vaccine group and the majority (95.7%-97.5%) in HPV-6/11/16/18 vaccine group were seropositive for HPV-16. For HPV-18, the majority (98.1%-100%) of subjects in HPV-16/18 vaccine group were seropositive; however, seropositivity rates in HPV-6/11/16/18 vaccine group decreased considerably (61.1%-76.9%) across the 3 age strata. In the total vaccinated cohort (received ≥ 1 dose regardless of baseline HPV serostatus and DNA status), geometric mean titers for anti-HPV-16 and anti-HPV-18 nAb were higher in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. Based on the 5-y data, piece-wise and modified power-law models predicted a longer durability of nAb response for HPV-16/18 vaccine compared to HPV-6/11/16/18 vaccine. Beyond the differences apparent between the vaccines in terms of immunogenicity and modeled persistence of antibody responses, comparative studies including clinical endpoints would be needed to determine whether differences exist in duration of vaccine-induced protection. PMID:25483701

Comparison of long-term immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18-45 years: end-of-study analysis of a Phase III randomized trial.

PubMed

Einstein, Mark H; Takacs, Peter; Chatterjee, Archana; Sperling, Rhoda S; Chakhtoura, Nahida; Blatter, Mark M; Lalezari, Jacob; David, Marie-Pierre; Lin, Lan; Struyf, Frank; Dubin, Gary

2014-01-01

The observer-blind, randomized, age-stratified, head-to-head study (NCT00423046) comparing immunogenicity and safety of HPV-16/18 and HPV-6/11/16/18 vaccines in healthy women aged 18-45 y was completed. Five y after vaccination, in subjects from the Month 60 according-to-protocol cohort (seronegative and DNA negative for HPV type analyzed at baseline), serum neutralizing antibody (nAb) responses induced by HPV-16/18 vaccine remained 7.8-fold (18-26-y stratum), 5.6-fold (27-35-y stratum) and 2.3-fold (36-45-y stratum) higher than those induced by HPV-6/11/16/18 vaccine for HPV-16. For HPV-18, the fold differences were 12.1, 13.0 and 7.8, respectively. At Month 60, all (100%) subjects in HPV-16/18 vaccine group and the majority (95.7%-97.5%) in HPV-6/11/16/18 vaccine group were seropositive for HPV-16. For HPV-18, the majority (98.1%-100%) of subjects in HPV-16/18 vaccine group were seropositive; however, seropositivity rates in HPV-6/11/16/18 vaccine group decreased considerably (61.1%-76.9%) across the 3 age strata. In the total vaccinated cohort (received ≥1 dose regardless of baseline HPV serostatus and DNA status), geometric mean titers for anti-HPV-16 and anti-HPV-18 nAb were higher in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. Based on the 5-y data, piece-wise and modified power-law models predicted a longer durability of nAb response for HPV-16/18 vaccine compared to HPV-6/11/16/18 vaccine. Beyond the differences apparent between the vaccines in terms of immunogenicity and modeled persistence of antibody responses, comparative studies including clinical endpoints would be needed to determine whether differences exist in duration of vaccine-induced protection.

High Prevalence of Anal Canal High-Risk Human Papillomavirus Infection in Patients With Crohn's Disease.

PubMed

Vuitton, Lucine; Jacquin, Elise; Parmentier, Anne-Laure; Crochet, Elise; Fein, Francine; Dupont-Gossart, Anne-Claire; Plastaras, Laurianne; Bretagne, Charles-Henri; Mauny, Frédéric; Koch, Stéphane; Prétet, Jean-Luc; Mougin, Christiane; Valmary-Degano, Séverine

2018-03-15

The increasing incidence of anal canal carcinomas requires better knowledge on anal human papillomavirus (HPV) infection. We aimed to assess anal canal HPV infection prevalence and risk factors among patients seen at a gastroenterology department in France. We analyzed anal tissue samples collected from 469 consecutive patients (median age 54 years, 52% women), including 112 who received immunosuppressant therapies and 101 with inflammatory bowel disease (70 with Crohn's disease), who underwent colonoscopy examinations from April 1, 2012 to April 30, 2015. HPV was detected and genotyped using the INNO-LiPA assay, and we collected medical and demographic data from all subjects. Risk factors for any HPV, high-risk HPV (HR-HPV) and HPV16 infection were assessed by bivariate and multivariate analysis. The primary outcomes association of HR-HPV or HPV16 with medical and demographic features. We detected HPV DNA in anal tissues from 34% of the subjects and HR-HPV in 18%. HPV16 was the most prevalent genotype (detected in 7%), followed by HPV51, HPV52, and HPV39. HR-HPV was detected in a significantly higher proportion of samples from women (23.1%) than men (12.8%) (P = .0035); HR-HPV and HPV16 were detected in a significantly higher proportion of patients with Crohn's disease (30.0%) than without (18.1%) (P = .005). Female sex, history of sexually transmitted disease, lifetime and past year-number of sexual partners, active smoking, and immunosuppressive therapies were independent risk factors for anal HR-HPV infection in multivariate analysis. One third of patients who underwent colonoscopy at a gastroenterology department were found to have anal canal HPV infection. We detected HR-HPV infection in almost 20% of patients and in a significantly higher proportion of patients with Crohn's disease than without. Increasing our knowledge of HPV infection of anal tissues could help physicians identify populations at risk and promote prophylaxis with vaccination and adequate screening. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Design, Fabrication and Characterization of A Bi-Frequency Co-Linear Array

PubMed Central

Wang, Zhuochen; Li, Sibo; Czernuszewicz, Tomasz J; Gallippi, Caterina M.; Liu, Ruibin; Geng, Xuecang

2016-01-01

Ultrasound imaging with high resolution and large penetration depth has been increasingly adopted in medical diagnosis, surgery guidance, and treatment assessment. Conventional ultrasound works at a particular frequency, with a −6 dB fractional bandwidth of ~70 %, limiting the imaging resolution or depth of field. In this paper, a bi-frequency co-linear array with resonant frequencies of 8 MHz and 20 MHz was investigated to meet the requirements of resolution and penetration depth for a broad range of ultrasound imaging applications. Specifically, a 32-element bi-frequency co-linear array was designed and fabricated, followed by element characterization and real-time sectorial scan (S-scan) phantom imaging using a Verasonics system. The bi-frequency co-linear array was tested in four different modes by switching between low and high frequencies on transmit and receive. The four modes included the following: (1) transmit low, receive low, (2) transmit low, receive high, (3) transmit high, receive low, (4) transmit high, receive high. After testing, the axial and lateral resolutions of all modes were calculated and compared. The results of this study suggest that bi-frequency co-linear arrays are potential aids for wideband fundamental imaging and harmonic/sub-harmonic imaging. PMID:26661069

Persistence of memory B-cell and T-cell responses to the quadrivalent HPV vaccine in HIV-infected children.

PubMed

Weinberg, Adriana; Huang, Sharon; Moscicki, Anna-Barbara; Saah, Afred; Levin, Myron J

2018-04-24

To determine the magnitude and persistence of quadrivalent human papillomavirus (HPV)16 and HPV18 B-cell and T-cell memory after three or four doses of quadrivalent HPV vaccine (QHPV) in HIV-infected children. Seventy-four HIV-infected children immunized with four doses and 23 with three doses of QHPV had HPV16 and HPV18 IgG B-cell and IFNγ and IL2 T-cell ELISPOT performed at 2, 3.5 and 4-5 years after the last dose. HPV16 and HPV18 T-cell responses were similar in both treatment groups, with higher responses to HPV16 vs. HPV18. These HPV T-cell responses correlated with HIV disease characteristics at the study visits. Global T-cell function declined over time as measured by nonspecific mitogenic stimulation. B-cell memory was similar across treatment groups and HPV genotypes. There was a decline in HPV-specific B-cell memory over time that reached statistical significance for HPV16 in the four-dose group. B-cell and T-cell memory did not significantly differ after either three or four doses of QHPV in HIV-infected children. The clinical consequences of decreasing global T-cell function and HPV B-cell memory over time in HIV-infected children requires further investigation.

Performance of 21 HPV vaccination programs implemented in low and middle-income countries, 2009–2013

PubMed Central

2014-01-01

Background Cervical cancer is the third most common cancer in women worldwide, with high incidence in lowest income countries. Vaccination against Human Papilloma Virus (HPV) may help to reduce the incidence of cervical cancer. The aim of the study was to analyze HPV vaccination programs performance implemented in low and middle-income countries. Methods The Gardasil Access Program provides HPV vaccine at no cost to help national institutions gain experience implementing HPV vaccination. Data on vaccine delivery model, number of girls vaccinated, number of girls completing the three-dose campaign, duration of vaccination program, community involvement and sensitization strategies were collected from each program upon completion. Vaccine Uptake Rate (VUR) and Vaccine Adherence between the first and third doses (VA) rate were calculated. Multivariate linear regressions analyses were fitted. Results Twenty-one programs were included in 14 low and middle-income countries. Managing institutions were non-governmental organizations (NGOs) (n = 8) or Ministries of Health (n = 13). Twelve programs were school-based, five were health clinic-based and four utilized a mixed model. A total of 217,786 girls received a full course of vaccination. Mean VUR was 88.7% (SD = 10.5) and VA was 90.8% (SD = 7.3). The mean total number of girls vaccinated per program-month was 2,426.8 (SD = 2,826.6) in school model, 335.1 (SD = 202.5) in the health clinic and 544.7 (SD = 369.2) in the mixed models (p = 0.15). Community involvement in the follow-up of girls participating in the vaccination campaign was significantly associated with VUR. Multivariate analyses identified school-based (β = 13.35, p = 0.001) and health clinic (β = 13.51, p = 0.03) models, NGO management (β = 14.58, p < 10-3) and duration of program vaccination (β = -1.37, p = 0.03) as significant factors associated with VUR. Conclusion School and health clinic-based models appeared as predictive factors for vaccination coverage, as was management by an NGO; program duration could play a role in the program’s effectiveness. Results suggest that HPV vaccine campaigns tailored to meet the needs of communities can be effective. These results may be useful in the development of national HPV vaccination policies in low and middle-income countries. PMID:24981818

Association of human papillomavirus infection and abnormal anal cytology among HIV-infected MSM in Beijing, China.

PubMed

Yang, Yu; Li, Xiangwei; Zhang, Zhihui; Qian, Han-Zhu; Ruan, Yuhua; Zhou, Feng; Gao, Cong; Li, Mufei; Jin, Qi; Gao, Lei

2012-01-01

In the recent years, dramatic increases in HIV transmission among men who have sex with men (MSM) have been observed in China. Human papillomavirus (HPV) infection related anal cancer is more common among HIV-infected MSM as compared to the general population. However, HPV infection and anal cytology has been rarely studied in HIV-infected MSM in China. HIV-infected MSM in Beijing, China were invited to participate in this study between January and April 2011. Anal swabs were collected for examining cytology and HPV genotypes. Ninety-five eligible participants with complete questionnaire and laboratory data were included in the analyses. Thirty six of them (37.9%) showed abnormal anal cytology as follows: atypical squamous cells of undetermined significance (ASC-US) in 19 (20.0%), atypical squamous cells but cannot exclude HSIL (ASC-H) in 1 (1.1%), low-grade squamous intraepithelial lesion (LSIL) in 15 (15.8%), and high-grade squamous intraepithelial lesion (HSIL) in 1 (1.1%). HPV6 (20.0%), HPV16 (10.9%), HPV56 (10.9%), HPV52 (9.1%) and HPV39 (9.1%) were observed most frequently among those with normal anal cytology, while different distribution was found in the ones with abnormal anal cytology as HPV6 (19.4%), HPV16 (19.4%), HPV45 (16.7%), HPV52 (16.7%) and HPV18 (11.1%). In addition, HPV16, HPV45, HPV52 and HPV18 were the most frequent high-risk types in patients with abnormal anal cytology. HPV multiplicity was found to be significantly related to the prevalence of abnormal anal cytology (p for trend = 0.04). High prevalence of HPV infection and abnormal anal cytology was observed among HIV-infected MSM in China. Infection of multiple HPV types or high-risk types was found to be associated with an increased risk of abnormal anal cytology.

Association of Human Papillomavirus Infection and Abnormal Anal Cytology among HIV-Infected MSM in Beijing, China

PubMed Central

Zhang, Zhihui; Qian, Han-Zhu; Ruan, Yuhua; Zhou, Feng; Gao, Cong; Li, Mufei; Jin, Qi; Gao, Lei

2012-01-01

Background In the recent years, dramatic increases in HIV transmission among men who have sex with men (MSM) have been observed in China. Human papillomavirus (HPV) infection related anal cancer is more common among HIV-infected MSM as compared to the general population. However, HPV infection and anal cytology has been rarely studied in HIV-infected MSM in China. Methods HIV-infected MSM in Beijing, China were invited to participate in this study between January and April 2011. Anal swabs were collected for examining cytology and HPV genotypes. Results Ninety-five eligible participants with complete questionnaire and laboratory data were included in the analyses. Thirty six of them (37.9%) showed abnormal anal cytology as follows: atypical squamous cells of undetermined significance (ASC-US) in 19 (20.0%), atypical squamous cells but cannot exclude HSIL (ASC-H) in 1 (1.1%), low-grade squamous intraepithelial lesion (LSIL) in 15 (15.8%), and high-grade squamous intraepithelial lesion (HSIL) in 1 (1.1%). HPV6 (20.0%), HPV16 (10.9%), HPV56 (10.9%), HPV52 (9.1%) and HPV39 (9.1%) were observed most frequently among those with normal anal cytology, while different distribution was found in the ones with abnormal anal cytology as HPV6 (19.4%), HPV16 (19.4%), HPV45 (16.7%), HPV52 (16.7%) and HPV18 (11.1%). In addition, HPV16, HPV45, HPV52 and HPV18 were the most frequent high-risk types in patients with abnormal anal cytology. HPV multiplicity was found to be significantly related to the prevalence of abnormal anal cytology (p for trend = 0.04). Conclusions High prevalence of HPV infection and abnormal anal cytology was observed among HIV-infected MSM in China. Infection of multiple HPV types or high-risk types was found to be associated with an increased risk of abnormal anal cytology. PMID:22558293

HPV prevalence and genotypes in different histological subtypes of cervical adenocarcinoma, a worldwide analysis of 760 cases.

PubMed

Pirog, Edyta C; Lloveras, Belen; Molijn, Anco; Tous, Sara; Guimerà, Núria; Alejo, Maria; Clavero, Omar; Klaustermeier, Joellen; Jenkins, David; Quint, Wim Gv; Xavier Bosch, Francesc; Alemany, Laia; de Sanjosé, Silvia

2014-12-01

The goal of our study was to provide comprehensive data on the worldwide human papillomavirus (HPV) genotype distribution in patients with invasive cervical adenocarcinoma in correlation with histologic tumor subtypes, geographical location, patients' age, and duration of sample storage. Paraffin-embedded samples of 760 cervical adenocarcinoma cases were collected worldwide. A three-level pathology review of cases was performed to obtain consensus histologic diagnoses and 682 cases were determined to be eligible for further analysis. HPV DNA detection and genotyping was performed using SPF-10/DEIA/LiPA(25) system (version 1). Classic cervical adenocarcinoma accounted for 83.1% of cases, while rare histological variants accounted for a few percent of cases individually. HPV positivity varied significantly between the different histologic tumor subtypes. Classic cervical adenocarcinoma showed high HPV positivity (71.8%), while other adenocarcinoma types had significantly lower HPV prevalence (endometrioid 27.3%, serous 25%, clear cell 20%, not otherwise specified 13.9%, and minimal deviation 8.3%). In all, 91.8% of HPV-positive tumors showed the presence of a single viral type and in 7% of cases multiple viral types were detected. Three HPV genotypes, HPV 16, 18, and 45, dominated in all adenocarcinomas and together accounted for 94.1% of HPV-positive tumors. HPV16 was the most common and found in 50.9% of HPV-positive cases, followed by HPV18 (31.6%) and HPV45 (11.6%). HPV prevalence varied depending on geographical region, patient age, and sample storage time. Tumors from older patients and tumor samples with longer storage time showed lower HPV prevalence. Our results indicate that HPV vaccines may prevent up to 82.5% (HPV16/18) and up to 95.3% (9-valent vaccine) of HPV-positive cervical adenocarcinomas, mostly the classic type. HPV testing and vaccination will not provide full coverage for a very small subset of classical adenocarcinomas and most of the rare tumor variants such as clear cell, serous, endometrioid, and minimal deviation.

In vitro biological activities of the E6 and E7 genes vary among human papillomaviruses of different oncogenic potential.

PubMed Central

Barbosa, M S; Vass, W C; Lowy, D R; Schiller, J T

1991-01-01

Human papillomavirus type 16 (HPV-16) and HPV-18 are often detected in cervical carcinomas, while HPV-6, although frequently present in benign genital lesions, is only rarely present in cancers of the cervix. Therefore, infections with HPV-16 and HPV-18 are considered high risk and infection with HPV-6 is considered low risk. We found, by using a heterologous promoter system, that expression of the E7 transforming protein differs between high- and low-risk HPVs. In high-risk HPV-16, E7 is expressed from constructs containing the complete upstream E6 open reading frame. In contrast, HPV-6 E7 was efficiently translated only when E6 was deleted. By using clones in which the coding regions of HPV-6, HPV-16, and HPV-18 E7s were preceded by identical leader sequences, we found that the ability of the E7 gene products to induce anchorage-independent growth in rodent fibroblasts correlated directly with the oncogenic association of the HPV types. By using an immortalization assay of normal human keratinocytes that requires complementation of E6 and E7, we found that both E6 and E7 of HPV-18 could complement the corresponding gene from HPV-16. However, neither E6 nor E7 from HPV-6 was able to substitute for the corresponding gene of HPV-16 or HPV-18. Our results suggest that multiple factors, including lower intrinsic biological activity of E6 and E7 and differences in the regulation of their expression, account for the low activity of HPV-6, in comparison with HPV-16 and HPV-18, in in vitro assays. These same factors may, in part, account for the apparent difference in oncogenic potential between these viruses. Images PMID:1845889

Human papillomavirus and oral squamous cell carcinoma: A review of HPV-positive oral squamous cell carcinoma and possible strategies for future.

PubMed

Jiang, Shan; Dong, Yong

Oral squamous cell carcinoma (OSCC) is a common cancer worldwide. Besides tobacco use and alcohol consumption, human papillomavirus (HPV) infection has also been identified as a risk factor for OSCC recently. The OSCC incidence has increased in recent years, especially among younger women. The purpose of this article is to review clinical and epidemiological studies on the association between HPV infection and OSCCs, and the efficacy of HPV vaccine, so as to provide possible policy implications for preventing HPV-positive OSCC. It is necessary to review the present related body of knowledge to determine whether the association between HPV infection and OSCC has been thoroughly studied. The study was based on literature review. Studies were identified using electronic databases including MEDLINE, PubMed, EMBASE, etc. The inclusion and exclusion criteria were based on consultation from a panel of experts in this area and carefully designed. Based on a systematic review of literatures, HPV infection is a possible cause for the incidence of HPV-positive OSCCs. The prevalence of HPV infection possibly contributed to the increasing trends of HPV-positive OSCCs. Oral HPV infection is a form of HPV transmission. Oral sex behaviors and open-mouthed kissing are probably reasons for oral HPV infection. We also have some epidemiological evidences proving that HPV vaccine provides a possible solution for preventing oral HPV infection. Increased awareness of HPV-positive OSCCs is essential due to the severity of this problem. Biological and epidemiological data regarding the link between sexual behavior and HPV-associated cancers indicate a probable connection, although definitive data are needed. Future studies are needed to investigate the mechanisms of how HPV infection causes HPV-positive OSCCs, whether HPV vaccine provides a prevention for OSCCs, and other important issues. Copyright © 2017 Elsevier Inc. All rights reserved.

Incidence and risk factors of HPV-related and HPV-unrelated Head and Neck Squamous Cell Carcinoma in HIV-infected individuals.

PubMed

Beachler, Daniel C; Abraham, Alison G; Silverberg, Michael J; Jing, Yuezhou; Fakhry, Carole; Gill, M John; Dubrow, Robert; Kitahata, Mari M; Klein, Marina B; Burchell, Ann N; Korthuis, P Todd; Moore, Richard D; D'Souza, Gypsyamber

2014-12-01

To examine the risk and trends of HPV-related and HPV-unrelated Head and Neck Squamous Cell Carcinoma (HNSCC) in HIV-infected individuals and assess whether immunosuppression (measured through CD4 cell count) and other risk factors impact HNSCC risk. Incident HNSCCs at HPV-related and HPV-unrelated anatomic sites were detected in HIV-infected participants from pooled data from 17 prospective studies in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) between 1996 and 2009. HNSCC cases were validated using chart review or cancer registry matching. Risk factors for incident HPV-related and HPV-unrelated HNSCC were explored using mixed effects Poisson regression in a full prospective analysis, and the effect of CD4 prior to cancer diagnosis was examined in a nested case control analysis. 66 HPV-related and 182 HPV-unrelated incident HNSCCs were detected among 82,375 HIV-infected participants. Standardized incidence ratios (SIRs) for both HPV-related (SIR=3.2, 95%CI=2.5-3.4) and HPV-unrelated (SIR=3.0, 95%CI=2.5-4.1) HNSCC were significantly elevated in HIV-infected individuals compared with the US general population. Between 1996 and 2009, the age-standardized HPV-related HNSCC incidence increased non-significantly from 6.8 to 11.4per 100,000 person-years (p-trend=0.31) while the age-standardized incidence of HPV-unrelated HNSCC decreased non-significantly from 41.9 to 29.3 per 100,000 person-years (p-trend=0.16). Lower CD4 cell count prior to cancer diagnosis was significantly associated with increased HPV-related and HPV-unrelated HNSCC risk. The standardized incidence of HPV-related and HPV-unrelated HNSCC are both elevated in HIV-infected individuals. Immunosuppression may have a role in the development of both HPV-related and HPV-unrelated HNSCC. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sensitivity and specificity of antibodies against HPV16 E6 and other early proteins for the detection of HPV16-driven oropharyngeal squamous cell carcinoma.

PubMed

Holzinger, Dana; Wichmann, Gunnar; Baboci, Lorena; Michel, Angelika; Höfler, Daniela; Wiesenfarth, Manuel; Schroeder, Lea; Boscolo-Rizzo, Paolo; Herold-Mende, Christel; Dyckhoff, Gerhard; Boehm, Andreas; Del Mistro, Annarosa; Bosch, Franz X; Dietz, Andreas; Pawlita, Michael; Waterboer, Tim

2017-06-15

To determine the sensitivity and specificity of HPV16 serology as diagnostic marker for HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), 214 HNSCC patients from Germany and Italy with fresh-frozen tumor tissues and sera collected before treatment were included in this study. Hundred and twenty cancer cases were from the oropharynx and 94 were from head and neck cancer regions outside the oropharynx (45 oral cavity, 12 hypopharynx and 35 larynx). Serum antibodies to early (E1, E2, E6 and E7) and late (L1) HPV16 proteins were analyzed by multiplex serology and were compared to tumor HPV RNA status as the gold standard. A tumor was defined as HPV-driven in the presence of HPV16 DNA and HPV16 transformation-specific RNA transcript patterns (E6*I, E1 ∧ E4 and E1C). Of 120 OPSCC, 66 (55%) were HPV16-driven. HPV16 E6 seropositivity was the best predictor of HPV16-driven OPSCC (diagnostic accuracy 97% [95%CI 92-99%], Cohen's kappa 0.93 [95%CI 0.8-1.0]). Of the 66 HPV-driven OPSCC, 63 were HPV16 E6 seropositive, compared to only one (1.8%) among the 54 non-HPV-driven OPSCC, resulting in a sensitivity of 96% (95%CI 88-98) and a specificity of 98% (95%CI 90-100). Of 94 HNSCC outside the oropharynx, six (6%) were HPV16-driven. In these patients, HPV16 E6 seropositivity had lower sensitivity (50%, 95%CI 19-81), but was highly specific (100%, 95%CI 96-100). In conclusion, HPV16 E6 seropositivity appears to be a highly reliable diagnostic marker for HPV16-driven OPSCC with very high sensitivity and specificity, but might be less sensitive for HPV16-driven HNSCC outside the oropharynx. © 2017 UICC.

HPV vaccination coverage of teen girls: the influence of health care providers.

PubMed

Smith, Philip J; Stokley, Shannon; Bednarczyk, Robert A; Orenstein, Walter A; Omer, Saad B

2016-03-18

Between 2010 and 2014, the percentage of 13-17 year-old girls administered ≥3 doses of the human papilloma virus (HPV) vaccine ("fully vaccinated") increased by 7.7 percentage points to 39.7%, and the percentage not administered any doses of the HPV vaccine ("not immunized") decreased by 11.3 percentage points to 40.0%. To evaluate the complex interactions between parents' vaccine-related beliefs, demographic factors, and HPV immunization status. Vaccine-related parental beliefs and sociodemographic data collected by the 2010 National Immunization Survey-Teen among teen girls (n=8490) were analyzed. HPV vaccination status was determined from teens' health care provider (HCP) records. Among teen girls either unvaccinated or fully vaccinated against HPV, teen girls whose parent was positively influenced to vaccinate their teen daughter against HPV were 48.2 percentage points more likely to be fully vaccinated. Parents who reported being positively influenced to vaccinate against HPV were 28.9 percentage points more likely to report that their daughter's HCP talked about the HPV vaccine, 27.2 percentage points more likely to report that their daughter's HCP gave enough time to discuss the HPV shot, and 43.4 percentage points more likely to report that their daughter's HCP recommended the HPV vaccine (p<0.05). Among teen girls administered 1-2 doses of the HPV vaccine, 87.0% had missed opportunities for HPV vaccine administration. Results suggest that an important pathway to achieving higher ≥3 dose HPV vaccine coverage is by increasing HPV vaccination series initiation though HCP talking to parents about the HPV vaccine, giving parents time to discuss the vaccine, and by making a strong recommendation for the HPV. Also, HPV vaccination series completion rates may be increased by eliminating missed opportunities to vaccinate against HPV and scheduling additional follow-up visits to administer missing HPV vaccine doses. Published by Elsevier Ltd.

Deconstructing Human Papillomavirus (HPV) Knowledge: Objective and Perceived Knowledge in Males' Intentions to Receive the HPV Vaccine

ERIC Educational Resources Information Center

Krawczyk, Andrea; Stephenson, Ellen; Perez, Samara; Lau, Elsa; Rosberger, Zeev

2013-01-01

Background: The human papillomavirus (HPV) vaccine was recently approved for men. To effectively tailor HPV education efforts toward men, it is important to understand what men know about HPV and how this knowledge relates to their decision to receive the vaccine. This study examines how objective HPV knowledge, objective HPV vaccine knowledge,…

Cellular immune responses to HPV-18, -31, and -53 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pinto, Ligia A.; Viscidi, Raphael; Harro, Clayton D.

Human papillomavirus-like particles (HPV VLP) are candidate vaccines that have shown to be efficacious in reducing infection and inducing robust antiviral immunity. Neutralizing antibodies generated by vaccination are largely type-specific, but little is known about the type-specificity of cellular immune responses to VLP vaccination. To determine whether vaccination with HPV-16 L1VLP induces cellular immunity to heterologous HPV types (HPV-18, HPV-31, and HPV-53), we examined proliferative and cytokine responses in vaccine (n = 11) and placebo (n = 5) recipients. Increased proliferative and cytokine responses to heterologous types were observed postvaccination in some individuals. The proportion of women responding to heterologousmore » types postvaccination (36%-55%) was lower than that observed in response to HPV-16 (73%). Response to HPV-16 VLP predicted response to other types. The strongest correlations in response were observed between HPV-16 and HPV-31, consistent with their phylogenetic relatedness. In summary, PBMC from HPV-16 VLP vaccine recipients can respond to L1VLP from heterologous HPV types, suggesting the presence of conserved T cell epitopes.« less

Effect of human papilloma virus expression on clinical course of laryngeal papilloma.

PubMed

Kim, Kwang Moon; Cho, Nam Hoon; Choi, Hong Shik; Kim, Young Ho; Byeon, Hyung Kwon; Min, Hyun Jin; Kim, Se-Heon

2008-10-01

Our observations suggest that human papilloma virus (HPV) 6/11 is the main causative agent of laryngeal papilloma and that detection of active HPV DNA expression may be helpful in identifying patients with aggressive recurrent laryngeal papilloma. HPV is assumed to be the main causative agent of this disease. We investigated the expression of the entire genotype of HPV in cases of laryngeal papilloma and correlated their expression with the clinical course of the disease. Seventy cases of laryngeal papilloma were evaluated for the presence of the HPV genome by in situ hybridization (ISH) using wide-spectrum HPV DNA probe. Specific types of HPV infection were determined by DNA ISH using type-specific HPV DNA probes (HPV 6, 11, 16, 18, 31, 33). Separate analyses were conducted comparing viral types, frequency of recurrences and duration of disease-free periods. We detected HPV DNA in 40 of the 70 laryngeal papilloma cases (57%). In particular, HPV DNA was detected in 75% of the juvenile types. There were significant associations between HPV and laryngeal papilloma (p<0.01). Among the HPV-positive cases, major specific types were HPV 6/11 (97%). Significant associations were also noted between viral expression and clinical course.

The human papillomavirus type 58 E7 oncoprotein modulates cell cycle regulatory proteins and abrogates cell cycle checkpoints

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Weifang; Department of Microbiology, School of Medicine, Shandong University, Jinan, Shandong; Li Jing

2010-02-05

HPV type 58 (HPV-58) is the third most common HPV type in cervical cancer from Eastern Asia, yet little is known about how it promotes carcinogenesis. In this study, we demonstrate that HPV-58 E7 significantly promoted the proliferation and extended the lifespan of primary human keratinocytes (PHKs). HPV-58 E7 abrogated the G1 and the postmitotic checkpoints, although less efficiently than HPV-16 E7. Consistent with these observations, HPV-58 E7 down-regulated the cellular tumor suppressor pRb to a lesser extent than HPV-16 E7. Similar to HPV-16 E7 expressing PHKs, Cdk2 remained active in HPV-58 E7 expressing PHKs despite the presence of elevatedmore » levels of p53 and p21. Interestingly, HPV-58 E7 down-regulated p130 more efficiently than HPV-16 E7. Our study demonstrates a correlation between the ability of down-regulating pRb/p130 and abrogating cell cycle checkpoints by HPV-58 E7, which also correlates with the biological risks of cervical cancer progression associated with HPV-58 infection.« less

Factors influencing the recommendation of the Human Papillomavirus vaccine by South African doctors working in a tertiary hospital.

PubMed

Hoque, Muhammad Ehsanul

2016-06-01

In South Africa, HPV vaccination programme has been incorporated recently in the school health system. Since doctors are the most trusted people regarding health issues in general, their knowledge and attitudes regarding HPV infections and vaccination are very important for HPV vaccine program nationally. The objective of this study was to investigate factors contributing to recommendation of HPV vaccines to the patients. This was a quantitative cross-sectional study conducted among 320 doctors, using a self-administered anonymous questionnaire. All the doctors were aware of HPV and knew that HPV is transmitted sexually. Their overall level of knowledge regarding HPV infections and HPV vaccine was poor. But the majority intended to prescribe the vaccine to their patients. It was found that doctors who knew that HPV 6 and 11 are responsible for >90% of anogenital warts, their patients would comply with the counselling regarding HPV vaccination, and received sufficient information about HPV vaccination were 5.68, 4.91 and 4.46 times respectively more likely to recommend HPV vaccination to their patients, compared to their counterparts (p<0.05). There was a knowledge gap regarding HPV infection and HPV vaccine among the doctors.

Seroprevalence and Associated Factors of 9-Valent Human Papillomavirus (HPV) Types among Men in the Multinational HIM Study.

PubMed

Rahman, Shams; Pierce Campbell, Christine M; Rollison, Dana E; Wang, Wei; Waterboer, Tim; Michel, Angelika; Pawlita, Michael; Villa, Luisa L; Lazcano Ponce, Eduardo; Borenstein, Amy R; Giuliano, Anna R

2016-01-01

Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Recently a 9-valent HPV (9vHPV) prophylactic vaccine was licensed. Seroprevalence prior to vaccine dissemination is needed for monitoring vaccine effectiveness over time. Few studies have assessed the seroprevalence of 9vHPV types in men. To investigate the seroprevalence of 9vHPV vaccine types and associated risk factors among men residing in Brazil, Mexico, and the United States. Six hundred men were randomly selected from the HPV Infection in Men (HIM) Study. Archived serum specimens collected at enrollment were tested for antibodies against nine HPV types (6, 11, 16, 18, 31, 33, 45, 52 and 58) using a glutathione S-transferase (GST) L1-based multiplex serologic assay. Socio-demographic, lifestyle and sexual behavior data at enrollment were collected through a questionnaire. Binomial proportions were used to estimate seroprevalence and logistic regression was used to examine factors associated with seropositivity of type-specific and grouped (i.e. 9vHPV, high-risk 9vHPV, low risk 9vHPV, and five-additional) HPV types. Overall, 28.3% of men were seropositive for at least one of the 9vHPV vaccine types, 14.0% for at least one of the seven high-risk types (16, 18, 31, 33, 45, 52 and 58) and 11.2% for at least one of the five high-risk types (31, 33, 45, 52 and 58) not included in the quadrivalent HPV vaccine, and 17.4% for at least one of the low-risk types (6/11). In multivariate analyses, odds ratios adjusted (AOR) for country of residence, age, marital status, smoking, number of anal sex lifetime partners, compared to men with no anal sex lifetime partners, men with ≥2 partners were more likely to be seropositive for grouped HPV [(9vHPV: AOR 2.52; 95% confidence interval (CI) 1.40-4.54), (high-risk 9vHPV: AOR 2.18; 95%CI: 1.05-4.50) and (low-risk 9vHPV: AOR 2.12; 95%CI: 1.12-4.03)], and individual HPV types 6, 16, 33 and 58 with AORs ranging from 2.19 to 7.36. Compared to men aged 18-30 years, men older than 30 years were significantly more likely to be seropositive for any high-risk 9vHPV, in addition to individual types 18 and 45; and compared to never smokers, current smokers were more likely to be seropositive to 9vHPV, low-risk 9vHPV and HPV 6. In contrast, married men were less likely to be seropositive to any high-risk 9vHPV and individual HPV types 18 and 31 when compared to single men. These data indicate that exposure to the nine HPV types included in the 9vHPV vaccine is common in men and that seropositivity to 9vHPV vaccine types is associated with older age and the lifetime number of anal sex partners. Nine valent HPV vaccination of males and females has the potential to prevent HPV related diseases and transmission in both sexes.

New Approaches to Immunotherapy for HPV Associated Cancers

PubMed Central

Bergot, Anne-Sophie; Kassianos, Andrew; Frazer, Ian H; Mittal, Deepak

2011-01-01

Cervical cancer is the second most common cancer of women worldwide and is the first cancer shown to be entirely induced by a virus, the human papillomavirus (HPV, major oncogenic genotypes HPV-16 and -18). Two recently developed prophylactic cervical cancer vaccines, using virus-like particles (VLP) technology, have the potential to prevent a large proportion of cervical cancer associated with HPV infection and to ensure long-term protection. However, prophylactic HPV vaccines do not have therapeutic effects against pre-existing HPV infections and do not prevent their progression to HPV-associated malignancy. In animal models, therapeutic vaccines for persisting HPV infection can eliminate transplantable tumors expressing HPV antigens, but are of limited efficacy in inducing rejection of skin grafts expressing the same antigens. In humans, clinical trials have reported successful immunotherapy of HPV lesions, providing hope and further interest. This review discusses possible new approaches to immunotherapy for HPV associated cancer, based on recent advances in our knowledge of the immunobiology of HPV infection, of epithelial immunology and of immunoregulation, with a brief overview on previous and current HPV vaccine clinical trials. PMID:24212964

9-Valent HPV vaccine for cancers, pre-cancers and genital warts related to HPV.

PubMed

Pitisuttithum, Punnee; Velicer, Christine; Luxembourg, Alain

2015-01-01

Human papillomavirus (HPV) is the causative agent of nearly all cervical cancer cases as well as a substantial proportion of anal, vulvar, vaginal, penile and oropharyngeal cancers, making it responsible for approximately 5% of the global cancer burden. The first-generation HPV vaccines that is, quadrivalent HPV type 6/11/16/18 vaccine and bivalent HPV type 16/18 vaccine were licensed in 2006 and 2007, respectively. A second-generation 9-valent HPV type 6/11/16/18/31/33/45/52/58 vaccine with broader cancer coverage was initiated even before the first vaccines were approved. By preventing HPV infection and disease due to HPV31/33/45/52/58, the 9vHPV vaccine has the potential to increase prevention of cervical cancer from 70 to 90%. In addition, the 9vHPV vaccine has the potential to prevent 85-95% of HPV-related vulvar, vaginal and anal cancers. Overall, the 9vHPV vaccine addresses a significant unmet medical need, although further health economics and implementation research is needed.

Human papillomavirus-16 is the predominant type etiologically involved in penile squamous cell carcinoma.

PubMed

Heideman, Daniëlle A M; Waterboer, Tim; Pawlita, Michael; Delis-van Diemen, Pien; Nindl, Ingo; Leijte, Joost A; Bonfrer, Johannes M G; Horenblas, Simon; Meijer, Chris J L M; Snijders, Peter J F

2007-10-10

Human papillomavirus (HPV) infections are suggested to be involved in the development of penile squamous cell carcinoma (SCC), but comprehensive studies to define the association are limited. Therefore, we performed molecular and serologic analyses for a broad spectrum of HPV types on a large series of 83 penile SCCs, and we compared serological findings to those of age-matched male controls (N = 83). Penile SCCs were subjected to detection and typing assays for mucosal and cutaneous HPVs and to subsequent, type-specific viral load and viral gene expression assays. Sera of patients and of controls were analyzed for type-specific mucosal and cutaneous HPV L1, E6, and/or E7 antibodies using bead-based, multiplex serology. HPV DNA of mucosal and/or cutaneous types was found in 46 of 83 (55%) penile SCCs. HPV16 was the predominant type, appearing in 24 (52%) of 46 of penile SCCs. The majority of HPV16 DNA-positive SCCs (18 of 24; 75%) demonstrated E6 transcriptional activity and a high viral load. Additionally, HPV16 molecular findings were strongly associated with HPV16 L1-, E6-, and E7-antibody seropositivity. Furthermore, serologic case-control analyses demonstrated that, in addition to the association of HPV16 with penile SCC, seropositivity against any HPV type was significantly more common in patients compared with in controls. HPV18 and HPV6 seropositivity were associated with HPV16-negative SCCs but were not correlated to molecular findings. HPV16 is the main HPV type etiologically involved in the development of penile SCC. Although individuals who develop penile SCC show a greater prior exposure to a broad spectrum of HPV types, insufficient evidence was found to claim a role for HPV types other than HPV16 in penile carcinogenesis.

Multiple HPV genotype infection impact on invasive cervical cancer presentation and survival

PubMed Central

Martins, Toni Ricardo; Mendoza Lopez, Rossana V.; Sadalla, José Carlos; de Carvalho, João Paulo Mancusi; Baracat, Edmund Chada

2017-01-01

Background Invasive cervical cancer (ICC) is the third most common malignant neoplasm affecting Brazilian women. Little is known about the impact of specific HPV genotypes in the prognosis of ICC. We hypothesized that HPV genotype would impact ICC clinical presentation and survival. Methods Women diagnosed with ICC at the Instituto do Câncer do Estado de São Paulo (ICESP) between May 2008 and June 2012 were included in the study and were followed until December 2015. HPV genotype was detected from formalin-fixed paraffin-embedded (FFPE) tumor tissue samples using Onclarity™ system (BD Viper™ LT automated system). Results 292 patients aged 50±14 years were analyzed. HPVDNA was detected in 84% of patients. The HPV genotypes studied were: HPV16 (64%), HPV18 (10%), HPV33-58 (7%), HPV45 (5%), HPV31 (4%) and other high-risk HPV genotypes (11%). HPV genotypes showed different distributions regarding histological type and clinical stage. Patients were followed for 35±21 months. The overall survival at 5 years after diagnosis of cervical cancer was 54%. Age, clinical staging, histological type and multiple HPV genotypes infection detected in the same tumor specimen were associated with poorer overall survival on multivariate Cox proportional hazard analysis (p<0.05). No specific HPV genotype affected survival. Conclusion Multiple HPV genotype infection was associated with poorer ICC survival in our study, compared with single genotype infection. HPV genotyping from FFPE tumor tissue using an automated assay such as the Onclarity BD™ assay provides a simpler alternative for routine clinical use. Impact This is the largest study employing an automated HPV genotyping assay using FFPE of ICC. Multiple HPV genotype infection adversely influenced survival. PMID:28829791

Parents' Knowledge, Risk Perception and Willingness to Allow Young Males to Receive Human Papillomavirus (HPV) Vaccines in Uganda

PubMed Central

Muhwezi, Wilson Winstons; Banura, Cecily; Turiho, Andrew Kampikaho; Mirembe, Florence

2014-01-01

The Ministry of Health in Uganda in collaboration with the Program for Appropriate Technology for Health (PATH) supported by Bill and Melinda Gates Foundation in 2008–2009 vaccinated approximately 10,000 girls with the bivalent humanpapilloma virus (HPV) vaccine. We assessed parent's knowledge, risk perception and willingness to allow son(s) to receive HPV vaccines in future through a cross-sectional survey of secondary school boys aged 10–23 years in 4 districts. 377 questionnaires were distributed per district and 870 were used in analysis. Parents that had ever heard about cervical cancer and HPV vaccines; those who would allow daughter(s) to be given the vaccine and those who thought that HPV infection was associated with genital warts were more willing to allow son(s) to receive the HPV vaccine. Unwilling parents considered HPV vaccination of boys unimportant (p = 0.003), believed that only females should receive the vaccine (p = 0.006), thought their son(s) couldn't contract HPV (p = 0.010), didn't know about HPV sexual transmissibility (p = 0.002), knew that males could not acquire HPV (p = 0.000) and never believed that the HPV vaccines could protect against HPV (p = 0.000). Acceptance of HPV vaccination of daughters and likelihood of recommending HPV vaccines to son(s) of friends and relatives predicted parental willingness to allow sons to receive HPV vaccines. Probable HPV vaccination of boys is a viable complement to that of girls. Successfulness of HPV vaccination relies on parental acceptability and sustained sensitization about usefulness of HPV vaccines even for boys is vital. PMID:25203053

[Epidemiology and characterization of high-risk genotypes of human Papillomavirus in a population of sexually active adolescents in Ouagadougou].

PubMed

Ouédraogo, C M R; Rahimy, R M L; Zohoncon, T M; Djigma, F W; Yonli, A T; Ouermi, D; Sanni, A; Lankoande, J; Simpore, J

2015-10-01

This cross-sectional study was to determine the prevalence and characterization of high-risk HPV genotypes circulating among adolescents in Ouagadougou. From September to December 2013, 200 adolescents recruited from a youth counseling center have voluntarily accepted a swab of the endocervical canal. The identification of the genotypes of the human Papillomavirus (HPV) was performed by real-time polymerase chain reaction technique. The mean age of adolescents was 18.7±0.7 years and 83/200 adolescents were positive for at least one high-risk genotype HPV a prevalence of 41.5%. Twelve genotypes corresponding to 136 infections were characterized: HPV 52 (22.8%), HPV 59 (14.0%), HPV 39 (13.2%), HPV 35 (10.3%), HPV 51 (10.3%), HPV 56 (8.8%), HPV 16 (5.2%), HPV 18 (5.2%), HPV 58 (4.4%), HPV 31 (3.6%), HPV 45 (1.5%), HPV 33 (0.7%). Multiple infections (2-5 virus) statistically associated with age (p=0.0318) was detected in 42.2% of infected females. If the number of sexual partners was statistically associated with the porting of HPV (OR=2.18; 95% CI=1.17 to 4.09), early sexual intercourse and the recent change of sexual partner were not (p>0,05) CONCLUSION: The prevalence of carriage of HPV in this study is high, as described in young people at the start of sexual activity. Identified genotypes are different from those targeted by prophylactic vaccines currently available. A larger study to map genotypes of high-risk HPV circulating in West Africa is necessary for a suitable vaccine. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Comparison of cytology, HPV DNA testing and HPV 16/18 genotyping alone or combined targeting to the more balanced methodology for cervical cancer screening.

PubMed

Chatzistamatiou, Kimon; Moysiadis, Theodoros; Moschaki, Viktoria; Panteleris, Nikolaos; Agorastos, Theodoros

2016-07-01

The objective of the present study was to identify the most effective cervical cancer screening algorithm incorporating different combinations of cytology, HPV testing and genotyping. Women 25-55years old recruited for the "HERMES" (HEllenic Real life Multicentric cErvical Screening) study were screened in terms of cytology and high-risk (hr) HPV testing with HPV 16/18 genotyping. Women positive for cytology or/and hrHPV were referred for colposcopy, biopsy and treatment. Ten screening algorithms based on different combinations of cytology, HPV testing and HPV 16/18 genotyping were investigated in terms of diagnostic accuracy. Three clusters of algorithms were formed according to the balance between effectiveness and harm caused by screening. The cluster showing the best balance included two algorithms based on co-testing and two based on HPV primary screening with HPV 16/18 genotyping. Among these, hrHPV testing with HPV 16/18 genotyping and reflex cytology (atypical squamous cells of undetermined significance - ASCUS threshold) presented the optimal combination of sensitivity (82.9%) and specificity relative to cytology alone (0.99) with 1.26 false positive rate relative to cytology alone. HPV testing with HPV 16/18 genotyping, referring HPV 16/18 positive women directly to colposcopy, and hrHPV (non 16/18) positive women to reflex cytology (ASCUS threshold), as a triage method to colposcopy, reflects the best equilibrium between screening effectiveness and harm. Algorithms, based on cytology as initial screening method, on co-testing or HPV primary without genotyping, and on HPV primary with genotyping but without cytology triage, are not supported according to the present analysis. Copyright © 2016 Elsevier Inc. All rights reserved.

Patients with integrated HPV16 in head and neck cancer show poor survival.

PubMed

Nulton, Tara J; Kim, Nak-Kyeong; DiNardo, Laurence J; Morgan, Iain M; Windle, Brad

2018-05-01

We previously reported identifying three categories of HPV16-positive head and neck tumors based on The Cancer Genome Atlas (TCGA) RNA and DNA sequence data. Category 1 had truly integrated HPV16 genomes, category 2 had simple episomal genomes, and category 3 had novel episomes that were a hybrid between viral and human DNA. Using our categorization, we investigated in this study survival of patients with integrated HPV16 tumors versus patients with episomal HPV16 tumors. The TCGA RNA-Seq sequence reads were used to quantify HPV E2 and E7 gene expression, which was used as a marker for HPV integration. The results demonstrate that integration is associated with poor survival; those patients with integrated HPV tumors fared no better than non-HPV tumors in their five-year survival. Integrated HPV in tumors was found strikingly to be prevalent in patients born earlier while episomal HPV was prevalent in patients born later. We also observed a fairly constant incidence of all HPV forms among head and neck cancer patients over the last eight years of this study (2006-2013). We propose our characterization of HPV integrated and episomal state is more accurate than previous studies that may have mischaracterized the hybrid HPV-human DNA episomes as integrated. The state of integrated HPV is associated with a poor clinical outcome. Results suggest that the incidence of integrated HPV among all HPV forms peaked and is decreasing. We discuss the importance of our findings for the management of HPV positive head and neck cancer. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Human papillomavirus types 16 and 18 DNA load in relation to coexistence of other types, particularly those in the same species.

PubMed

Xi, Long Fu; Edelstein, Zoe R; Meyers, Craig; Ho, Jesse; Cherne, Stephen L; Schiffman, Mark

2009-09-01

Infection with multiple human papillomavirus (HPV) types is common. However, it is unknown whether viral DNA load is related to the coexistence of other types. Study subjects were 802 and 303 women who were positive for HPV16 and HPV18, respectively, at enrollment into the Atypical Squamous Cells of Undetermined Significance and Low-Grade Squamous Intraepithelial Lesion Triage Study. HPV16 and HPV18 E7 copies per nanogram of cellular DNA in cervical swab samples were measured by real-time PCR in triplicate. Concurrent coinfection was common in this population of women with minor cervical lesions; multiple HPV types were detected in 573 (71.4%) of 802 HPV16-positive women and 227 (74.9%) of 303 HPV18-positive women. The adjusted odds ratio associating coinfection with per 1 log unit increase in HPV16 DNA load was 0.78 (95% confidence interval, 0.68-0.89); it was 0.64 (95% confidence interval, 0.52-0.79) for a similar analysis of HPV18 DNA load. Women with, compared with without, coinfection of A9 species types possessed a significantly lower HPV16 DNA load (P < 0.001), whereas women with, compared with without, coinfection of A7 species types possessed a significantly lower HPV18 DNA load (P = 0.001). A trend of decrease in HPV16 DNA load with increasing number of the coexisting non-HPV16 A9 species types was statistically significant (P(trend) = 0.001). Coinfection with other types was associated with lower HPV16 and HPV18 DNA load. The extent of reduction was correlated to phylogenetic distance of the coexisting types to HPV16 and HPV18, respectively.

Human papillomavirus detection with genotyping by the cobas and Aptima assays: Significant differences in HPV 16 detection?

PubMed

Chorny, Joseph A; Frye, Teresa C; Fisher, Beth L; Remmers, Carol L

2018-03-23

The primary high-risk human papillomavirus (hrHPV) assays in the United States are the cobas (Roche) and the Aptima (Hologic). The cobas assay detects hrHPV by DNA analysis while the Aptima detects messenger RNA (mRNA) oncogenic transcripts. As the Aptima assay identifies oncogenic expression, it should have a lower rate of hrHPV and genotype detection. The Kaiser Permanente Regional Reference Laboratory in Denver, Colorado changed its hrHPV assay from the cobas to the Aptima assay. The rates of hrHPV detection and genotyping were compared over successive six-month periods. The overall hrHPV detection rates by the two platforms were similar (9.5% versus 9.1%) and not statistically different. For genotyping, the HPV 16 rate by the cobas was 1.6% and by the Aptima it was 1.1%. These differences were statistically different with the Aptima detecting nearly one-third less HPV 16 infections. With the HPV 18 and HPV 18/45, there was a slightly higher detection rate of HPV 18/45 by the Aptima platform (0.5% versus 0.9%) and this was statistically significant. While HPV 16 represents a low percentage of hrHPV infections, it was detected significantly less by the Aptima assay compared to the cobas assay. This has been previously reported, although not highlighted. Given the test methodologies, one would expect the Aptima to detect less HPV 16. This difference appears to be mainly due to a significantly increased number of non-oncogenic HPV 16 infections detected by the cobas test as there were no differences in HPV 16 detection rates in the high-grade squamous intraepithelial lesions indicating that the two tests have similar sensitivities for oncogenic HPV 16. © 2018 Wiley Periodicals, Inc.

Carcinogenic HPV prevalence and age-specific type distribution in 40,382 women with normal cervical cytology, ASCUS/LSIL, HSIL, or cervical cancer: what is the potential for prevention?

PubMed

Kjær, Susanne K; Munk, Christian; Junge, Jette; Iftner, Thomas

2014-02-01

Assessment of the prevaccination type-specific prevalence of human papillomavirus (HPV) in the general population is important for the prediction of the impact of HPV vaccination. We collected consecutively residual specimens from liquid-based cytology samples from 40,382 women from the general population in Copenhagen, Denmark, during 2002-2005. All samples were tested for high-risk HPV using the Hybrid Capture 2 technique, and genotyping was done using LiPa (Innogenetics). Through linkage with the Pathology Data Bank, we obtained information on the cytology result, and histology if any, on all women. The participants were 14-95 years of age (median age 37 years) at enrollment. The overall prevalence of HR HPV was 20.6 % ranging from 46.0 % in 20-23-year-old women to 5.7 % in women 65 years or older. Independently of cytology/histology, HPV16 was the most prevalent type. For virtually all HPV types, the occurrence of CIN3+ was higher when the specific HPV type was present together with HPV16 than it was together with other high-risk HPV types than HPV16 or if the HPV type occurred as a single infection. The prevalence of HPV16 and/or HPV18 was 74 % in cervical cancer and the corresponding prevalence of HPV16/18/31/33/45/52/58 was 89 %. This study forms a valuable starting point for monitoring the effect of HPV vaccination in Denmark. In addition, the particular carcinogenic role of HPV16 and 18 is confirmed and may support a role of genotyping for HPV16 and 18 in cervical cancer screening.

Analysis of Human Papillomavirus Infection in 16,320 Patients From a Gynecology Clinic in Central South China.

PubMed

Xiao, Song S; Fan, Jie L; He, Si L; Li, Yue R; Wang, Lu Y; Yu, Ke N; Deng, Xin L; Xue, Min

2016-10-01

This study aimed to investigate the relationship between persistent human papillomavirus (HPV) infection and cervical lesion. Clinical data of 16,320 patients who visited our clinic between January 2009 and December 2013 were collected. Retrospective analysis was performed to analyze the overall HPV infection and compare the infection rates of different subtypes among different age groups, to reveal the relationship between persistent HPV infection and cervical cytology. The overall prevalence of HPV was 26.54%. The most common genotypes were HPV 52, HPV 16, HPV 58, CP8304, and HPV 53. The highest overall high-risk HPV prevalence was found in women older than 60 years, and the lowest prevalence was found in women between the ages of 30 and 39 years. There was no significant difference in low-risk HPV prevalence among different age groups (p = .693). The HPV clearance rate after 1 year among those with initial positive test was 87.65%. The constituent ratios of high- or low-risk HPV subtypes were not significantly different (p = .545) between nonpersistent-positive and persistent-positive (PP) groups. Conversely, the constituent ratios of singe- or multi-type HPV infection were significantly different (p < .05) between these 2 groups. The most common subtypes in PP group were HPV 16, 52, 58, CP8304, and 33. The occurrence rates of atypical squamous cells of undetermined significance, high-grade squamous intraepithelial lesion, and squamous cell carcinoma in the PP group significantly increased (p < .05). Persistent HPV infections are mainly caused by multiple types of HPV and high-risk HPV. Our region should particularly pay attention to the prevention and treatment of HPV 16, 52, and 58.

Type-Specific Human Papillomavirus Distribution in Invasive Squamous Cervical Carcinomas in Tunisia and Vaccine Impact.

PubMed

Ennaifer, Emna; Salhi, Faten; Laassili, Thalja; Fehri, Emna; Ben Alaya, Nissaf; Guizani, Ikram; Boubaker, Samir

2015-01-01

High risk human papillomaviruses (HPVs) are the leading cause of cervical cancer (CC) and Pap smear screening has not been successful in preventing CC in Tunisia. HPV vaccination that targets HPV16 and 18 offers a new efficient prevention tool. Identification of HPV types in CC is thus essential to determine the impact of HPV vaccine implementation. The aim of this study is to provide specific data from Tunisia. A total of 89 histological confirmed paraffin embedded samples isolated from patients with CC diagnosed between 2001 and 2011 were collected from five medical centres from Northern and Southern Tunisia. HPV DNA was detected using a nested PCR (MY09/MY11-GP5+/GP6+) and genotyping was assessed using a reverse blot line hybridisation assay that enables the detection of 32 HPV types. HPV DNA was detected in all samples. Twelve high risk types were detected; HPV16 and/or 18 were predominant, accounting together for 92.1% of all the CC cases (HPV16: 83.1%). Single infections accounted for 48.8% of the cases and were mostly linked to HPV 16 (32.6%) and less frequently to HPV 18 (2.4%). The other high risk HPV single infections were linked to HPV 35 (4.6%), 45 (4.6%), 58 (2.3%) and 59 (2.3%). Multiple infections with mixing of 2 to 4 genotypes predominately featrued HPV16 and/or 18 with HPV 35 and 45 (96.6 %) and less frequently with HPV 59, 40, 66, 73 and 58. There was no statistically significant variation in the relative distribution of HPV types with age. These results strongly indicate that prophylactic HPV vaccines can have a major impact in preventing CC in Tunisia.

Comparison of the performance in detection of HPV infections between the high-risk HPV genotyping real time PCR and the PCR-reverse dot blot assays.

PubMed

Zhang, Lahong; Dai, Yibei; Chen, Jiahuan; Hong, Liquan; Liu, Yuhua; Ke, Qiang; Chen, Yiwen; Cai, Chengsong; Liu, Xia; Chen, Zhaojun

2018-01-01

A new multiplex real-time PCR assay, the high-risk HPV genotyping real time PCR assay (HR HPV RT-PCR), has been developed to detect 15 high-risk HPV types with respective viral loads. In this report, a total of 684 cervical specimens from women diagnosed with vaginitis were assessed by the HR HPV RT-PCR and the PCR reaction and reverse dot blot (PCR-RDB) assays, using a PCR-sequencing method as a reference standard. A total coincidence of 97.7% between the HR HPV RT PCR and the PCR-RDB assays was determined with a Kappa value of 0.953. The HR HPV RT PCR assay had sensitivity, specificity, and concordance rates (accuracy) of 99.7%, 99.7%, and 99.7%, respectively, as confirmed by PCR-sequencing, while the PCR-RDB assay had respective rates of 98.8%, 97.1%, and 98.0%. The overall rate of HPV infection, determined by PCR-sequencing, in women diagnosed with vaginitis was 49.85%, including 36.26% of single infection and 13.6% of multiple infections. The most common infections among the 15 high-risk HPV types in women diagnosed with vaginitis were HPV-52, HPV-16, and HPV-58, with a total detection rate of 10.23%, 7.75%, and 5.85%, respectively. We conclude that the HR HPV RT PCR assay exhibits better clinical performance than the PCR-RDB assay, and is an ideal alternative method for HPV genotyping. In addition, the HR HPV RT PCR assay provides HPV DNA viral loads, and could serve as a quantitative marker in the diagnosis and treatment of single and multiple HPV infections. © 2017 Wiley Periodicals, Inc.

Study of Far—Field Directivity Pattern for Linear Arrays

NASA Astrophysics Data System (ADS)

Ana-Maria, Chiselev; Luminita, Moraru; Laura, Onose

2011-10-01

A model to calculate directivity pattern in far field is developed in this paper. Based on this model, the three-dimensional beam pattern is introduced and analyzed in order to investigate geometric parameters of linear arrays and their influences on the directivity pattern. Simulations in azimuthal plane are made to highlight the influence of transducers parameters, including number of elements and inter-element spacing. It is true that these parameters are important factors that influence the directivity pattern and the appearance of side-lobes for linear arrays.

Demographic and High-Risk Behaviors associated with HPV and HPV Vaccine Awareness among Persons Aged 15-74 Years in Puerto Rico.

PubMed

Reyes, Juan Carlos; Sánchez-Díaz, Carola T; Tortolero-Luna, Guillermo; Colón, Hector M; Ortiz, Ana Patricia

2015-12-01

Studies of human papillomavirus (HPV) awareness in Puerto Rico (PR) are limited and are of interest given low HPV vaccine uptake in this population. This cross-sectional study aimed to determine factors associated to HPV and HPV vaccine awareness among persons aged 15-74 years living in Puerto Rico. We analysed data from a sub-sample of 1,476 men and women who participated in a 2008 population-based island-wide household survey and who completed an HPV module. Multivariate logistic regression models were used to examine factors associated with HPV and HPV vaccine awareness. Overall, 37.2% of participants had heard about HPV and 33.4% had heard of the vaccine. Multivariate logistic regression showed that women were more likely to have heard of HPV (OR adjusted: 4.54; 95% CI=3.45, 5.98) or of the HPV vaccine (OR adjusted: 6.15; 95% CI=4.50, 8.40) as compared to men. HPV awareness was also lower among older adults, persons with lower income and with lower educational attainment, those without children and smokers (p < 0.05). In 2008, two years after the introduction of the first HPV vaccine in PR and the US, public awareness about HPV infection and the HPV vaccine was lower in Hispanics in PR as compared to other populations. Identified high-risk populations should be targeted in preventive care strategies. Future efforts should increase HPV knowledge and vaccine use in this population in order to maximize the impact of vaccination programs.

Etiological role of human papillomavirus infection for inverted papilloma of the bladder.

PubMed

Shigehara, Kazuyoshi; Sasagawa, Toshiyuki; Doorbar, John; Kawaguchi, Shohei; Kobori, Yoshitomo; Nakashima, Takao; Shimamura, Masayoshi; Maeda, Yuji; Miyagi, Tohru; Kitagawa, Yasuhide; Kadono, Yoshifumi; Konaka, Hiroyuki; Mizokami, Atsushi; Koh, Eitetsu; Namiki, Mikio

2011-02-01

The status of human papillomavirus (HPV) infection in urothelial inverted papilloma was examined in the present study. Formalin-fixed and paraffin-embedded tissues from eight cases of inverted papilloma of the bladder were studied. The presence of HPV-DNA was examined by modified GP5/6+PCR using archival tissue sections by microdissection. HPV genotype was determined with a Hybri-Max HPV genotyping kit. Immunohistochemical analysis for p16-INK4a, mcm7, HPV-E4, and L1, and in situ hybridization for the HPV genome were performed. HPV was detected in seven of eight cases (87.5%) of inverted papilloma. Three cases were diagnosed as inverted papilloma with atypia, while the remaining five were typical cases. HPV-18 was detected in two cases, including one inverted papilloma with atypia, and HPV-16 was detected in four cases, including one inverted papilloma with atypia. Multiple HPV type infection was detected in one typical case and one atypical case. High-risk HPV was present in all HPV-positive cases. Cellular proteins, p16-INK4a and mcm7, which are surrogate markers for HPV-E7 expression, were detected in all HPV-positive cases, and their levels were higher in inverted papilloma with atypia than in typical cases. In contrast, HPV-E4 and L1, which are markers for HPV propagation, were observed in some parts of the typical inverted papilloma tissue. High-risk HPV infection may be one of the causes of urothelial inverted papilloma, and inverted papilloma with atypia may have malignant potential. 2010 Wiley-Liss, Inc.

Identification of human papillomavirus (HPV) 16 DNA integration and the ensuing patterns of methylation in HPV-associated head and neck squamous cell carcinoma cell lines.

PubMed

Hatano, Takashi; Sano, Daisuke; Takahashi, Hideaki; Hyakusoku, Hiroshi; Isono, Yasuhiro; Shimada, Shoko; Sawakuma, Kae; Takada, Kentaro; Oikawa, Ritsuko; Watanabe, Yoshiyuki; Yamamoto, Hiroyuki; Itoh, Fumio; Myers, Jeffrey N; Oridate, Nobuhiko

2017-04-01

Recent studies showed that human papillomavirus (HPV) integration contributes to the genomic instability seen in HPV-associated head and neck squamous cell carcinoma (HPV-HNSCC). However, the epigenetic alterations induced after HPV integration remains unclear. To identify the molecular details of HPV16 DNA integration and the ensuing patterns of methylation in HNSCC, we performed next-generation sequencing using a target-enrichment method for the effective identification of HPV16 integration breakpoints as well as the characterization of genomic sequences adjacent to HPV16 integration breakpoints with three HPV16-related HNSCC cell lines. The DNA methylation levels of the integrated HPV16 genome and that of the adjacent human genome were also analyzed by bisulfite pyrosequencing. We found various integration loci, including novel integration sites. Integration loci were located predominantly in the intergenic region, with a significant enrichment of the microhomologous sequences between the human and HPV16 genomes at the integration breakpoints. Furthermore, various levels of methylation within both the human genome and the integrated HPV genome at the integration breakpoints in each integrant were observed. Allele-specific methylation analysis suggested that the HPV16 integrants remained hypomethylated when the flanking host genome was hypomethylated. After integration into highly methylated human genome regions, however, the HPV16 DNA became methylated. In conclusion, we found novel integration sites and methylation patterns in HPV-HNSCC using our unique method. These findings may provide insights into understanding of viral integration mechanism and virus-associated carcinogenesis of HPV-HNSCC. © 2016 UICC.

Smoking and human papillomavirus (HPV) infection in the HPV in Men (HIM) study.

PubMed

Schabath, Matthew B; Villa, Luisa L; Lazcano-Ponce, Eduardo; Salmerón, Jorge; Quiterio, Manuel; Giuliano, Anna R

2012-01-01

The influence of smoking on the natural history of HPV infection in men is not well understood. Smoking could influence the incidence and persistence of HPV infections by suppressing local immune function, increased cellular proliferation, upregulated proinflammatory factors, or induced host DNA damage resulting in increased susceptibility to infection. The purpose of this analysis is to assess prevalent HPV infections by smoking status in men, and to determine baseline risk of HPV infection associated with smoking. The HPV in Men (HIM) study is a multinational prospective study of the natural history of HPV infections in men. Samples from the coronal sulcus, glans penis, shaft, and scrotum were combined for HPV DNA testing. Multivariable logistic regression was used to assess the association between smoking and any-, oncogenic-, and nononcogenic HPV infections. Our analyses revealed that current smoking was associated with an increased risk of any HPV infection (OR = 1.19; 95% CI: 1.01-1.41) and oncogenic HPV infection (OR = 1.24; 95% CI: 1.05-1.47). However, the association between smoking and any HPV infection (OR = 1.35; 95% CI: 1.05-1.73) and oncogenic HPV infection (OR = 1.46; 95% CI: 1.11-1.92) was only evident among men reporting fewer lifetime sexual partners. These results suggest that current smokers with the fewest number of sexual partners are associated with an increased risk for oncogenic HPV infection. The relationship between smoking and HPV infection remains understudied in men; these data shed new light on the interplay between smoking, sexual activity, and risk of HPV infection.

Revisiting knowledge, attitudes and practice (KAP) on human papillomavirus (HPV) vaccination among female university students in Hong Kong.

PubMed

Leung, Jonathan Tin Chi; Law, Chi-Kin

2018-04-03

Despite cervical cancer can be preventable by HPV vaccination, little is known on its associated factors among young females in Hong Kong. This study aimed to investigate the present situation regarding the self-reported knowledge, attitudes and practice (KAP) of Human Papillomavirus (HPV) vaccination and to examine their associated factors among female university students in Hong Kong. 195 respondents were recruited to complete a self-administered questionnaire from two local universities through convenience sampling. 8.2% respondents indicated that family doctors as sources of knowledge of HPV and HPV vaccination. 59.0% of the sample identified more than four knowledge items, 82.6% thought that HPV vaccines can effectively prevent cervical cancer and 47.2% received HPV vaccination. Regression analyses found those at older age, thought that they might be infected by HPV and received HPV would have a higher level of knowledge. Those who knew HPV is sexually transmitted, thought may be infected by HPV and received HPV vaccination would have positive attitude on HPV vaccination. Those at older ages, knew their university provided discounted vaccination for female students, and were not afraid of the side effects were associated with HPV vaccination. Family doctors should take a more prominent role in disseminating accurate and precise information. Advocacies should be emphasised on the risk of HPV as a sexually transmitted disease and the availability of discounted and safe HPV vaccines in tertiary educational institutions to increase the uptake rate of HPV vaccines for first-year and non-health major university students.

High prevalence and incidence of human papillomavirus in a cohort of healthy young African female subjects

PubMed Central

Watson-Jones, Deborah; Baisley, Kathy; Brown, Joelle; Kavishe, Bazil; Andreasen, Aura; Changalucha, John; Mayaud, Philippe; Kapiga, Saidi; Gumodoka, Balthazar; Hayes, Richard J; de Sanjosé, Silvia

2013-01-01

Objectives We measured the prevalence and incidence of human papillomavirus (HPV) infection in young female subjects recruited for a safety and immunogenicity trial of the bivalent HPV-16/18 vaccine in Tanzania. Methods Healthy HIV negative female subjects aged 10–25 years were enrolled and randomised (2:1) to receive HPV-16/18 vaccine or placebo (Al(OH)3 control). At enrolment, if sexually active, genital specimens were collected for HPV DNA, other reproductive tract infections and cervical cytology. Subjects were followed to 12 months when HPV testing was repeated. Results In total 334 participants were enrolled; 221 and 113 in vaccine and control arms, respectively. At enrolment, 74% of 142 sexually active subjects had HPV infection of whom 69% had >1 genotype. Prevalent infections were HPV-45 (16%), HPV-53 (14%), HPV-16 (13%) and HPV-58 (13%). Only age was associated with prevalent HPV infection at enrolment. Among 23 girls who reported age at first sex as 1 year younger than their current age, 15 (65.2%) had HPV infection. Of 187 genotype-specific infections at enrolment, 51 (27%) were present at 12 months. Overall, 67% of 97 sexually active participants with results at enrolment and 12 months had a new HPV genotype at follow-up. Among HPV uninfected female subjects at enrolment, the incidence of any HPV infection was 76 per 100 person-years. Conclusions Among young women in Tanzania, HPV is highly prevalent and acquired soon after sexual debut. Early HPV vaccination is highly recommended in this population. PMID:23486859

Should I or shouldn't I: decision making, knowledge and behavioral effects of quadrivalent HPV vaccination in men who have sex with men.

PubMed

Thomas, Emily A; Goldstone, Stephen E

2011-01-10

Prior to FDA licensure in men, a surgical practice (SG) offered the quadrivalent HPV vaccine (qHPV) off-label to men who have sex with men (MSM). We administered a written or telephone survey to MSM to elicit drivers and barriers to vaccination, sexual behavior changes post-vaccination, and knowledge. 191 subjects enrolled: 68 refused qHPV, 71 received qHPV <1 year ago, and 52 received qHPV >1 year ago. History of HPV infection (86%, n=164) and level of HPV and qHPV knowledge were high, with a mean of 10.8 of 13 knowledge questions correct. Ninety-seven percent of participants understood that qHPV does not cure present infection or disease. MSM refused qHPV for reasons including cost and not FDA approved; prevention of future HPV infection was the paramount driver for immunization. Vaccination did not affect sexual behavior. Copyright © 2010 Elsevier Ltd. All rights reserved.

The DNA damage response activates HPV16 late gene expression at the level of RNA processing.

PubMed

Nilsson, Kersti; Wu, Chengjun; Kajitani, Naoko; Yu, Haoran; Tsimtsirakis, Efthymios; Gong, Lijing; Winquist, Ellenor B; Glahder, Jacob; Ekblad, Lars; Wennerberg, Johan; Schwartz, Stefan

2018-06-01

We show that the alkylating cancer drug melphalan activated the DNA damage response and induced human papillomavirus type 16 (HPV16) late gene expression in an ATM- and Chk1/2-dependent manner. Activation of HPV16 late gene expression included inhibition of the HPV16 early polyadenylation signal that resulted in read-through into the late region of HPV16. This was followed by activation of the exclusively late, HPV16 splice sites SD3632 and SA5639 and production of spliced late L1 mRNAs. Altered HPV16 mRNA processing was paralleled by increased association of phosphorylated BRCA1, BARD1, BCLAF1 and TRAP150 with HPV16 DNA, and increased association of RNA processing factors U2AF65 and hnRNP C with HPV16 mRNAs. These RNA processing factors inhibited HPV16 early polyadenylation and enhanced HPV16 late mRNA splicing, thereby activating HPV16 late gene expression.

An ANSERLIN array for mobile satellite applications

NASA Technical Reports Server (NTRS)

Colomb, F. Y.; Kunkee, D. B.; Mayes, P. E.; Smith, D. W.; Jamnejad, V.

1990-01-01

Design, analysis, construction, and test of linear arrays of ANSERLIN (annular sector, radiating line) elements are reported and discussed. Due to feeding simplicity and easy construction as well as good CP performance, a planar array composed of a number of such linear arrays each producing a shaped beam tilted in elevation, is a good candidate as a vehicle-mounted mechanically steered antenna for mobile satellite applications. A single level construction technique was developed that makes this type of array very cost competitive with other low-profile arrays. An asymmetric 19.5 inch long four-element array was fabricated and tested with reasonable performance. A smaller five-element symmetric array (16 inch long) was also designed and tested capable of operating in either sense of circular polarization. Efforts were made to successfully reduce this effect.

Temporal Nodal Regression and Regional Control After Primary Radiation Therapy for N2-N3 Head-and-Neck Cancer Stratified by HPV Status

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Shao Hui; O'Sullivan, Brian; Xu, Wei

Purpose: To compare the temporal lymph node (LN) regression and regional control (RC) after primary chemoradiation therapy/radiation therapy in human papillomavirus-related [HPV(+)] versus human papillomavirus-unrelated [HPV(−)] head-and-neck cancer (HNC). Methods and Materials: All cases of N2-N3 HNC treated with radiation therapy/chemoradiation therapy between 2003 and 2009 were reviewed. Human papillomavirus status was ascertained by p16 staining on all available oropharyngeal cancers. Larynx/hypopharynx cancers were considered HPV(−). Initial radiologic complete nodal response (CR) (≤1.0 cm 8-12 weeks after treatment), ultimate LN resolution, and RC were compared between HPV(+) and HPV(−) HNC. Multivariate analysis identified outcome predictors. Results: A total of 257more » HPV(+) and 236 HPV(−) HNCs were identified. The initial LN size was larger (mean, 2.9 cm vs 2.5 cm; P<.01) with a higher proportion of cystic LNs (38% vs 6%, P<.01) in HPV(+) versus HPV(−) HNC. CR was achieved is 125 HPV(+) HNCs (49%) and 129 HPV(−) HNCs (55%) (P=.18). The mean post treatment largest LN was 36% of the original size in the HPV(+) group and 41% in the HPV(−) group (P<.01). The actuarial LN resolution was similar in the HPV(+) and HPV(−) groups at 12 weeks (42% and 43%, respectively), but it was higher in the HPV(+) group than in the HPV(−) group at 36 weeks (90% vs 77%, P<.01). The median follow-up period was 3.6 years. The 3-year RC rate was higher in the HPV(−) CR cases versus non-CR cases (92% vs 63%, P<.01) but was not different in the HPV(+) CR cases versus non-CR cases (98% vs 92%, P=.14). On multivariate analysis, HPV(+) status predicted ultimate LN resolution (odds ratio, 1.4 [95% confidence interval, 1.1-1.7]; P<.01) and RC (hazard ratio, 0.3 [95% confidence interval 0.2-0.6]; P<.01). Conclusions: HPV(+) LNs involute more quickly than HPV(−) LNs but undergo a more prolonged process to eventual CR beyond the time of initial assessment at 8 to 12 weeks after treatment. Post radiation neck dissection is advisable for all non-CR HPV(−)/non-CR N3 HPV(+) cases, but it may be avoided for selected non-CR N2 HPV(+) cases with a significant LN involution if they can undergo continued imaging surveillance. The role of positron emission tomography for response assessment should be investigated.« less

Kinetic and HPV infection effects on cross-type neutralizing antibody and avidity responses induced by Cervarix®

PubMed Central

Kemp, Troy J.; Safaeian, Mahboobeh; Hildesheim, Allan; Pan, Yuanji; Penrose, Kerri J.; Porras, Carolina; Schiller, John T.; Lowy, Douglas R.; Herrero, Rolando; Pinto, Ligia A.

2012-01-01

Background We previously demonstrated that Cervarix® elicits antibody responses against vaccine-related types for which clinical efficacy was demonstrated (HPV-31 and -45). Here, we evaluated the kinetics of neutralization titers and avidity of Cervarix®-induced antibodies up to 36 months of follow-up in unexposed and HPV infected women. Methods A subset of women who participated in the Cost Rica HPV-16/18 Vaccine Trial had pre- and post-vaccination sera tested for antibody responses to HPV-16, -18, -31, -45, and -58 using a pseudovirion-based neutralization assay, and HPV-16 antibody avidity using an HPV-16 L1 VLP (virus-like particle)-based ELISA developed in our laboratory. Results In uninfected women, neutralizing antibody titers did not reach significance until after the 3rd dose for HPV-31 (month 12, p=0.009) and HPV-45 (month 12, p=0.003), but then persisted up to month 36 (HPV-31, p=0.01; HPV-45, p=0.002). Individuals infected with HPV-16 or HPV-31 at enrollment developed a significantly higher median antibody response to the corresponding HPV type after one dose, but there was not a difference between median titers after three doses compared to the HPV negative group. Median HPV-16 antibody avidity and titer increased over time up to month 12; however, the HPV-16 avidity did not correlate well with HPV-16 neutralizing antibody titers at each time point examined, except for month 6. The median avidity levels were higher in HPV-16 infected women at month 1 (p=0.04) and lower in HPV-16 infected women at month 12 (p=0.006) compared to the HPV negative women. Conclusions The persistence of cross-neutralization titers at month 36 suggests cross-reactive antibody responses are likely to persist long-term and are not influenced by infection status at enrollment. However, the weak correlation between avidity and neutralization titers emphasizes the need for examining avidity in efficacy studies to determine if high avidity antibodies play a critical role in protection against infection. PMID:23123024

Nationwide prevalence of human papillomavirus infection and viral genotype distribution in 37 cities in China.

PubMed

Wang, Rong; Guo, Xiao-Lei; Wisman, G Bea A; Schuuring, Ed; Wang, Wen-Feng; Zeng, Zheng-Yu; Zhu, Hong; Wu, Shang-Wei

2015-07-04

Type-specific high-risk HPV (hrHPV) infection is related to cervical carcinogenesis. The prevalence of hrHPV infection varies geographically, which might reflect the epidemiological characteristics of cervical cancer among different populations. To establish a foundation for HPV-based screening and vaccination programs in China, we investigated the most recent HPV prevalence and genotypic distributions in different female age groups and geographical regions in China. In 2012, a total of 120,772 liquid-based cytological samples from women enrolled for population- or employee-based cervical screening in 37 Chinese cities were obtained by the Laboratory of Molecular Infectious Diseases of Guangzhou KingMed. A total of 111,131 samples were tested by Hybrid Capture II and the other 9,641 were genotyped using the Tellgenplex™ HPV DNA Assay. The total positive rate for hrHPV was 21.07 %, which ranged from 18.42 % (Nanchang) to 31.94 % (Haikou) and varied by region. The regions of Nanchang, Changsha, Hangzhou, Chengdu, Fuzhou, Guangdong, and Guiyang could be considered the low prevalence regions. Age-specific prevalence showed a "two-peak" pattern, with the youngest age group (15-19 years) presenting the highest hrHPV infection rate (30.55 %), followed by a second peak for the 50-60-year-old group. Overall, the most prevalent genotypes were HPV16 (4.82 %) and HPV52 (4.52 %), followed by HPV58 (2.74 %). Two genotypes HPV6 (4.01 %) and HPV11 (2.29 %) were predominant in the low-risk HPV (lrHPV) type, while the mixed genotypes HPV16 + 52 and HPV52 + 58 were most common in women with multiple infections. This study shows that HPV infection in China has increased to the level of an "HPV-heavy-burden" zone in certain regions, with prevalence varying significantly among different ages and regions. Data from this study represent the most current survey of the nationwide prevalence of HPV infection in China, and can serve as valuable reference to guide nationwide cervical cancer screening and HPV vaccination programs.

Discrepant HPV/cytology cotesting results: Are there differences between cytology-negative versus HPV-negative cervical intraepithelial neoplasia?

PubMed

Tracht, Jessica M; Davis, Antoinette D; Fasciano, Danielle N; Eltoum, Isam-Eldin A

2017-10-01

The objective of this study was to compare cervical high-grade squamous intraepithelial lesions subcategorized as cervical intraepithelial neoplasia-3 (CIN-3)-positive after a negative cytology result but positive for high-risk human papillomavirus (HR-HPV) testing to those with a negative HR-HPV test but positive cytology (atypical squamous cells of undetermined significance [ASCUS]-positive/HPV-negative) and to assess reasons for discrepancies. The authors retrospectively analyzed women who underwent screening with cytology and HPV testing from 2010 through 2013. After a review of surgical specimens and cytology, discrepancies were classified as sampling or interpretation error. Clinical and pathologic findings were compared. In total, 15,173 women (age range, 25-95 years; 7.1% were aged < 30 years) underwent both HPV and cytologic testing, and 1184 (8.4%) underwent biopsy. Cytology was positive in 19.4% of specimens, and HPV was positive in 14.5%. Eighty-four CIN-3-positive specimens were detected, including 55 that tested ASCUS-positive/HPV-positive, 11 that tested negative for intraepithelial lesion or malignancy (NILM)/HPV-positive, 10 that tested ASCUS-positive/HPV-negative, 3 that tested NILM/HPV-negative, and 5 tests that were unsatisfactory. There was no significant difference between NILM/HPV-positive and ASCUS-positive/HPV-negative CIN-3 in terms of size, time to occurrence, the presence of a cytopathic effect, screening history, race, or age. Six of 11 NILM/HPV-positive cases were reclassified as ASCUS, indicating an interpreting error of 55% and a sampling error of 45%. No ASCUS-positive/HPV-negative cases were reclassified. Seven cases of CIN-3 with positive cytology were HPV-negative. There are no significant clinical or pathologic differences between NILM/HPV-positive and ASCUS-positive/HPV-negative CIN-3-positive specimens. Cytologic sampling or interpretation remains the main reason for discrepancies. However, HPV-negative CIN-3 with positive cytology exists and may be missed by primary HPV screening. Cancer Cytopathol 2017;125:795-805. © 2017 American Cancer Society. © 2017 American Cancer Society.

Microfabricated linear Paul-Straubel ion trap

DOEpatents

Mangan, Michael A [Albuquerque, NM; Blain, Matthew G [Albuquerque, NM; Tigges, Chris P [Albuquerque, NM; Linker, Kevin L [Albuquerque, NM

2011-04-19

An array of microfabricated linear Paul-Straubel ion traps can be used for mass spectrometric applications. Each ion trap comprises two parallel inner RF electrodes and two parallel outer DC control electrodes symmetric about a central trap axis and suspended over an opening in a substrate. Neighboring ion traps in the array can share a common outer DC control electrode. The ions confined transversely by an RF quadrupole electric field potential well on the ion trap axis. The array can trap a wide array of ions.

Sequential acquisition of human papillomavirus (HPV) infection of the anus and cervix: the Hawaii HPV Cohort Study.

PubMed

Goodman, Marc T; Shvetsov, Yurii B; McDuffie, Katharine; Wilkens, Lynne R; Zhu, Xuemei; Thompson, Pamela J; Ning, Lily; Killeen, Jeffrey; Kamemoto, Lori; Hernandez, Brenda Y

2010-05-01

Relatively little is known about the epidemiology of anal human papillomavirus (HPV) infection in healthy women and its association with cervical HPV infection. he association of an incident cervical (or anal) HPV infection with the subsequent risk of a genotype-concordant incident anal (or cervical) HPV infection was examined in a longitudinal cohort study of 751 sexually active women. Age-adjusted hazard ratios, obtained using Cox regression, served as measurements of relative risk (RR). Among women, the RR of acquiring an anal HPV infection after a cervical infection with HPV of the same genotype was 20.5 (95% confidence interval, 16.3-25.7), and the RR of acquiring a cervical HPV infection after an anal infection with HPV of the same genotype was 8.8 (95% confidence interval, 6.4-12.2), compared with women without a previous anal/cervical infection with HPV of a concordant genotype. RRs varied by phylogenetic species, with HPV alpha3/alpha15 and alpha1/alpha8/alpha10 types having a greater likelihood than other types of HPV infecting the anus among women with a previous infection at the cervix with HPV of the same genotype. It appears common for anal and cervical HPV infections to occur consecutively. The high degree of genotype-specific concordance suggests that the cervix (vagina) and anus may serve as reservoirs for HPV infection at the other anatomical site.

Human papillomavirus and vaccine-related perceptions among men who have sex with men: a systematic review.

PubMed

Nadarzynski, Tom; Smith, Helen; Richardson, Daniel; Jones, Christina J; Llewellyn, Carrie D

2014-11-01

Targeted human papillomavirus (HPV) vaccine could prevent HPV-related cancers and genital warts among men who have sex with men (MSM). In order to develop effective vaccination programmes for MSM, it is crucial to understand their knowledge, beliefs about HPV and attitudes towards HPV vaccine. A systematic search of 10 databases examined articles investigating HPV knowledge and HPV-related perceptions among MSM. Each paper was assessed to identify potential research directions in the context of targeted HPV vaccination for MSM. We identified 16 studies that included 5185 MSM and conducted mainly in North America. Generally, participants were over 26 years old, had poor-to-moderate knowledge about HPV and were not concerned about HPV-related diseases. Over a half of MSM were willing to accept HPV vaccine, if offered. However, there was large variability in HPV vaccine acceptability, partially due to inconsistencies in methods of ascertainment but also different levels of HPV vaccine awareness. Despite several misconceptions and poor knowledge of HPV infection, MSM might be receptive to HPV vaccination. However, further research is needed to identify which factors contribute to potential vaccine uptake in hypothetical MSM-targeted HPV vaccination. Future studies need to target those MSM with little sexual experience, who would benefit most from HPV vaccination. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

HPV prevalence in a Mid-European oral squamous cell cancer population: a cohort study.

PubMed

Dalla Torre, Daniel; Burtscher, Doris; Soelder, Elisabeth; Offermanns, Vincent; Rasse, Michael; Puelacher, Wolfgang

2018-04-29

HPV infection has been investigated intensively regarding oropharyngeal carcinoma. However, there is still lack of knowledge about the impact of oral HPV infections concerning oral squamous cell carcinoma. The present study investigates the prevalence of oral HPV infection in such patients, identifying possible differences between HPV+ and HPV- patients. 106 consequent patients were investigated. After completion of a study questionnaire regarding risk factors, a brush smear sample was taken in each subject to identify the individual oral HPV status (overall/low risk/high risk). 35.8% of the patients were tested positive for HPV in the oral cavity (14% low risk, 28.3% high risk). Patients with oral HPV infection and high risk HPV infection were significantly younger (p<0.001) and had a higher alcohol consumption (p=0.0075 resp. p=0.0022). A high number of different sexual partners was significantly correlated with any type of HPV infection. Finally, patients with high risk oral HPV infection had experienced more tooth extractions during their lifetime. Oral HPV infections may influence the course of disease of oral squamous cell carcinoma as HPV+ patients are about 10 years younger. It seems that high alcohol consumption facilitates high risk HPV infection. It may be presumed that both alcohol consumption and high risk oral HPV infection act synergistically, explaining earlier cancer onset. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Jet Noise Source Localization Using Linear Phased Array

NASA Technical Reports Server (NTRS)

Agboola, Ferni A.; Bridges, James

2004-01-01

A study was conducted to further clarify the interpretation and application of linear phased array microphone results, for localizing aeroacoustics sources in aircraft exhaust jet. Two model engine nozzles were tested at varying power cycles with the array setup parallel to the jet axis. The array position was varied as well to determine best location for the array. The results showed that it is possible to resolve jet noise sources with bypass and other components separation. The results also showed that a focused near field image provides more realistic noise source localization at low to mid frequencies.

Human Papillomavirus (HPV) virion induced cancer and subfertility, two sides of the same coin.

PubMed

Depuydt, C E; Beert, J; Bosmans, E; Salembier, G

2016-12-01

In the natural history of HPV infections, the HPV virions can induce two different pathways, namely the infec- tious virion producing pathway and the clonal transforming pathway. An overview is given of the burden that is associated with HPV infections that can both lead to cervical cancer and/or temporal subfertility. That HPV infections cause serious global health burden due to HPV-associated cancers is common knowledge, but that it is also responsible for a substantial part of idiopathic subfertility is greatly underestimated. The bulk of the detected HPV DNA whether in men or women is however infectious from origin. Because the dissociation between HPV viruses and HPV virions or infection and disease remains difficult for clinicians as well as for HPV detection, we propose a review of the different effects caused by the two different HPV virion induced pathways, and highlight the mechanisms that are responsible for causing transient subfertility and cancer.

Role of human papillomavirus in oral squamous cell carcinoma and oral potentially malignant disorders: A review of the literature

PubMed Central

Gupta, Shikha; Gupta, Sunita

2015-01-01

Human papillomaviruses (HPVs) are epitheliotropic viruses with an affinity for keratinocytes and are principally found in the anogenital tract, urethra, skin, larynx, tracheobronchial and oral mucosa. On the basis of high, but variable frequency of HPV in oral squamous cell carcinoma (OSCC), malignant potential of HPV infection has been hypothesized but not definitely confirmed. The aim of this review was to highlight the genomic structure and possible mechanism of infection and carcinogenesis by HPV in the oral mucosa and to review the frequency of HPV prevalence in OSCC and oral potentially malignant disorders. A computer database search was performed through the use of PubMed from 1994 to 2014. Search keywords used were: HPV and oral cancer, HPV and oral leukoplakia, HPV and oral lichen planus, HPV and OSCC, HPV and verrucous carcinoma, HPV and proliferative verrucous leukoplakia, HPV and oral papilloma. PMID:26097339

Role of the DNA Damage Response in Human Papillomavirus RNA Splicing and Polyadenylation.

PubMed

Nilsson, Kersti; Wu, Chengjun; Schwartz, Stefan

2018-06-12

Human papillomaviruses (HPVs) have evolved to use the DNA repair machinery to replicate its DNA genome in differentiated cells. HPV activates the DNA damage response (DDR) in infected cells. Cellular DDR factors are recruited to the HPV DNA genome and position the cellular DNA polymerase on the HPV DNA and progeny genomes are synthesized. Following HPV DNA replication, HPV late gene expression is activated. Recent research has shown that the DDR factors also interact with RNA binding proteins and affects RNA processing. DDR factors activated by DNA damage and that associate with HPV DNA can recruit splicing factors and RNA binding proteins to the HPV DNA and induce HPV late gene expression. This induction is the result of altered alternative polyadenylation and splicing of HPV messenger RNA (mRNA). HPV uses the DDR machinery to replicate its DNA genome and to activate HPV late gene expression at the level of RNA processing.

Iterative color-multiplexed, electro-optical processor.

PubMed

Psaltis, D; Casasent, D; Carlotto, M

1979-11-01

A noncoherent optical vector-matrix multiplier using a linear LED source array and a linear P-I-N photodiode detector array has been combined with a 1-D adder in a feedback loop. The resultant iterative optical processor and its use in solving simultaneous linear equations are described. Operation on complex data is provided by a novel color-multiplexing system.

Multiband selection with linear array detectors

NASA Technical Reports Server (NTRS)

Richard, H. L.; Barnes, W. L.

1985-01-01

Several techniques that can be used in an earth-imaging system to separate the linear image formed after the collecting optics into the desired spectral band are examined. The advantages and disadvantages of the Multispectral Linear Array (MLA) multiple optics, the MLA adjacent arrays, the imaging spectrometer, and the MLA beam splitter are discussed. The beam-splitter design approach utilizes, in addition to relatively broad spectral region separation, a movable Multiband Selection Device (MSD), placed between the exit ports of the beam splitter and a linear array detector, permitting many bands to be selected. The successful development and test of the MSD is described. The device demonstrated the capacity to provide a wide field of view, visible-to-near IR/short-wave IR and thermal IR capability, and a multiplicity of spectral bands and polarization measuring means, as well as a reasonable size and weight at minimal cost and risk compared to a spectrometer design approach.

Fiber bundle phase conjugate mirror

DOEpatents

Ward, Benjamin G.

2012-05-01

An improved method and apparatus for passively conjugating the phases of a distorted wavefronts resulting from optical phase mismatch between elements of a fiber laser array are disclosed. A method for passively conjugating a distorted wavefront comprises the steps of: multiplexing a plurality of probe fibers and a bundle pump fiber in a fiber bundle array; passing the multiplexed output from the fiber bundle array through a collimating lens and into one portion of a non-linear medium; passing the output from a pump collection fiber through a focusing lens and into another portion of the non-linear medium so that the output from the pump collection fiber mixes with the multiplexed output from the fiber bundle; adjusting one or more degrees of freedom of one or more of the fiber bundle array, the collimating lens, the focusing lens, the non-linear medium, or the pump collection fiber to produce a standing wave in the non-linear medium.

Natural course of distant metastases following radiotherapy or chemoradiotherapy in HPV-related oropharyngeal cancer.

PubMed

Huang, Shao Hui; Perez-Ordonez, Bayardo; Weinreb, Ilan; Hope, Andrew; Massey, Christine; Waldron, John N; Kim, John; Bayley, Andrew J; Cummings, Bernard; Cho, B C John; Ringash, Jolie; Dawson, Laura A; Siu, Lillian L; Chen, Eric; Irish, Jonathan; Gullane, Patrick; Hui, Angela; Liu, Fei-Fei; Shen, Xiaowei; Xu, Wei; O'Sullivan, Brian

2013-01-01

To describe the natural course of distant metastases (DMs) following radiotherapy (RT) or chemoradiotherapy (CRT) in HPV(+) oropharyngeal carcinoma (OPC). OPC treated with RT/CRT from 1/1/2000 to 5/31/2010 were reviewed. The natural course of DM were compared between HPV(+) and HPV(-) cohorts. Median follow-up was 3.9 years. The DM rate were similar (11% vs. 15% at 3-years, p=0.25) between the HPV(+) (n=457) vs. the HPV(-) (n=167) cases. While almost all (24/25) HPV(-) DM occurred within 2-years following RT (1 was at 2.1 years), 7/54 (13%) of HPV(+) DM were detected beyond 3 years (up to 5.3 years). Disseminating to >2 organs occurred in 18 (33%) HPV(+) vs. none in HPV(-). Post-DM survival rates were 11% vs. 4% at 2-years (p=0.02) for the HPV(+) vs. HPV(-) cases respectively. 5/6 HPV(+) with lung oligo-metastasis were still alive with stable disease beyond 2-years after salvage procedures for DM (chemotherapy: 3; surgical resection: 2; radiotherapy: 1). Although DM rates are similar, the natural course of HPV(+) DM differs from that of HPV(-) patients: it may occur after a longer interval, often with a "disseminating" phenotype, and a small number may have prolonged survival after salvage for DM. Copyright © 2012 Elsevier Ltd. All rights reserved.

High rates of incident and prevalent anal human papillomavirus infection among young men who have sex with men.

PubMed

Glick, Sara Nelson; Feng, Qinghua; Popov, Viorica; Koutsky, Laura A; Golden, Matthew R

2014-02-01

There are few published estimates of anal human papillomavirus (HPV) infection rates among young men who have sex with men (YMSM). We estimated incidence and prevalence of type-specific anal HPV infection using clinician-collected anal swabs for HPV DNA testing obtained during a 1-year prospective study of 94 YMSM (mean age, 21 years) in Seattle. Seventy percent of YMSM had any HPV infection detected during the study, and HPV-16 and/or -18 were detected in 37%. The incidence rate for any new HPV infection was 38.5 per 1000 person-months and 15.3 per 1000 person-months for HPV-16/18; 19% had persistent HPV-16/18 infection. No participant tested positive for all 4 HPV types in the quadrivalent vaccine. The number of lifetime male receptive anal sex partners was significantly associated with HPV infection. The prevalence of HPV-16/18 was 6% among YMSM with a history of 1 receptive anal sex partner and 31% among YMSM with ≥ 2 partners. Although the high prevalence of HPV among YMSM highlights the desirability of vaccinating all boys as a strategy to avert the morbidity of HPV infection, most YMSM appear to remain naive to either HPV-16 or -18 well into their sexual lives and would benefit from HPV immunization.

A Novel Strategy for Human Papillomavirus Detection and Genotyping with SybrGreen and Molecular Beacon Polymerase Chain Reaction

PubMed Central

Szuhai, Károly; Sandhaus, Emily; Kolkman-Uljee, Sandra M.; Lemaître, Marc; Truffert, Jean-Christophe; Dirks, Roeland W.; Tanke, Hans J.; Fleuren, Gert Jan; Schuuring, Ed; Raap, Anton K.

2001-01-01

Human papillomaviruses (HPVs) play an important role in the pathogenesis of cervical cancer. For identification of the large number of different HPV types found in (pre)malignant lesions, a robust methodology is needed that combines general HPV detection with HPV genotyping. We have developed for formaldehyde-fixed samples a strategy that, in a homogenous, real-time fluorescence polymerase chain reaction (PCR)-based assay, accomplishes general HPV detection by SybrGreen reporting of HPV-DNA amplicons, and genotyping of seven prevalent HPV types (HPV-6, -11, -16, -18, -31, -33, -45) by real-time molecular beacon PCR. The false-positive rate of the HPV SybrGreen-PCR was 4%, making it well suited as a prescreening, general HPV detection technology. The type specificity of the seven selected HPV molecular beacons was 100% and double infections were readily identified. The multiplexing capacity of the HPV molecular beacon PCR was analyzed and up to three differently labeled molecular beacons could be used in one PCR reaction without observing cross talk. The inherent quantitation capacities of real-time fluorescence PCR allowed the determination of average HPV copy number per cell. We conclude that the HPV SybrGreen-PCR in combination with the HPV molecular beacon PCR provides a robust, sensitive, and quantitative general HPV detection and genotyping methodology. PMID:11696426

Human Papillomavirus Community in Healthy Persons, Defined by Metagenomics Analysis of Human Microbiome Project Shotgun Sequencing Data Sets

PubMed Central

Ma, Yingfei; Madupu, Ramana; Karaoz, Ulas; Nossa, Carlos W.; Yang, Liying; Yooseph, Shibu; Yachimski, Patrick S.; Brodie, Eoin L.; Nelson, Karen E.

2014-01-01

ABSTRACT Human papillomavirus (HPV) causes a number of neoplastic diseases in humans. Here, we show a complex normal HPV community in a cohort of 103 healthy human subjects, by metagenomics analysis of the shotgun sequencing data generated from the NIH Human Microbiome Project. The overall HPV prevalence was 68.9% and was highest in the skin (61.3%), followed by the vagina (41.5%), mouth (30%), and gut (17.3%). Of the 109 HPV types as well as additional unclassified types detected, most were undetectable by the widely used commercial kits targeting the vaginal/cervical HPV types. These HPVs likely represent true HPV infections rather than transitory exposure because of strong organ tropism and persistence of the same HPV types in repeat samples. Coexistence of multiple HPV types was found in 48.1% of the HPV-positive samples. Networking between HPV types, cooccurrence or exclusion, was detected in vaginal and skin samples. Large contigs assembled from short HPV reads were obtained from several samples, confirming their genuine HPV origin. This first large-scale survey of HPV using a shotgun sequencing approach yielded a comprehensive map of HPV infections among different body sites of healthy human subjects. IMPORTANCE This nonbiased survey indicates that the HPV community in healthy humans is much more complex than previously defined by widely used kits that are target selective for only a few high- and low-risk HPV types for cervical cancer. The importance of nononcogenic viruses in a mixed HPV infection could be for stimulating or inhibiting a coexisting oncogenic virus via viral interference or immune cross-reaction. Knowledge gained from this study will be helpful to guide the designing of epidemiological and clinical studies in the future to determine the impact of nononcogenic HPV types on the outcome of HPV infections. PMID:24522917

Anal Human Papillomavirus Infection among HIV-Infected Men in Korea

PubMed Central

Lee, Chang Hun; Lee, Sun Hee; Lee, Shinwon; Cho, Heerim; Kim, Kye-Hyung; Lee, Jung Eun; Jung, Eun ju; Lee, Su jin; Kim, Eun Jung; Kim, Ki Hyung; Moon, Eunsoo; Cho, Hong Je

2016-01-01

Background Little is known about the epidemiology on human papillomavirus (HPV) infection among HIV-infected men in Korea. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among HIV-infected men in Korea. Methods A single-center cross-sectional study was conducted with HIV-infected men in Korea. Participants completed a detailed sexual behavior risk factor questionnaire. Anal samples were collected for cytology and HPV genotyping. Factors associated with anal HPV infection were assessed using multivariable logistic regression, stratifying by sexual behaviour. Results A total of 201 HIV-infected men were included in the study: 133 were from men who have sex with men (MSM) and 68 from men who have sex with women (MSW). Any anal HPV infection was detected in 82.7% of HIV-infected MSM and in 51.5% of HIV- infected MSW (P < 0.001). High-risk HPV (HR-HPV) prevalence was higher among MSM (47.4%) than MSW (25.0%; P = 0.002). The HR-HPV types identified most frequently were HPV 16 (11%), HPV 18 (9.9%), and HPV 58 (5%) in MSM, and HPV 58(11%) and HPV 16 (8.9%) in MSW. Prevalence of any HPV types in 9-valent vaccine types was higher among MSM than MSW (47.4% vs 22.1%. P = 0.001). Abnormal anal cytology was more commonly detected in MSM than MSW (42.9% vs.19.1%, P < 0.001). In HIV-infected MSM, higher number of lifetime male sex partners was significantly associated with any anal HPV infection, but age was a significant risk factor associated with anal HR-HPV infection. Conclusion Anal HPV infection was highly prevalent in HIV-infected MSM in Korea, and also commonly found in HIV-infected MSW. In HIV-infected MSM, the significant risk factor for being infected with any HPV infection was lifetime number of male sexual partners, and with anal oncogenic HPV infection was age. PMID:27548632

Anal Human Papillomavirus Infection among HIV-Infected Men in Korea.

PubMed

Lee, Chang Hun; Lee, Sun Hee; Lee, Shinwon; Cho, Heerim; Kim, Kye-Hyung; Lee, Jung Eun; Jung, Eun Ju; Lee, Su Jin; Kim, Eun Jung; Kim, Ki Hyung; Moon, Eunsoo; Cho, Hong Je

2016-01-01

Little is known about the epidemiology on human papillomavirus (HPV) infection among HIV-infected men in Korea. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among HIV-infected men in Korea. A single-center cross-sectional study was conducted with HIV-infected men in Korea. Participants completed a detailed sexual behavior risk factor questionnaire. Anal samples were collected for cytology and HPV genotyping. Factors associated with anal HPV infection were assessed using multivariable logistic regression, stratifying by sexual behaviour. A total of 201 HIV-infected men were included in the study: 133 were from men who have sex with men (MSM) and 68 from men who have sex with women (MSW). Any anal HPV infection was detected in 82.7% of HIV-infected MSM and in 51.5% of HIV- infected MSW (P < 0.001). High-risk HPV (HR-HPV) prevalence was higher among MSM (47.4%) than MSW (25.0%; P = 0.002). The HR-HPV types identified most frequently were HPV 16 (11%), HPV 18 (9.9%), and HPV 58 (5%) in MSM, and HPV 58(11%) and HPV 16 (8.9%) in MSW. Prevalence of any HPV types in 9-valent vaccine types was higher among MSM than MSW (47.4% vs 22.1%. P = 0.001). Abnormal anal cytology was more commonly detected in MSM than MSW (42.9% vs.19.1%, P < 0.001). In HIV-infected MSM, higher number of lifetime male sex partners was significantly associated with any anal HPV infection, but age was a significant risk factor associated with anal HR-HPV infection. Anal HPV infection was highly prevalent in HIV-infected MSM in Korea, and also commonly found in HIV-infected MSW. In HIV-infected MSM, the significant risk factor for being infected with any HPV infection was lifetime number of male sexual partners, and with anal oncogenic HPV infection was age.

National HPV immunisation programme: knowledge and acceptance of mothers attending an obstetrics clinic at a teaching hospital, Kuala Lumpur.

PubMed

Ezat, Sharifa Wan Puteh; Hod, Rozita; Mustafa, Jamsiah; Mohd Dali, Ahmad Zailani Hatta; Sulaiman, Aqmar Suraya; Azman, Azlin

2013-01-01

Introduction of the HPV vaccine is a forefront primary prevention method in reducing the incidence of carcinogenic human papillomavirus (HPV) and cervical cancer. The Malaysia government has implemented the National HPV immunisation programme since 2010, supplying HPV vaccine free to targeted 13 year olds. This study aimed to explore the level of knowledge among mothers on cervical cancer, HPV, HPV vaccine and National HPV (NHPV) immunisation programme since its' implementation. It also assessed acceptance of mothers towards HPV vaccine being administered to their daughter, son or themselves. A cross sectional study was conducted on 155 respondents using self-administered questionnaires; conducted in December 2012 at the Obstetrics and Gynaecology Clinic in a teaching hospital in Kuala Lumpur. Respondents were selected using a multistage sampling technique. A response rate of 100% was obtained. Overall, 51.0% of mothers had good knowledge, with 55% having good knowledge of cervical cancer, 54.2% for both HPV and the National HPV immunisation programme and 51.0% for the HPV vaccine. Regression analyses showed that ethnicity was associated with knowledge on cervical cancer (p=0.003) while education was associated with knowledge on HPV (p=0.049). Three factors are associated with knowledge of the National HPV immunisation programme; ethnicity (p=0.017), mothers' education (p=0.0005) and number of children (p=0.020). The acceptance of HPV vaccine to be administered among daughter was the highest at 87.1%, followed by for mothers themselves at 73.5%, and the least is for sons 62.6%. This study found that the overall level of knowledge was moderate. Adequate information on cervical cancer, HPV, HPV vaccination and the National HPV immunisation programme should be provided to mothers in order to increase acceptance of the HPV vaccine which can reduce the disease burden in the future.

Identification and characterization of HPV-independent cervical cancers.

PubMed

Banister, Carolyn E; Liu, Changlong; Pirisi, Lucia; Creek, Kim E; Buckhaults, Phillip J

2017-02-21

Human papillomavirus (HPV) initiates cervical cancer, and continuous expression of HPV oncogenes E6 and E7 is thought to be necessary to maintain malignant growth. Current therapies target proliferating cells, rather than specific pathways, and most experimental therapies specifically target E6/E7. We investigated the presence and expression of HPV in cervical cancer, to correlate HPV oncogene expression with clinical and molecular features of these tumors that may be relevant to new targeted therapies. While virtually all cervical cancers contained HPV DNA, and most expressed E6/E7 (HPV-active), a subset (8%) of HPV DNA-positive cervical cancers did not express HPV transcripts (HPV-inactive). HPV-inactive tumors occurred in older women (median 54 vs. 45 years, p = 0.02) and were associated with poorer survival (median 715 vs 3046 days, p = 0.0003). Gene expression profiles of HPV-active and -inactive tumors were distinct. HPV-active tumors expressed E2F target genes and increased AKT/MTOR signaling. HPV-inactive tumors had increased WNT/β-catenin and Sonic Hedgehog signaling. Substantial genome-wide differences in DNA methylation were observed. HPV-inactive tumors had a global decrease in DNA methylation; however, many promoter-associated CpGs were hypermethylated. Many inflammatory response genes showed promoter methylation and decreased expression. The somatic mutation landscapes were significantly different. HPV-active tumors carried few somatic mutations in driver genes, whereas HPV-inactive tumors were enriched for non-synonymous somatic mutations (p-value < 0.0000001) specifically targeting TP53, ARID, WNT, and PI3K pathways. The Cancer Genome Atlas (TCGA) cervical cancer data were analyzed. Many of the gene expression changes and somatic mutations found in HPV-inactive tumors alter pathways for which targeted therapeutics are available. Treatment strategies focused on WNT, PI3K, or TP53 mutations may be effective against HPV-inactive tumors and could improve survival for these cervical cancer patients.

Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women.

PubMed

Ruiz-Sternberg, Ángela María; Moreira, Edson D; Restrepo, Jaime A; Lazcano-Ponce, Eduardo; Cabello, Robinson; Silva, Arnaldo; Andrade, Rosires; Revollo, Francisco; Uscanga, Santos; Victoria, Alejandro; Guevara, Ana María; Luna, Joaquín; Plata, Manuel; Dominguez, Claudia Nossa; Fedrizzi, Edison; Suarez, Eugenio; Reina, Julio C; Ellison, Misoo C; Moeller, Erin; Ritter, Michael; Shields, Christine; Cashat, Miguel; Perez, Gonzalo; Luxembourg, Alain

2018-06-01

A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV) vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV) vaccine. Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16-26 years, and an immunogenicity and safety study in girls and boys aged 9-15 years. Participants (N=5312) received vaccination at Day 1, Month 2, and Month 6. Gynecological swabs were collected regularly in young women for cytological and HPV DNA testing. Serum was analyzed for HPV antibodies in all participants. Adverse events (AEs) were also monitored in all participants. The 9vHPV vaccine prevented HPV 31-, 33-, 45-, 52-, and 58-related high-grade cervical, vulvar, and vaginal dysplasia with 92.3% efficacy (95% confidence interval 54.4, 99.6). Anti-HPV6, 11, 16, and 18 geometric mean titers at Month 7 were similar in the 9vHPV and qHPV vaccination groups. Anti-HPV antibody responses following vaccination were higher among girls and boys than in young women. Most (>99%) 9vHPV vaccine recipients seroconverted for all 9 HPV types at Month 7. Antibody responses to the 9 HPV types persisted over 5 years. The most common AEs were injection-site related, mostly of mild to moderate intensity. The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Latin American young women, girls, and boys. These data support 9vHPV vaccination programs in Latin America, a region with substantial cervical cancer burden. Copyright © 2018 Merck Sharp & Dohme Corp., and The Authors. Published by Elsevier B.V. All rights reserved.

Human papillomavirus in esophageal squamous cell carcinoma in Colombia and Chile

PubMed Central

Castillo, Andres; Aguayo, Francisco; Koriyama, Chihaya; Torres, Miyerlandi; Carrascal, Edwin; Corvalan, Alejandro; Roblero, Juan P; Naquira, Cecilia; Palma, Mariana; Backhouse, Claudia; Argandona, Jorge; Itoh, Tetsuhiko; Shuyama, Karem; Eizuru, Yoshito; Akiba, Suminori

2006-01-01

AIM: To examine the presence of human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC) specimens collected from Colombia and Chile located in the northern and southern ends of the continent, respectively. METHODS: We examined 47 and 26 formalin-fixed and paraffin-embedded ESCC specimens from Colombia and Chile, respectively. HPV was detected using GP5+/GP6+ primer pair for PCR, and confirmed by Southern blot analysis. Sequencing analysis of L1 region fragment was used to identify HPV genotype. In addition, P16INK4A protein immunostaining of all the specimens was conducted. RESULTS: HPV was detected in 21 ESCC specimens (29%). Sequencing analysis of L1 region fragment identified HPV-16 genome in 6 Colombian cases (13%) and in 5 Chilean cases (19%). HPV-18 was detected in 10 cases (21%) in Colombia but not in any Chilean case. Since Chilean ESCC cases had a higher prevalence of HPV-16 (without statistical significance), but a significantly lower prevalence of HPV-18 than in Colombian cases (P = 0.011) even though the two countries have similar ESCC incidence rates, the frequency of HPV-related ESCC may not be strongly affected by risk factors affecting the incidence of ESCC. HPV-16 genome was more frequently detected in p16 positive carcinomas, although the difference was not statistically significant. HPV-18 detection rate did not show any association with p16 expression. Well-differentiated tumors tended to have either HPV-16 or HPV-18 but the association was not statistically significant. HPV genotypes other than HPV-16 or 18 were not detected in either country. CONCLUSION: HPV-16 and HPV-18 genotypes can be found in ESCC specimens collected from two South American countries. Further studies on the relationship between HPV-16 presence and p16 expression in ESCC would aid understanding of the mechanism underlying the presence of HPV in ESCC. PMID:17036393

Performance of a Cartridge-Based Assay for Detection of Clinically Significant Human Papillomavirus (HPV) Infection: Lessons from VALGENT (Validation of HPV Genotyping Tests)

PubMed Central

Geraets, Daan; Cuzick, Jack; Cadman, Louise; Moore, Catherine; Vanden Broeck, Davy; Padalko, Elisaveta; Quint, Wim; Arbyn, Marc

2016-01-01

The Validation of Human Papillomavirus (HPV) Genotyping Tests (VALGENT) studies offer an opportunity to clinically validate HPV assays for use in primary screening for cervical cancer and also provide a framework for the comparison of analytical and type-specific performance. Through VALGENT, we assessed the performance of the cartridge-based Xpert HPV assay (Xpert HPV), which detects 14 high-risk (HR) types and resolves HPV16 and HPV18/45. Samples from women attending the United Kingdom cervical screening program enriched with cytologically abnormal samples were collated. All had been previously tested by a clinically validated standard comparator test (SCT), the GP5+/6+ enzyme immunoassay (EIA). The clinical sensitivity and specificity of the Xpert HPV for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) and CIN3+ relative to those of the SCT were assessed as were the inter- and intralaboratory reproducibilities according to international criteria for test validation. Type concordance for HPV16 and HPV18/45 between the Xpert HPV and the SCT was also analyzed. The Xpert HPV detected 94% of CIN2+ and 98% of CIN3+ lesions among all screened women and 90% of CIN2+ and 96% of CIN3+ lesions in women 30 years and older. The specificity for CIN1 or less (≤CIN1) was 83% (95% confidence interval [CI], 80 to 85%) in all women and 88% (95% CI, 86 to 91%) in women 30 years and older. Inter- and intralaboratory agreements for the Xpert HPV were 98% and 97%, respectively. The kappa agreements for HPV16 and HPV18/45 between the clinically validated reference test (GP5+/6+ LMNX) and the Xpert HPV were 0.92 and 0.91, respectively. The clinical performance and reproducibility of the Xpert HPV are comparable to those of well-established HPV assays and fulfill the criteria for use in primary cervical cancer screening. PMID:27385707

Human papillomavirus type specific risk of progression and remission during long-term follow-up of equivocal and low-grade HPV-positive cervical smears.

PubMed

Vintermyr, Olav Karsten; Andersland, Marie Songstad; Bjørge, Tone; Skar, Robert; Iversen, Ole Erik; Nygård, Mari; Haugland, Hans Kristian

2018-03-23

The prevalence of clinically relevant HPV types and their specific risk for progression and regression in women with atypical squamous cells of uncertain significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) were studied in a routine screening population. A 4-year cohort of women (n = 820) with ASCUS/LSIL and a positive HPV test in triage were followed for 6-9 years. The progression risks for CIN2+/CIN3+ were determined for single (71.2%) and multiple HPV infections (28.8%). The CIN2+ progression risk for all HPV 16, all HPV 35, single HPV 16 and single HPV 35 infections were 65.3% (95% CI: 59.6-71.0), 64.4% (95% CI: 50.4-78.4), 63.8% (95% CI: 56.2-71.4) and 73.7% (95% CI: 53.9-93.5), respectively. Based on CIN2+ progression risks four main groups were defined; the HPV 16 group, the HPV 31/33/35 group, the HPV 18/45/51/52 group and the HPV 39/56/58/59/66/68 group with progression risks of 65.3% (95% CI: 59.6-71.0), 62.1% (95% CI: 54.8-69.4), 52.6 (95% CI: 45.9-59.3) and 39.5 (95% CI: 33.0-46.0), respectively. In multivariate analyses, women in the age group 40-49 years had an increased risk of CIN2+ progression. As for CIN3+, HPV 16 had a higher progression risk than other HPV risk groups (p < 0.05). In multiple infections only HPV 16 had a significant additive CIN3+ progression risk (p < 0.05) as compared to other HPV risk groups. In summary, HPV types 16 and 35, including the HPV risk group 31/33/35, had a similar CIN2+ progression risk, but only HPV 16 had a higher risk for CIN3+ progression. © 2018 UICC.

Detection of human papillomavirus (HPV) DNA in human prostatic tissues by polymerase chain reaction (PCR).

PubMed

Sarkar, F H; Sakr, W A; Li, Y W; Sreepathi, P; Crissman, J D

1993-01-01

Human papillomavirus (HPV) infections are strongly linked to the pathogenesis of uterine cervical neoplasms, and have been implicated in other cancers of the female genital tract. In contrast, the association of HPV with the cancers of the male urogenital tract is less evident, except in anal and penile cancers. However, recent studies reporting the prevalence of HPV infections in human prostate cancers (60-100% HPV 16 positive vs. no infection of HPV) have raised controversies regarding the prevalence of HPV in benign and neoplastic human prostate. We investigated the prevalence of HPV infections in prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinomas in 23 surgically resected prostates. Polymerase chain reaction (PCR) was used to amplify HPV 6b/11, 16, and 18 specific DNA sequences, using type specific HPV primers selected from the transforming gene E6-E7. The areas of PIN and cancer in 6 microns H&E stained tissue sections were identified, and respective areas of PIN and cancer were isolated from the adjacent serial sections and used for DNA amplification and HPV detection (Fig. 1). Our results demonstrated the presence of HPV 16 in three carcinomas (13%), using type specific primers in PCR amplified samples. We were not able to demonstrate the presence of other HPV types (HPV 6b/11 or HPV 18) in any of the samples using specific primers. Two of these prostates showed relatively strong positive signals by dot blot analysis, when hybridized with a 32P-labeled HPV 16 type specific oligonucleotide probe. One more sample showed weak positivity, when hybridized with a 32P-labeled HPV 16 type specific oligonucleotide probe. Subsequently, we have confirmed these results by Southern hybridization of the samples transferred to nylon membrane after agarose gel electrophoresis and detected by HPV 16 type specific oligonucleotide probe, using chemiluminescent assay. We, therefore, conclude that HPV infections of the prostate in general are not as common as has been previously claimed by other investigators.

Maternal support for human papillomavirus vaccination in Honduras.

PubMed

Perkins, Rebecca B; Langrish, Sarah M; Cotton, Deborah J; Simon, Carol J

2011-01-01

Cervical cancer is a leading cause of cancer death for women in Latin America, and vaccinating against human papillomavirus (HPV) has the potential to limit this disease. We sought to determine Honduran women's awareness of HPV vaccination and interest in vaccinating their daughters against HPV. We interviewed mothers aged ≥17 at primary care clinics in Honduras. First, we collected demographic information and assessed knowledge related to cervical cancer prevention and awareness of HPV and HPV vaccination. Because most participants were not familiar with HPV, education about the relationships among HPV, sexual activity, and cervical cancer was provided before we asked participants if they would accept HPV vaccination for a 9-year-old daughter. We used multivariable logistic regression to determine predictors of vaccine acceptance. We interviewed 632 mothers. Only 13% had heard of HPV vaccination before the interview. After education, 91% would accept HPV vaccination for a 9-year-old daughter. Mothers who intended to vaccinate knew more at baseline about cervical cancer prevention than did those who did not endorse vaccination. Demographic characteristics did not predict vaccine acceptance. Few Honduran mothers were aware of HPV or HPV vaccination. However, most Honduran mothers would accept HPV vaccination for their daughters after receiving education about the relationship between HPV infection and cervical cancer. Baseline cervical cancer knowledge was associated with vaccine acceptance.

Prevalence of human papillomavirus in Indonesia: a population-based study in three regions

PubMed Central

Vet, J N I; de Boer, M A; van den Akker, B E W M; Siregar, B; Lisnawati; Budiningsih, S; Tyasmorowati, D; Moestikaningsih; Cornain, S; Peters, A A W; Fleuren, G J

2008-01-01

Cervical cancer is the most common cancer among women in the Indonesian population, yet little is known about the prevalence of human papillomavirus (HPV). We investigated age-specific prevalence of HPV types and possible risk factors of HPV positivity in a population-based sample of 2686 women, aged 15–70 years, in Jakarta, Tasikmalaya, and Bali, Indonesia. The overall HPV prevalence was 11.4%, age-standardized to the world standard population 11.6%. The most prevalent types found were HPV 52, HPV 16, HPV 18, and HPV 39, respectively, 23.2, 18.0, 16.1, and 11.8% of the high-risk HPV types. In 20.7% of infections, multiple types were involved. Different age-specific prevalence patterns were seen: overall high in Jakarta, and in Tasikmalaya, and declining with age in Bali. The number of marriages was most associated with HPV positivity (OR 1.81 95% CI 1.31–2.51)). Remarkably, in Indonesia HPV 16 and HPV 18 are equally common in the general population, as they are in cervical cancer. HPV 52 was the most prevalent type in the general population, suggesting that this type should be included when prophylactic HPV vaccination is introduced in Indonesia. PMID:18609756

Human Papillomavirus (HPV) Genotypes in Condylomas, Intraepithelial Neoplasia, and Invasive Carcinoma of the Penis Using Laser Capture Microdissection (LCM)-PCR: A Study of 191 Lesions in 43 Patients.

PubMed

Fernández-Nestosa, María J; Guimerà, Nuria; Sanchez, Diego F; Cañete-Portillo, Sofía; Velazquez, Elsa F; Jenkins, David; Quint, Wim; Cubilla, Antonio L

2017-06-01

Laser capture microdissection-polymerase chain reaction (LCM-PCR) supported by p16 was used for the first time to demonstrate human papillomavirus (HPV) DNA in histologically specific penile lesions, which were as follows: squamous hyperplasia (12 lesions, 10 patients), flat lesions (12 lesions, 5 patients), condylomas (26 lesions, 7 patients), penile intraepithelial neoplasia (PeIN) (115 lesions, 43 patients), and invasive squamous cell carcinomas (26 lesions, 26 patients). HPV was detected by whole-tissue section and LCM-PCR. LCM proved to be more precise than whole-tissue section in assigning individual genotypes to specific lesions. HPV was negative or very infrequent in squamous hyperplasia, differentiated PeIN, and low-grade keratinizing variants of carcinomas. HPV was strongly associated with condylomas, warty/basaloid PeIN, adjacent flat lesions, and warty/basaloid carcinomas. A single HPV genotype was found in each lesion. Some condylomas and flat lesions, especially those with atypia, were preferentially associated with high-risk HPV. Unlike invasive carcinoma, in which few genotypes of HPV were involved, there were 18 HPV genotypes in PeIN, usually HPV 16 in basaloid PeIN but marked HPV heterogeneity in warty PeIN (11 different genotypes). Variable and multiple HPV genotypes were found in multicentric PeIN, whereas unicentric PeIN was usually related to a single genotype. There was a correspondence among HPV genotypes in invasive and associated PeIN. p16 was positive in the majority of HPV-positive lesions except condylomas containing LR-HPV. p16 was usually negative in squamous hyperplasia, differentiated PeIN, and low-grade keratinizing variants of squamous cell carcinomas. In summary, we demonstrated that LCM-PCR was a superior research technique for investigating HPV genotypes in intraepithelial lesions. A significant finding was the heterogeneity of HPV genotypes in PeIN and the differential association of HPV genotypes with subtypes of PeIN. The presence of atypia and high-risk HPV in condylomas and adjacent flat lesions suggests a precursor role, and the correspondence of HPV genotypes in invasive carcinomas and associated PeIN indicates a causal relation. Data presented support the bimodal hypothesis of penile cancer carcinogenesis in HPV-driven and non-HPV-driven carcinomas and justify the current WHO pathologic classification of PeIN in special subtypes.

Type- and age-specific distribution of human papillomavirus in women attending cervical cancer screening in Finland

PubMed Central

Leinonen, M K; Anttila, A; Malila, N; Dillner, J; Forslund, O; Nieminen, P

2013-01-01

Background: Large-scale data on type-specific HPV prevalences and disease burden are needed to monitor the impact of HPV vaccination and to plan for HPV-based cervical screening. Methods: 33 043 women (aged 25–65) were screened for HPV by a Hybrid Capture 2 (HC2) in a population-based programme. HPV-positive women (n=2574) were triaged by cytology and HPV genotyped using PCR-Luminex. Type-specific prevalence of HPV infection and its correlation to findings in cytology triage and histology as well as Population Attributable Fractions for a referral to colposcopy and findings in histology were calculated. Results: Among HC2-positive women, 61.5% had normal, 23.1% had ASC-US and 15.5% had LSIL or more severe (LSIL+) results in cytology. Out of HC2-positive samples, 57% contained the 13 Group 1/2A HPV types, which were targeted by the HC2, 15% contained Group 2B types, 8.5% Group 3 types and 30% were found to be negative in HPV genotyping. The proportion of samples positive for HPV by the HC2, but negative in HPV genotyping increased with age and decreased with increasing cytological abnormality. The most frequent types were HPV 16 (0.9% of screened women and 12.1% of the HC2-positive women), HPV 31 (0.7% and 8.9%, respectively) and HPV 52 (0.5% and 6.3%, respectively). The prevalence of Group 1/2A HPV types increased with increasing CIN grade and attributed 78.3% (95% CI 53.4–89.9) of the CIN 3+ lesions, while HPV 16 attributed 55.8% (40.0–67.5) of them. Conclusion: The type-specific prevalence of HPV were slightly lower than the average in international meta-analyses. Genotyping for HPV 16 better identified women with CIN 3+ than cytology triage at the threshold of LSIL+. The high proportion of women that were HC2-positive but HPV-negative in genotyping suggests that HPV genotyping may be useful also for validation of results in HPV screening. The large-scale HPV genotyping data were found to be directly useful for planning further preventive efforts for cervical cancer. PMID:24136148

Cervical cancer screening in a low-resource setting: a pilot study on an HPV-based screen-and-treat approach.

PubMed

Kunckler, Margot; Schumacher, Fanny; Kenfack, Bruno; Catarino, Rosa; Viviano, Manuela; Tincho, Eveline; Tebeu, Pierre-Marie; Temogne, Liliane; Vassilakos, Pierre; Petignat, Patrick

2017-07-01

Cervical cancer (CC) is the leading cause of cancer-related death among women in sub-Saharan Africa, primarily because of limited access to effective screening and preventive treatment. Our aim was to assess the feasibility of a human papillomavirus (HPV)-based CC screen-and-treat approach in a low-resource context. We recruited 1012 women aged 30-49 years through a CC screening campaign conducted in the District Hospital of Dschang, Cameroon. Participants performed HPV self-sampling, which was tested for high-risk HPV (HR-HPV) DNA using the point-of-care Xpert HPV assay. All HPV-positive women were invited for visual inspection with acetic acid and Lugol's iodine (VIA/VILI) to exclude CC or enable triage. A cervical sample for histological analysis was also collected. Women positive for HPV 16/18/45 and for other HR-HPV with pathological VIA/VILI were selected to undergo treatment with thermocoagulation. The HPV prevalence in the study population was 18.5% (n = 187); of these cases, 20 (10.6%), 42 (22.3%) and 140 (74.9%) were positive for HPV16, HPV18/45 and other HR-HPV types, respectively. Overall, 107/185 (57.8%) VIA/VILI examinations were classified as pathological and 78 (42.2%) as normal. Women positive for HPV16/18/45 were 4.2 times more likely to harbor cervical intraepithelial neoplasia grade 2 or worse (CIN2+) than those with other HPV types. The specificity of HPV 16/18/45 genotypes for detection of high-grade lesions among HR-HPV positive women was higher than that of VIA/VILI in all age groups. The sensitivity and specificity of VIA/VILI in detecting CIN2+ among HPV positive women were 80% and 44%, respectively. Overall, 110/121 screen-positive women (90.9%) were eligible for, and were treated with, thermocoagulation. An HPV-based screen-and-treat approach is feasible in a low-resource context and may contribute to improving the effectiveness of CC prevention programs. Immediate thermocoagulation treatment for women who are HPV16- and/or HPV18/45-positive is a practical approach for the treatment of CIN2+. The combination of HPV-testing and VIA/VILI for CC screening might reduce overtreatment. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

The effect of a booster dose of quadrivalent or bivalent HPV vaccine when administered to girls previously vaccinated with two doses of quadrivalent HPV vaccine.

PubMed

Gilca, Vladimir; Sauvageau, Chantal; Boulianne, Nicole; De Serres, Gatson; Crajden, Mel; Ouakki, Manale; Trevisan, Andrea; Dionne, Marc

2015-01-01

This randomized, blinded study evaluated the immunogenicity and safety of a booster dose of Gardasil (qHPV) or Cervarix (bHPV) when administered to 12-13 year-old girls who were vaccinated at the age of 9-10 with 2 doses of qHPV (0-6 months). 366 out of 416 eligible girls participated in this follow-up study. Antibody titers were measured just before and one month post-booster. A Luminex Total IgG assay was used for antibody assessment and results are presented in Liminex Units (LU). Three years post-primary vaccination, 99-100% of subjects had detectable antibodies to 4HPV genotypes included in the qHPV with GMTs varying from 50 to 322 LU depending on genotype. After a booster dose of qHPV, a ≥4 fold increase of antibody titers to genotypes included in the vaccine was observed in 88-98% of subjects. Post-booster GMTs varied from 1666 to 4536 LU depending on genotype. These GMTs were 1.1 to 1.8-fold higher when compared to those observed one month post-second dose. After a booster of bHPV, a ≥4 fold increase of antibody titers to HPV16 and HPV18 was observed in 93-99% of subjects. The anti-HPV16 and HPV18 GMTs were 5458 and 2665 LU, respectively. These GMTs were 1.2 and 1.8 higher than those observed in the qHPV group (both P < 0.01). In bHPV group a 1.4-1.6-fold increase of antibody GMTs to HPV6 and HPV11was also observed (P < 0.001). The safety profile was acceptable for both vaccines. Both qHPV and bHPV increase antibody titers when given as a booster to girls previously vaccinated with 2 doses of qHPV. The magnitude of the immune response after booster is vaccine-dependent and has the same pattern as that reported after primary vaccination with qHPV or bHPV. When given as a booster, both vaccines have an acceptable safety profile. Longer follow-up studies are warranted to assess the need of booster doses.

Quality Improvement to Demonstrate the Lack of Reliability of the Human Papillomavirus mRNA Assay to Identify Women With Latent Human Papillomavirus Infections.

PubMed

Cotton, Sarah; Brown, Robert E; Nugent, Elizabeth K; Robazetti, Sonia C; Berens, Pamela D; Smith, Judith A

2018-04-01

To assess the consistency between human papillomavirus (HPV) mRNA testing in women with a history of previous HPV infections diagnosed by HPV DNA assay and the potential effects on follow-up HPV screening. This was a quality improvement study that used data from a pathology laboratory software database reviewed from November 2014 to June 2016 to identify female patients aged 30 years or older with greater than one HPV-positive result, including one or more HPV mRNA assay results and one or more documented HPV DNA assay results for comparison. Previous correlative cytology and colposcopic histopathology were also documented. American College of Obstetricians and Gynecologists' cervical cancer screening guidelines were used to compare potential differences in follow-up recommendations. Four hundred twenty-five charts for female patients 30 years of age or older were identified with one or more prior high-risk HPV infections by DNA assay. There was a 69.3% difference in HPV mRNA results compared with previous HPV DNA-positive results. There was a potential change in follow-up for 71.7% of patients with one prior high-risk-HPV-positive result and 60.0% of patients with two or more prior high-risk HPV-positive results. There were 231 colposcopy reports evaluated in this study. Of these, 62 (26.8%) were abnormal colposcopy reports, including 45 low-grade squamous intraepithelial lesions, 15 high-grade squamous intraepithelial lesions, and two cancers. Twenty-five (40.3%) abnormal colposcopy findings were in patients with a history of at least than two prior HPV DNA-positive results and a report of currently being HPV-negative with the mRNA assay. The HPV mRNA assays are less sensitive for detection of latent HPV infections compared with HPV DNA assays. Based on these data and the potential change in follow-up care, the HPV mRNA assay should not be used for a primary screening tool for cervical cancer. Many pathology laboratories have shifted to using the HPV mRNA assay without clear discussion with gynecologists about the effects on patient follow-up. The type of HPV assay being used should be documented and any HPV mRNA result confirmed by HPV DNA assay.

[High-risk HPV genotyping PCR testing as a means of cervical cancer and precancerous lesions early screening].

PubMed

Ma, Li; Cong, Xiao; Bian, Meilu; Shi, Mai; Wang, Xiuhong; Liu, Jun; Liu, Haiyan

2015-04-01

To explored high-risk HPV genotyping PCR testing whether as a feasible means for the early screening of cervical cancer and precancerous lesions. From January 2013 to June 2014, 15,192 outpatients in China-Japan Friendship Hospital voluntary were tested by high-risk type HPV genotyping PCR. The average age of them were (33±8) years old. High-risk HPV types genotyping PCR tested by fluorescence PCR technology, in which 13 kinds of high-risk HPV subtypes were detected, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68. A total of 4,315 cases of them were tested by the liquid-based cytology (LCT), among them with positive of high-risk HPV genotyping tested by PCR (n=2,366) were biopsy under colposcope (648 cases) in those LCT results were positive or LCT negative but HPV16 positive or LCT negative but had the clear clinical symptoms or and non-HPV16 positive but with clear clinical symptoms. (1) Analysis high-risk HPV infection status of 15 192 women. (2) As the pathological diagnosis was the gold standard in the diagnosis of cervical lesions, analysis of the relationship among high-risk HPV infection, virus loads and cervical lesions. (3) To evaluated the value of high-risk HPV genotyping PCR tested method in screening of cervical cancer and precancerous lesions. ⑴ Of 15,192 cases tested by high-risk HPV genotyping PCR, 2,366 cases were HPV positive (HPV infection), the overall infection rate was 15.57% (2,366/15,192), in which a single subtype of HPV infection in 1,767 cases, infection rate was 11.63% (1,767/15,192), and multiple subtypes of HPV infection (two and more subtypes HPV infection) in 599 cases, infection rate was 3.94% (599/15,192). The HPV16, 52 and 58 infections were the most common HPV subtypes in 13 subtypes, the infection rate was 3.95% (600/15,192), 2.86% (435/15,192) and 2.67% (406/15,192), respectively. (2) The most relevant subtypes with cervical intraepithelial neoplasia (CIN) II and even higher lesion were HPV16, 52 and 58, accounted for 57.7% (154/267) of all above CIN II lesions. The most relevant subtype with the cervical glandular intraepithelial neoplasia (CGIN) II or above lesions was HPV18, 3 cases with CGIN II or above lesions were all single HPV18 infection. The pathologic examination positive percentage of patients which HPV virus loads≤10(3) copys/10(4) cells was 18.2% (25/137), while the pathologic examination positive proportion was 33.3% (247/742) which HPV virus loads≥10(4) copys/10(4) cells, there was statistically significant difference between them (χ2=27.06, P=0.000). (3) Sensitivity, specificity, positive predictive value and negative predictive value for detection of CIN II or above using HPV genotyping PCR were 96.11%, 85.76%, 30.94% and 99.70%, respectively. There were a guiding significance for high-risk HPV genotyping PCR tested in screening of cervical cancer and precancerous lesion. HPV16, 52 and 58 were related to the severe cervical squamous epithelial lesions, while HPV18 was related to cervical severe glandular cell pathological changes. HPV genotyping is feasible and economical as the first choice of opportunistic screening in tertiary hospitals.

Degree-of-Freedom Strengthened Cascade Array for DOD-DOA Estimation in MIMO Array Systems.

PubMed

Yao, Bobin; Dong, Zhi; Zhang, Weile; Wang, Wei; Wu, Qisheng

2018-05-14

In spatial spectrum estimation, difference co-array can provide extra degrees-of-freedom (DOFs) for promoting parameter identifiability and parameter estimation accuracy. For the sake of acquiring as more DOFs as possible with a given number of physical sensors, we herein design a novel sensor array geometry named cascade array. This structure is generated by systematically connecting a uniform linear array (ULA) and a non-uniform linear array, and can provide more DOFs than some exist array structures but less than the upper-bound indicated by minimum redundant array (MRA). We further apply this cascade array into multiple input multiple output (MIMO) array systems, and propose a novel joint direction of departure (DOD) and direction of arrival (DOA) estimation algorithm, which is based on a reduced-dimensional weighted subspace fitting technique. The algorithm is angle auto-paired and computationally efficient. Theoretical analysis and numerical simulations prove the advantages and effectiveness of the proposed array structure and the related algorithm.

Proof-of-principle evaluation of the efficacy of fewer than three doses of a bivalent HPV16/18 vaccine.

PubMed

Kreimer, Aimée R; Rodriguez, Ana Cecilia; Hildesheim, Allan; Herrero, Rolando; Porras, Carolina; Schiffman, Mark; González, Paula; Solomon, Diane; Jiménez, Silvia; Schiller, John T; Lowy, Douglas R; Quint, Wim; Sherman, Mark E; Schussler, John; Wacholder, Sholom

2011-10-05

Three-dose regimens for human papillomavirus (HPV) vaccines are expensive and difficult to complete, especially in settings where the need for cervical cancer prevention is greatest. We evaluated the vaccine efficacy of fewer than three doses of the HPV16/18 vaccine Cervarix in our Costa Rica Vaccine Trial. Women were randomly assigned to receive three doses of the HPV16/18 vaccine or to a control vaccine and were followed for incident HPV16 or HPV18 infection that persisted in visits that were 10 or more months apart (median follow-up 4.2 years). After excluding women who had no follow-up or who were HPV16 and HPV18 DNA positive at enrollment, 5967 women received three vaccine doses (2957 HPV vaccine vs 3010 control vaccine), 802 received two doses (422 HPV vs. 380 control), and 384 received one dose (196 HPV vs. 188 control). Reasons for receiving fewer doses and other pre- and post-randomization characteristics were balanced within each dosage group between women receiving the HPV and control vaccines. Incident HPV16 or HPV18 infections that persisted for 1 year were unrelated to dosage of the control vaccine. Vaccine efficacy was 80.9% for three doses of the HPV vaccine (95% confidence interval [CI] = 71.1% to 87.7%; 25 and 133 events in the HPV and control arms, respectively), 84.1% for two doses (95% CI = 50.2% to 96.3%; 3 and 17 events), and 100% for one dose (95% CI = 66.5% to 100%; 0 and 10 events). Four years after vaccination of women who appeared to be uninfected, this nonrandomized analysis suggests that two doses of the HPV16/18 vaccine, and maybe even one dose, are as protective as three doses.

Natural history of anal human papillomavirus infection in heterosexual women and risks associated with persistence.

PubMed

Moscicki, Anna-Barbara; Ma, Yifei; Farhat, Sepideh; Jay, Julie; Hanson, Evelyn; Benningfield, Susanna; Jonte, Janet; Godwin-Medina, Cheryl; Wilson, Robert; Shiboski, Stephen

2014-03-01

Anal cancer is more common in women than in men, yet little is known about the natural history of human papillomavirus (HPV) in women. The objective was to examine the natural history of anal HPV in heterosexual women. Young women participating in an HPV cohort study were seen at 4-month intervals for cervical and anal HPV testing. Time to clearance was estimated using the Kaplan-Meier approach; risks for persistence were assessed using Cox regression models. Seventy-five women (mean age, 23.5 ± 4.1 years) who tested positive for anal HPV were followed for a mean of 84.5 ± 44.9 months. By 3 years, 82.5% of anal non-16 high-risk (HR) HPV, 82.6% of low-risk (LR) HPV, and 76.2% of HPV-16 infections had cleared. By 3 years, only 36.4% of women had become negative for all HPV types. In the multivariable model, concurrent cervical HPV-16 (P < .001), weekly alcohol use (P = .015), anal touching during sex (P = .045), recent anal sex (P = .04), and no condom use during anal sex (P = .04) were associated with HPV-16 persistence. Greater number of new sex partners (P = .024) and condom use during vaginal sex (P = .003) were associated with clearance. Similar associations were found for clearance in all HR-HPV infections. Only concomitant cervical HPV was associated with non-16 HR-HPV persistence. The majority of anal HPV infections cleared within 3 years. HPV-16 infections were slower to clear than other HR-HPV infections, consistent with its role in anal cancer. Specific sexual behaviors were associated with persistence, suggesting that education and behavioral interventions may decrease persistence.

Natural History of Anal Human Papillomavirus Infection in Heterosexual Women and Risks Associated With Persistence

PubMed Central

Moscicki, Anna-Barbara; Ma, Yifei; Farhat, Sepideh; Jay, Julie; Hanson, Evelyn; Benningfield, Susanna; Jonte, Janet; Godwin-Medina, Cheryl; Wilson, Robert; Shiboski, Stephen

2014-01-01

Background. Anal cancer is more common in women than in men, yet little is known about the natural history of human papillomavirus (HPV) in women. The objective was to examine the natural history of anal HPV in heterosexual women. Methods. Young women participating in an HPV cohort study were seen at 4-month intervals for cervical and anal HPV testing. Time to clearance was estimated using the Kaplan-Meier approach; risks for persistence were assessed using Cox regression models. Results. Seventy-five women (mean age, 23.5 ± 4.1 years) who tested positive for anal HPV were followed for a mean of 84.5 ± 44.9 months. By 3 years, 82.5% of anal non-16 high-risk (HR) HPV, 82.6% of low-risk (LR) HPV, and 76.2% of HPV-16 infections had cleared. By 3 years, only 36.4% of women had become negative for all HPV types. In the multivariable model, concurrent cervical HPV-16 (P < .001), weekly alcohol use (P = .015), anal touching during sex (P = .045), recent anal sex (P = .04), and no condom use during anal sex (P = .04) were associated with HPV-16 persistence. Greater number of new sex partners (P = .024) and condom use during vaginal sex (P = .003) were associated with clearance. Similar associations were found for clearance in all HR-HPV infections. Only concomitant cervical HPV was associated with non-16 HR-HPV persistence. Conclusions. The majority of anal HPV infections cleared within 3 years. HPV-16 infections were slower to clear than other HR-HPV infections, consistent with its role in anal cancer. Specific sexual behaviors were associated with persistence, suggesting that education and behavioral interventions may decrease persistence. PMID:24368624

Duration and clearance of anal human papillomavirus (HPV) infection among women: the Hawaii HPV cohort study.

PubMed

Shvetsov, Yurii B; Hernandez, Brenda Y; McDuffie, Katharine; Wilkens, Lynne R; Zhu, Xuemei; Ning, Lily; Killeen, Jeffrey; Kamemoto, Lori; Goodman, Marc T

2009-03-01

The association of anal cancer with human papillomavirus (HPV) infection is well established; however, little is known about the epidemiology of anal HPV in healthy women. We investigated patterns of duration and clearance of anal HPV infection in a cohort of healthy women in Hawaii. Viral and nonviral determinants of anal HPV clearance were examined in a longitudinal cohort study of 431 sexually active women. At baseline and at 4-month intervals, interviews were conducted and cervical and anal cell specimens were obtained for detection of HPV DNA. Of the 431 women, 50% experienced a total of 414 incident anal HPV infections, reported at 1 clinic visits from baseline through a follow-up period of average duration of 1.2 years. Of these infections, 58% cleared during follow-up. The clearance rate for a high-risk anal infection was 9.2 per 100 woman-months (95% confidence interval [CI], 6.9-11.9 per 100 woman-months), with a median duration of 150 days (95% CI, 132-243 days). The slowest clearing high-risk HPV types were HPV-59 (median clearance time, 350 days) and HPV-58 (median clearance time, 252 days). The median clearance times for HPV-16 and HPV-18, the predominant types associated with anal cancer, were 132 days and 212 days, respectively. Nonviral factors that delayed clearance of anal HPV included douching, long-term tobacco smoking, and anal sex. The majority of anal HPV infections resolve in a relatively short time. Although anal HPV is commonly acquired in healthy women, its rapid clearance suggests limited efficacy of HPV testing as an anal cancer screening tool.

A Cross-Sectional Study to Assess HPV Knowledge and HPV Vaccine Acceptability in Mali

PubMed Central

Poole, Danielle N.; Tracy, J. Kathleen; Levitz, Lauren; Rochas, Mali; Sangare, Kotou; Yekta, Shahla; Tounkara, Karamoko; Aboubacar, Ben; Koita, Ousmane; Lurie, Mark; De Groot, Anne S.

2013-01-01

Despite a high prevalence of oncogenic human papilloma virus (HPV) infection and cervical cancer mortality, HPV vaccination is not currently available in Mali. Knowledge of HPV and cervical cancer in Mali, and thereby vaccine readiness, may be limited. Research staff visited homes in a radial pattern from a central location to recruit adolescent females and males aged 12–17 years and men and women aged ≥18 years (N = 51) in a peri-urban village of Bamako, Mali. Participants took part in structured interviews assessing knowledge, attitudes, and practices related to HPV, cervical cancer, and HPV vaccination. We found low levels of HPV and cervical cancer knowledge. While only 2.0% of respondents knew that HPV is a sexually transmitted infection (STI), 100% said they would be willing to receive HPV vaccination and would like the HPV vaccine to be available in Mali. Moreover, 74.5% said they would vaccinate their child(ren) against HPV. Men were found to have significantly greater autonomy in the decision to vaccinate themselves than women and adolescents (p = 0.005), a potential barrier to be addressed by immunization campaigns. HPV vaccination would be highly acceptable if the vaccine became widely available in Bamako, Mali. This study demonstrates the need for a significant investment in health education if truly informed consent is to be obtained for HPV vaccination. Potential HPV vaccination campaigns should provide more information about HPV and the vaccine. Barriers to vaccination, including the significantly lower ability of the majority of the target population to autonomously decide to get vaccinated, must also be addressed in future HPV vaccine campaigns. PMID:23431375

A cross-sectional study to assess HPV knowledge and HPV vaccine acceptability in Mali.

PubMed

Poole, Danielle N; Tracy, J Kathleen; Levitz, Lauren; Rochas, Mali; Sangare, Kotou; Yekta, Shahla; Tounkara, Karamoko; Aboubacar, Ben; Koita, Ousmane; Lurie, Mark; De Groot, Anne S

2013-01-01

Despite a high prevalence of oncogenic human papilloma virus (HPV) infection and cervical cancer mortality, HPV vaccination is not currently available in Mali. Knowledge of HPV and cervical cancer in Mali, and thereby vaccine readiness, may be limited. Research staff visited homes in a radial pattern from a central location to recruit adolescent females and males aged 12-17 years and men and women aged ≥ 18 years (N = 51) in a peri-urban village of Bamako, Mali. Participants took part in structured interviews assessing knowledge, attitudes, and practices related to HPV, cervical cancer, and HPV vaccination. We found low levels of HPV and cervical cancer knowledge. While only 2.0% of respondents knew that HPV is a sexually transmitted infection (STI), 100% said they would be willing to receive HPV vaccination and would like the HPV vaccine to be available in Mali. Moreover, 74.5% said they would vaccinate their child(ren) against HPV. Men were found to have significantly greater autonomy in the decision to vaccinate themselves than women and adolescents (p = 0.005), a potential barrier to be addressed by immunization campaigns. HPV vaccination would be highly acceptable if the vaccine became widely available in Bamako, Mali. This study demonstrates the need for a significant investment in health education if truly informed consent is to be obtained for HPV vaccination. Potential HPV vaccination campaigns should provide more information about HPV and the vaccine. Barriers to vaccination, including the significantly lower ability of the majority of the target population to autonomously decide to get vaccinated, must also be addressed in future HPV vaccine campaigns.

Prevalence of the integration status for human papillomavirus 16 in esophageal carcinoma samples.

PubMed

Li, Shuying; Shen, Haie; Li, Ji; Hou, Xiaoli; Zhang, Ke; Li, Jintao

2018-03-01

To investigate the etiology of esophageal cancer (EC) related with human papillomavirus (HPV) infection. Fresh surgically resected tissue samples and clinical information were obtained from 189 patients. Genomic DNA was extracted, and HPV was detected using polymerase chain reaction (PCR) with HPV L1 gene primers of MY09/11; HPV16 was detected using HPV16 E6 type-specific primer sets. Copies of HPV16 E2, E6, and the human housekeeping gene β-actin were tested using quantitative PCR to analyze the relationship between HPV16 integration and esophageal squamous cell carcinoma and the relationship between the HPV16 integration status and clinical information of patients. Of the 189 samples, 168 HPV-positive samples were detected, of which 76 were HPV16 positive. Among the HPV16 positive samples, 2 cases (E2/E6 ratio>1) were 2.6% (2/76) purely episomal, 65 (E2/E6 ratio between 0 and 1) were 85.6% (65/76) mixture of integrated and episomal, and 9 (E2/E6 ratio=0) were 11.8% (9/76) purely integrated. The results indicate that integration of HPV16 was more common in the host genome than in the episome genome. The prevalence rate of HPV16 integration is increasing with the pathological stage progression of esophageal carcinoma (EC). A high prevalence of HPV16 suggested that HPV16 has an etiological effect on the progress of EC. Integration of HPV16 is more common than episome genome in the host cells, indicating that continuous HPV infection is the key to esophageal epithelial cell malignant conversion and canceration.

Human Papilloma Virus Infection Does Not Predict Response to Interferon Therapy in Ocular Surface Squamous Neoplasia.

PubMed

Galor, Anat; Garg, Nisha; Nanji, Afshan; Joag, Madhura; Nuovo, Gerard; Palioura, Sotiria; Wang, Gaofeng; Karp, Carol L

2015-11-01

To identify the frequency of human papilloma virus (HPV) in ocular surface squamous neoplasia (OSSN) and to evaluate differences in clinical features and treatment response of tumors with positive versus negative HPV results. Retrospective case series. Twenty-seven patients with OSSN. Ocular surface squamous neoplasia specimens were analyzed for the presence of HPV. Clinical features and response to interferon were determined retrospectively and linked to the presence (versus absence) of HPV. Clinical characteristics of OSSN by HPV status. Twenty-one of 27 tumors (78%) demonstrated positive HPV results. The HPV genotypes identified included HPV-16 in 10 tumors (48%), HPV-31 in 5 tumors, HPV-33 in 1 tumor, HPV-35 in 2 tumors, HPV-51 in 2 tumors, and a novel HPV in 3 tumors (total of 23 tumors because 1 tumor had 3 identified genotypes). Tumors found in the superior limbus were more likely to show positive HPV results (48% vs. 0%; P=0.06, Fisher exact test). Tumors with positive HPV-16 results were larger (68 vs. 34 mm2; P=0.08, Mann-Whitney U test) and were more likely to have papillomatous morphologic features (50% vs. 12%; P=0.07, Fisher exact test) compared with tumors showing negative results for HPV-16. Human papilloma virus status was not found to be associated with response to interferon therapy (P=1.0, Fisher exact test). Metrics found to be associated with a nonfavorable response to interferon were male gender and tumors located in the superior conjunctivae. The presence of HPV in OSSN seems to be more common in lesions located in the nonexposed, superior limbus. Human papilloma virus presence does not seem to be required for a favorable response to interferon therapy. Copyright © 2015 American Academy of Ophthalmology. All rights reserved.

Awareness and Knowledge Levels of Turkish College Students about Human Papilloma Virus Infection and Vaccine Acceptance.

PubMed

Oz, Murat; Cetinkaya, Nilufer; Apaydin, Aysen; Korkmaz, Elmas; Bas, Sevda; Ozgu, Emre; Gungor, Tayfun

2018-04-01

Awareness of HPV by the target population is an important determinant of vaccine acceptance. The aim of this study is to evaluate the awareness of HPV infection and acceptability of the HPV vaccines among Turkish college students. College students aged 18-30 who were attending a large public university in Ankara participated in this study. The participants were asked to complete a questionnaire to elicit demographic characteristics, awareness level of HPV and HPV vaccine, and willingness to be vaccinated. One thousand one hundred sixty students responded to the invitation email and completed the questionnaire. The mean scores of female students about HPV and HPV vaccine were 7.1/15 and 3.6/9, respectively, while these scores were 7.9/15 and 3.4/9 among male students, respectively. While 51 % percent of female and 33.5 % of male students had heard of HPV and 32.8 % and 18 % of them had heard of HPV vaccine, respectively, only 1.5 % of female and 0.4 % of male students had been vaccinated against HPV. A total of 507 students (43.7 %) had previously heard of HPV. Only 309 (26.6 %) of the participants had previously heard of the HPV vaccine, and 45.1 % of the students were willing to receive HPV vaccination. The main predictors for willingness to be vaccinated were the following: sexual experience, sexual behavior, past history of sexually transmitted infection (STI), and knowledge about HPV and HPV vaccine. Higher awareness levels of HPV and HPV vaccine are significantly related to greater willingness to be vaccinated, and the main reasons for rejecting the vaccine were insufficient information about the vaccine and possible unknown side effects.

Human papillomavirus in upper digestive tract tumors from three countries

PubMed Central

Castillo, Andres; Koriyama, Chihaya; Higashi, Michiyo; Anwar, Muhammad; Bukhari, Mulazim Hussain; Carrascal, Edwin; Mancilla, Lida; Okumura, Hiroshi; Matsumoto, Masataka; Sugihara, Kazumasa; Natsugoe, Shoji; Eizuru, Yoshito; Akiba, Suminori

2011-01-01

AIM: To clarify human papillomavirus (HPV) involvement in carcinogenesis of the upper digestive tract of virological and pathological analyses. METHODS: The present study examined the presence of HPV in squamous cell carcinomas of the oral cavity (n = 71), and esophagus (n = 166) collected from Japan, Pakistan and Colombia, with different HPV exposure risk and genetic backgrounds. The viral load and physical status of HPV16 and HPV16-E6 variants were examined. Comparison of p53 and p16INK4a expression in HPV-positive and HPV-negative cases was also made. RESULTS: HPV16 was found in 39 (55%) oral carcinomas (OCs) and 24 (14%) esophageal carcinomas (ECs). This site-specific difference in HPV detection between OCs and ECs was statistically significant (P < 0.001). There was a significant difference in the geographical distribution of HPV16-E6 variants. Multiple infections of different HPV types were found in 13 ECs, but multiple infections were not found in OCs. This difference was statistically significant (P = 0.001). The geometric means (95% confidence interval) of HPV16 viral load in OCs and ECs were 0.06 (0.02-0.18) and 0.12 (0.05-0.27) copies per cell, respectively. The expression of p16INK4a proteins was increased by the presence of HPV in ECs (53% and 33% in HPV-positive and -negative ECs, respectively; P = 0.036), and the high-risk type of the HPV genome was not detected in surrounding normal esophageal mucosa of HPV-positive ECs. CONCLUSION: Based on our results, we cannot deny the possibility of HPV16 involvement in the carcinogenesis of the esophagus. PMID:22219599

Very high frequency (beyond 100 MHz) PZT kerfless linear arrays.

PubMed

Wu, Da-Wei; Zhou, Qifa; Geng, Xuecang; Liu, Chang-Geng; Djuth, Frank; Shung, K Kirk

2009-10-01

This paper presents the design, fabrication, and measurements of very high frequency kerfless linear arrays prepared from PZT film and PZT bulk material. A 12-microm PZT thick film fabricated from PZT-5H powder/solution composite and a piece of 15-microm PZT-5H sheet were used to fabricate 32-element kerfless high-frequency linear arrays with photolithography. The PZT thick film was prepared by spin-coating of PZT sol-gel composite solution. The thin PZT-5H sheet sample was prepared by lapping a PZT-5H ceramic with a precision lapping machine. The measured results of the 2 arrays were compared. The PZT film array had a center frequency of 120 MHz, a bandwidth of 60% with a parylene matching layer, and an insertion loss of 41 dB. The PZT ceramic sheet array was found to have a center frequency of 128 MHz with a poorer bandwidth (40% with a parylene matching layer) but a better sensitivity (28 dB insertion loss).

Very High Frequency (Beyond 100 MHz) PZT Kerfless Linear Arrays

PubMed Central

Wu, Da-Wei; Zhou, Qifa; Geng, Xuecang; Liu, Chang-Geng; Djuth, Frank; Shung, K. Kirk

2010-01-01

This paper presents the design, fabrication, and measurements of very high frequency kerfless linear arrays prepared from PZT film and PZT bulk material. A 12-µm PZT thick film fabricated from PZT-5H powder/solution composite and a piece of 15-µm PZT-5H sheet were used to fabricate 32-element kerfless high-frequency linear arrays with photolithography. The PZT thick film was prepared by spin-coating of PZT sol-gel composite solution. The thin PZT-5H sheet sample was prepared by lapping a PZT-5H ceramic with a precision lapping machine. The measured results of the 2 arrays were compared. The PZT film array had a center frequency of 120 MHz, a bandwidth of 60% with a parylene matching layer, and an insertion loss of 41 dB. The PZT ceramic sheet array was found to have a center frequency of 128 MHz with a poorer bandwidth (40% with a parylene matching layer) but a better sensitivity (28 dB insertion loss). PMID:19942516

Sparse array angle estimation using reduced-dimension ESPRIT-MUSIC in MIMO radar.

PubMed

Zhang, Chaozhu; Pang, Yucai

2013-01-01

Sparse linear arrays provide better performance than the filled linear arrays in terms of angle estimation and resolution with reduced size and low cost. However, they are subject to manifold ambiguity. In this paper, both the transmit array and receive array are sparse linear arrays in the bistatic MIMO radar. Firstly, we present an ESPRIT-MUSIC method in which ESPRIT algorithm is used to obtain ambiguous angle estimates. The disambiguation algorithm uses MUSIC-based procedure to identify the true direction cosine estimate from a set of ambiguous candidate estimates. The paired transmit angle and receive angle can be estimated and the manifold ambiguity can be solved. However, the proposed algorithm has high computational complexity due to the requirement of two-dimension search. Further, the Reduced-Dimension ESPRIT-MUSIC (RD-ESPRIT-MUSIC) is proposed to reduce the complexity of the algorithm. And the RD-ESPRIT-MUSIC only demands one-dimension search. Simulation results demonstrate the effectiveness of the method.

Extraction and Propagation of an Intense Rotating Electron Beam,

DTIC Science & Technology

1982-10-01

radiochromic foils positioned at z = 25 cm. The equal transmission density contours are ranked in linear order of increasing exposure (increasing current...flux encircled by the cathode e = %rc2Bc. Linearizing the equation of motion around the equilibrium, we can find the wavelength of small radial...the beam rotation. The mask which precedes the scint- illator is a linear array of dots while the projection is made up of two disjoint linear arrays

Prevalence of Human Papilloma Virus in Sinonasal Papilloma in Southern Iranian Population

PubMed Central

Valibeigi, Behnaz; Ashraf, Mohamad Javad; Kerdegari, Narges; Safai, Akbar; Abedi, Elham; Khademi, Bijan; Azarpira, Negar

2017-01-01

Statement of the Problem: Sinonasal papilloma (SNP) is a rare benign lesion characterized by high recurrence rate and malignant transformation. Purpose: This study aimed to investigate the prevalence of human papilloma virus (HPV) infection in these lesions in South of Iran. Materials and Method: In this cross sectional retrospective study, a total of 41 patients, 38 SNP and 3 SNP/Squamous cell carcinoma cases, from 2007 to 2014 were studied. Human papilloma virus (HPV) DNA detection was performed by nested PCR method and positive cases were analyzed for high risk HPV-16 and HPV-18. Results: HPV was detected in 31.7%; HPV- 16 in 4.9% and HPV 18 was not detected at all. Dysplastic epithelium was detected in 53% that was not associated with HPV. Three cases were accompanied with malignant transformation that HPV genome was detected in only one case and none of them were positive for HPV16 /18 genomic DNA. Conclusion: Current research suggests that HPV may be involved in the development of SNP. But the high risk HPV is not important in malignant transformation. More studies are needed to elucidate the possible etiologic mechanism between HPV, inverted papilloma, and squamous cell carcinoma. PMID:28620639

Prevalence of Human Papilloma Virus in Sinonasal Papilloma in Southern Iranian Population.

PubMed

Valibeigi, Behnaz; Ashraf, Mohamad Javad; Kerdegari, Narges; Safai, Akbar; Abedi, Elham; Khademi, Bijan; Azarpira, Negar

2017-06-01

Sinonasal papilloma (SNP) is a rare benign lesion characterized by high recurrence rate and malignant transformation. This study aimed to investigate the prevalence of human papilloma virus (HPV) infection in these lesions in South of Iran. In this cross sectional retrospective study, a total of 41 patients, 38 SNP and 3 SNP/Squamous cell carcinoma cases, from 2007 to 2014 were studied. Human papilloma virus (HPV) DNA detection was performed by nested PCR method and positive cases were analyzed for high risk HPV-16 and HPV-18. HPV was detected in 31.7%; HPV- 16 in 4.9% and HPV 18 was not detected at all. Dysplastic epithelium was detected in 53% that was not associated with HPV. Three cases were accompanied with malignant transformation that HPV genome was detected in only one case and none of them were positive for HPV16 /18 genomic DNA. Current research suggests that HPV may be involved in the development of SNP. But the high risk HPV is not important in malignant transformation. More studies are needed to elucidate the possible etiologic mechanism between HPV, inverted papilloma, and squamous cell carcinoma.

Radiosensitivity and effect of hypoxia in HPV positive head and neck cancer cells.

PubMed

Sørensen, Brita Singers; Busk, Morten; Olthof, Nadine; Speel, Ernst-Jan; Horsman, Michael R; Alsner, Jan; Overgaard, Jens

2013-09-01

HPV associated Head and Neck Squamous Cell Carcinoma (HNSCC) represents a distinct subgroup of HNSCC characterized by a favorable prognosis and a distinct molecular biology. Previous data from the randomized DAHANCA 5 trial indicated that HPV positive tumors did not benefit from hypoxic modifications by Nimorazole during radiotherapy, whereas a significant benefit was observed in the HPV negative tumors. However, more studies have demonstrated equal frequencies of hypoxic tumors among HPV-positive and HPV-negative tumors. The aim of the present study was to determine radiosensitivity, the impact of hypoxia and the effect of Nimorazole in HPV positive and HPV negative cell lines. The used cell lines were: UDSCC2, UMSCC47 and UPCISCC90 (HPV positive) and FaDuDD, UTSCC33 and UTSCC5 (HPV negative). Cells were cultured under normoxic or hypoxic conditions, and gene expression levels of previously established hypoxia induced genes were assessed by qPCR. Cells were irradiated with various doses under normoxia, hypoxia or hypoxia +1mM Nimorazole, and the clonogenic survival was determined. The HPV positive and HPV negative cell lines exhibited similar patterns of upregulation of hypoxia induced genes in response to hypoxia. The HPV positive cell lines were up to 2.4 times more radiation sensitive than HPV negative cell lines. However, all HPV positive cells displayed the same response to hypoxia in radiosensitivity, with an OER in the range 2.3-2.9, and a sensitizer effect of Nimorazole of 1.13-1.29, similar to HPV negative cells. Although HPV positive cells had a markedly higher radiosensitivity compared to HPV negative cells, they displayed the same relative radioresistance under hypoxia and the same relative sensitizer effect of Nimorazole. The clinical observation that HPV positive patients do not seem to benefit from Nimorazole treatment is not due to inherent differences in hypoxia sensitivity or response to Nimorazole, but can be accounted for by the overall higher radiosensitivity of HPV positive cells. Copyright © 2013. Published by Elsevier Ireland Ltd.

Biological relevance of human papillomaviruses in vulvar cancer.

PubMed

Halec, Gordana; Alemany, Laia; Quiros, Beatriz; Clavero, Omar; Höfler, Daniela; Alejo, Maria; Quint, Wim; Pawlita, Michael; Bosch, Francesc X; de Sanjose, Silvia

2017-04-01

The carcinogenic role of high-risk human papillomavirus (HR-HPV) types in the increasing subset of vulvar intraepithelial neoplasia and vulvar cancer in young women has been established. However, the actual number of vulvar cancer cases attributed to HPV is still imprecisely defined. In an attempt to provide a more precise definition of HPV-driven vulvar cancer, we performed HPV-type-specific E6*I mRNA analyses available for 20 HR-/possible HR (pHR)-HPV types, on tissue samples from 447 cases of vulvar cancer. HPV DNA genotyping was performed using SPF10-LiPA 25 assay due to its high sensitivity in formalin-fixed paraffin-embedded tissues. Data on p16 INK4a expression was available for comparative analysis via kappa statistics. The use of highly sensitive assays covering the detection of HPV mRNA in a broad spectrum of mucosal HPV types resulted in the detection of viral transcripts in 87% of HPV DNA+ vulvar cancers. Overall concordance between HPV mRNA+ and p16 INK4a upregulation (strong, diffuse immunostaining in >25% of tumor cells) was 92% (K=0.625, 95% confidence interval (CI)=0.531-0.719). Among these cases, 83% were concordant pairs of HPV mRNA+ and p16 INK4a + and 9% were concordant pairs of HPV mRNA- and p16 INK4a -. Our data confirm the biological role of HR-/pHR-HPV types in the great majority of HPV DNA+ vulvar cancers, resulting in an HPV-attributable fraction of at least 21% worldwide. Most HPV DNA+ vulvar cancers were associated with HPV16 (85%), but a causative role for other, less frequently occurring mucosal HPV types (HPV26, 66, 67, 68, 70 and 73) was also confirmed at the mRNA level for the first time. These findings should be taken into consideration for future screening options as HPV-associated vulvar preneoplastic lesions have increased in incidence in younger women and require different treatment than vulvar lesions that develop from rare autoimmune-related mechanisms in older women.

Transitional probability-based model for HPV clearance in HIV-1-positive adolescent females.

PubMed

Kravchenko, Julia; Akushevich, Igor; Sudenga, Staci L; Wilson, Craig M; Levitan, Emily B; Shrestha, Sadeep

2012-01-01

HIV-1-positive patients clear the human papillomavirus (HPV) infection less frequently than HIV-1-negative. Datasets for estimating HPV clearance probability often have irregular measurements of HPV status and risk factors. A new transitional probability-based model for estimation of probability of HPV clearance was developed to fully incorporate information on HIV-1-related clinical data, such as CD4 counts, HIV-1 viral load (VL), highly active antiretroviral therapy (HAART), and risk factors (measured quarterly), and HPV infection status (measured at 6-month intervals). Data from 266 HIV-1-positive and 134 at-risk HIV-1-negative adolescent females from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort were used in this study. First, the associations were evaluated using the Cox proportional hazard model, and the variables that demonstrated significant effects on HPV clearance were included in transitional probability models. The new model established the efficacy of CD4 cell counts as a main clearance predictor for all type-specific HPV phylogenetic groups. The 3-month probability of HPV clearance in HIV-1-infected patients significantly increased with increasing CD4 counts for HPV16/16-like (p<0.001), HPV18/18-like (p<0.001), HPV56/56-like (p = 0.05), and low-risk HPV (p<0.001) phylogenetic groups, with the lowest probability found for HPV16/16-like infections (21.60±1.81% at CD4 level 200 cells/mm(3), p<0.05; and 28.03±1.47% at CD4 level 500 cells/mm(3)). HIV-1 VL was a significant predictor for clearance of low-risk HPV infections (p<0.05). HAART (with protease inhibitor) was significant predictor of probability of HPV16 clearance (p<0.05). HPV16/16-like and HPV18/18-like groups showed heterogeneity (p<0.05) in terms of how CD4 counts, HIV VL, and HAART affected probability of clearance of each HPV infection. This new model predicts the 3-month probability of HPV infection clearance based on CD4 cell counts and other HIV-1-related clinical measurements.

Double positivity for HPV-DNA/p16ink4a is the biomarker with strongest diagnostic accuracy and prognostic value for human papillomavirus related oropharyngeal cancer patients.

PubMed

Mena, Marisa; Taberna, Miren; Tous, Sara; Marquez, Sandra; Clavero, Omar; Quiros, Beatriz; Lloveras, Belen; Alejo, Maria; Leon, Xavier; Quer, Miquel; Bagué, Silvia; Mesia, Ricard; Nogués, Julio; Gomà, Montserrat; Aguila, Anton; Bonfill, Teresa; Blazquez, Carmen; Guix, Marta; Hijano, Rafael; Torres, Montserrat; Holzinger, Dana; Pawlita, Michael; Pavon, Miguel Angel; Bravo, Ignacio G; de Sanjosé, Silvia; Bosch, Francesc Xavier; Alemany, Laia

2018-03-01

The etiologic role of human papillomaviruses (HPV) in oropharyngeal cancer (OPC) is well established. Nevertheless, information on survival differences by anatomic sub-site or treatment remains scarce, and it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value. We conducted a retrospective cohort study of all patients diagnosed with a primary OPC in four Catalonian hospitals from 1990 to 2013. Formalin-fixed, paraffin-embedded cancer tissues were subjected to histopathological evaluation, DNA quality control, HPV-DNA detection, and p16 INK4a /pRb/p53/Cyclin-D1 immunohistochemistry. HPV-DNA positive and a random sample of HPV-DNA negative cases were subjected to HPV-E6*I mRNA detection. Demographic, tobacco/alcohol use, clinical and follow-up data were collected. Multivariate models were used to evaluate factors associated with HPV positivity as defined by four different HPV-relatedness definitions. Proportional-hazards models were used to compare the risk of death and recurrence among HPV-related and non-related OPC. 788 patients yielded a valid HPV-DNA result. The percentage of positive cases was 10.9%, 10.2%, 8.5% and 7.4% for p16 INK4a , HPV-DNA, HPV-DNA/HPV-E6*I mRNA, and HPV-DNA/p16 INK4a , respectively. Being non-smoker or non-drinker was consistently associated across HPV-relatedness definitions with HPV positivity. A suggestion of survival differences between anatomic sub-sites and treatments was observed. Double positivity for HPV-DNA/p16 INK4a showed strongest diagnostic accuracy and prognostic value. Double positivity for HPV-DNA/p16 INK4a , a test that can be easily implemented in the clinical practice, has optimal diagnostic accuracy and prognostic value. Our results have strong clinical implications for patients' classification and handling and also suggest that not all the HPV-related OPC behave similarly. Copyright © 2018 Elsevier Ltd. All rights reserved.

Chlamydia trachomatis prevalence and chlamydial/HPV co-infection among HPV-unvaccinated young Italian females with normal cytology.

PubMed

Panatto, Donatella; Amicizia, Daniela; Bianchi, Silvia; Frati, Elena Rosanna; Zotti, Carla Maria; Lai, Piero Luigi; Domnich, Alexander; Colzani, Daniela; Gasparini, Roberto; Tanzi, Elisabetta

2015-01-01

Infections caused by Chlamydia trachomatis (Ct) and human papillomavirus (HPV) are the two main sexually transmitted infections; however, epidemiological data on Ct prevalence and Ct/HPV co-infection in Italy are scant. This study aimed at estimating the prevalence of Ct infection and Ct/HPV co-infection in young HPV-unvaccinated females with normal cytology, and placed particular attention on the possible association between Ct-DNA positivity and different HPV infecting genotypes. Five hundred 66 healthy females aged 16-26 years without cervical lesions, previously assessed for HPV infection (HPV-DNA prevalence: 18.2%), were tested for Ct-DNA. The overall prevalence of Ct was 5.8% (95% CI: 4.2-8.1), while Ct/HPV co-infection was recorded in 2.7% (95% CI: 1.6-4.3) of subjects. Compared with HPV-DNA-negative females, HPV-DNA positive subjects had significantly (P < 0.001) higher odds of being infected with Ct (odds ratio of 4.20, 95% CI: 2.01-8.71). Both Ct and Ct/HPV infections were much more prevalent in under 18-year-olds than in older women. Subjects positive for single high-risk HPV genotypes and various multiple HPV infections had higher odds of being Ct-DNA positive. Our findings confirm that HPV and Ct infections are very common among asymptomatic young Italian females. This underlines the urgent need for nationwide Ct screening programs and reinforcement of sexual health education, which would be the most important public health strategies, since no Ct vaccines are currently available.

HPV vaccine acceptability in HIV-infected and HIV negative men who have sex with men (MSM) in Ireland.

PubMed

Sadlier, C; Lynam, A; O'Dea, S; Delamere, S; Quinlan, M; Clarke, S; Sheils, O; Bergin, C

2016-06-02

Background Men who have sex with men (MSM), particularly HIV-infected MSM are disproportionately affected by HPV infection and associated disease. The HPV vaccine has potential to greatly reduce the burden of HPV-associated disease including anal cancer in MSM. The efficacy of the HPV vaccine is dependent on high levels of vaccine uptake. The aim of this study was to examine HPV vaccine acceptability and factors influencing vaccine acceptability in MSM in Ireland. Methods A self-administered survey was distributed to HIV-infected and HIV negative MSM examining HPV vaccine acceptability and factors associated with vaccine acceptability. Logistic regression was used to identify key variables and predictors of HPV vaccine acceptability. Results 302 MSM participated in the study. Acceptability of HPV vaccine was 31% (unconditional), 51% (conditional on stated efficacy and a cost of €300), 65% (conditional on stated efficacy and a cost of €100) and 78% (conditional on stated efficacy and no cost). Cost was negatively associated with HPV vaccine acceptability (p<0.01) while knowledge of HPV vaccine efficacy was significantly associated with vaccine acceptability, even in the context of associated cost (p<0.01). Conclusions Acceptability of HPV vaccine in MSM in Ireland is high based on no cost vaccine and on stated vaccine efficacy (78%). Cost is negatively associated with vaccine acceptability. Understanding levels of knowledge of HPV infection, HPV associated disease and attitudes toward HPV vaccination are important as they will contribute to HPV vaccine acceptability among MSM and will help guide effective preventive programs.

HPV vaccine acceptability in HIV-infected and HIV negative men who have sex with men (MSM) in Ireland

PubMed Central

Sadlier, C.; Lynam, A.; O'Dea, S.; Delamere, S.; Quinlan, M.; Clarke, S.; Sheils, O.; Bergin, C.

2016-01-01

ABSTRACT Background Men who have sex with men (MSM), particularly HIV-infected MSM are disproportionately affected by HPV infection and associated disease. The HPV vaccine has potential to greatly reduce the burden of HPV-associated disease including anal cancer in MSM. The efficacy of the HPV vaccine is dependent on high levels of vaccine uptake. The aim of this study was to examine HPV vaccine acceptability and factors influencing vaccine acceptability in MSM in Ireland. Methods A self-administered survey was distributed to HIV-infected and HIV negative MSM examining HPV vaccine acceptability and factors associated with vaccine acceptability. Logistic regression was used to identify key variables and predictors of HPV vaccine acceptability. Results 302 MSM participated in the study. Acceptability of HPV vaccine was 31% (unconditional), 51% (conditional on stated efficacy and a cost of €300), 65% (conditional on stated efficacy and a cost of €100) and 78% (conditional on stated efficacy and no cost). Cost was negatively associated with HPV vaccine acceptability (p<0.01) while knowledge of HPV vaccine efficacy was significantly associated with vaccine acceptability, even in the context of associated cost (p<0.01). Conclusions Acceptability of HPV vaccine in MSM in Ireland is high based on no cost vaccine and on stated vaccine efficacy (78%). Cost is negatively associated with vaccine acceptability. Understanding levels of knowledge of HPV infection, HPV associated disease and attitudes toward HPV vaccination are important as they will contribute to HPV vaccine acceptability among MSM and will help guide effective preventive programs. PMID:27153289

Detection of human papillomavirus 16, 18, and 45 in women with ASC-US cytology and the risk of cervical precancer: results from the CLEAR HPV study.

PubMed

Castle, Phillip E; Cuzick, Jack; Stoler, Mark H; Wright, Thomas C; Reid, Jennifer L; Dockter, Janel; Giachetti, Cristina; Getman, Damon

2015-02-01

The Aptima human papillomavirus (HPV) 16 18/45 Genotype (GT) assay (AHPV-GT) is a qualitative E6/ E7 oncogene messenger RNA test that detects HPV 16 and a pool of HPV 18 and 45. The CLEAR (Clinical Evaluation of APTIMA mRNA) study was the pivotal, prospective, multicenter US clinical study to validate the Aptima HPV (AHPV) assays. In this analysis, we evaluated the clinical performance of AHPV and AHPV-GT assays for detection of cervical intraepithelial neoplasia grade 2 or more severe (CIN2 +) and grade 3 (CIN3) or adenocarcinoma in situ in 912 women with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou result. The AHPV-GT assay was performed on high-risk HPV (hrHPV) positives as determined by the AHPV assay. Overall, the percent positive for hrHPV was 38.8% (354/912), of which 34.2% (121/354) were GT positive. Among hrHPV-positive women, the risks of CIN2 + were 37.0% for HPV 16 positives, 15.9% for HPV 18/45 positives, 14.3% for other hrHPV positives, and 2.2% for AHPV negatives. The risks of CIN3 + were 20.5% for HPV 16 positives, 9.1% for HPV 18/45 positives, 4.3% for other hrHPV positives, and 0.7% for HPV negatives. We demonstrated that AHPV-GT is a reliable and effective test for cervical cancer risk stratification in women with an ASC-US cytology diagnosis. Copyright© by the American Society for Clinical Pathology.

Epidemiology of HPV Genotypes among HIV Positive Women in Kenya: A Systematic Review and Meta-Analysis.

PubMed

Menon, Sonia; Wusiman, Aibibula; Boily, Marie Claude; Kariisa, Mbabazi; Mabeya, Hillary; Luchters, Stanley; Forland, Frode; Rossi, Rodolfo; Callens, Steven; Vanden Broeck, Davy

2016-01-01

There is a scarcity of data on the distribution of human papillomavirus (HPV) genotypes in the HIV positive population and in invasive cervical cancer (ICC) in Kenya. This may be different from genotypes found in abnormal cytology. Yet, with the advent of preventive HPV vaccines that target HPV 16 and 18, and the nonavalent vaccine targeting 90% of all ICC cases, such HPV genotype distribution data are indispensable for predicting the impact of vaccination and HPV screening on prevention. Even with a successful vaccination program, vaccinated women will still require screening to detect those who will develop ICC from other High risk (HR) HPV genotypes not prevented by current vaccines. The aim of this review is to report on the prevalence of pHR/HR HPV types and multiple pHR/HR HPV genotypes in Kenya among HIV positive women with normal, abnormal cytology and ICC. PUBMED, EMBASE, SCOPUS, and PROQUEST were searched for articles on HPV infection up to August 2nd 2016. Search terms were HIV, HPV, Cervical Cancer, Incidence or Prevalence, and Kenya. The 13 studies included yielded a total of 2116 HIV-infected women, of which 89 had ICC. The overall prevalence of pHR/HR HPV genotypes among HIV-infected women was 64% (95%CI: 50%-77%). There was a borderline significant difference in the prevalence of pHR/HR HPV genotypes between Female Sex workers (FSW) compared to non-FSW in women with both normal and abnormal cytology. Multiple pHR/HR HPV genotypes were highly prominent in both normal cytology/HSIL and ICC. The most prevalent HR HPV genotypes in women with abnormal cytology were HPV 16 with 26%, (95%CI: 23.0%-30.0%) followed by HPV 35 and 52, with 21% (95%CI: 18%-25%) and 18% (95%CI: 15%-21%), respectively. In women with ICC, the most prevalent HPV genotypes were HPV 16 (37%; 95%CI: 28%-47%) and HPV 18 (24%; 95%CI: 16%-33%). HPV 16/18 gains prominence as the severity of cervical disease increases, with HPV 16/18 accounting for 61% (95%CI: 50.0%-70.0%) of all ICC cases. A secondary prevention program will be necessary as this population harbors multiple pHR/HR HPV co-infections, which may not be covered by current vaccines. A triage based on FSW as an indicator may be warranted.

Epidemiology of HPV Genotypes among HIV Positive Women in Kenya: A Systematic Review and Meta-Analysis

PubMed Central

Menon, Sonia; Wusiman, Aibibula; Boily, Marie Claude; Kariisa, Mbabazi; Mabeya, Hillary; Luchters, Stanley; Forland, Frode; Rossi, Rodolfo; Callens, Steven; vanden Broeck, Davy

2016-01-01

Background There is a scarcity of data on the distribution of human papillomavirus (HPV) genotypes in the HIV positive population and in invasive cervical cancer (ICC) in Kenya. This may be different from genotypes found in abnormal cytology. Yet, with the advent of preventive HPV vaccines that target HPV 16 and 18, and the nonavalent vaccine targeting 90% of all ICC cases, such HPV genotype distribution data are indispensable for predicting the impact of vaccination and HPV screening on prevention. Even with a successful vaccination program, vaccinated women will still require screening to detect those who will develop ICC from other High risk (HR) HPV genotypes not prevented by current vaccines. The aim of this review is to report on the prevalence of pHR/HR HPV types and multiple pHR/HR HPV genotypes in Kenya among HIV positive women with normal, abnormal cytology and ICC. Methods PUBMED, EMBASE, SCOPUS, and PROQUEST were searched for articles on HPV infection up to August 2nd 2016. Search terms were HIV, HPV, Cervical Cancer, Incidence or Prevalence, and Kenya. Results The 13 studies included yielded a total of 2116 HIV-infected women, of which 89 had ICC. The overall prevalence of pHR/HR HPV genotypes among HIV-infected women was 64% (95%CI: 50%-77%). There was a borderline significant difference in the prevalence of pHR/HR HPV genotypes between Female Sex workers (FSW) compared to non-FSW in women with both normal and abnormal cytology. Multiple pHR/HR HPV genotypes were highly prominent in both normal cytology/HSIL and ICC. The most prevalent HR HPV genotypes in women with abnormal cytology were HPV 16 with 26%, (95%CI: 23.0%-30.0%) followed by HPV 35 and 52, with 21% (95%CI: 18%-25%) and 18% (95%CI: 15%-21%), respectively. In women with ICC, the most prevalent HPV genotypes were HPV 16 (37%; 95%CI: 28%-47%) and HPV 18 (24%; 95%CI: 16%-33%). Conclusion HPV 16/18 gains prominence as the severity of cervical disease increases, with HPV 16/18 accounting for 61% (95%CI: 50.0%-70.0%) of all ICC cases. A secondary prevention program will be necessary as this population harbors multiple pHR/HR HPV co-infections, which may not be covered by current vaccines. A triage based on FSW as an indicator may be warranted. PMID:27764092

Human Papillomavirus (HPV) Vaccine

MedlinePlus

Why get vaccinated?HPV vaccine prevents infection with human papillomavirus (HPV) types that are associated with cause ... at http://www.cdc.gov/hpv. HPV Vaccine (Human Papillomavirus) Information Statement. U.S. Department of Health and ...

HPV Vaccine

MedlinePlus

... Safe Videos for Educators Search English Español HPV Vaccine KidsHealth / For Teens / HPV Vaccine What's in this ... starting at age 9. How Does the HPV Vaccine Work? The HPV vaccine is approved for people ...

Epidemiology of HPV genotypes in Uganda and the role of the current preventive vaccines: A systematic review

PubMed Central

2011-01-01

Background Limited data are available on the distribution of human papillomavirus (HPV) genotypes in the general population and in invasive cervical cancer (ICC) in Uganda. Yet, with the advent of preventive HPV vaccines that target HPV 16 and 18 responsible for causing about 70% of ICC cases in the world, such information is crucial to predict how vaccination and HPV-based screening will influence prevention of ICC. Methods To review the distribution of HPV infection and prevalent genotypes, electronic databases (e.g. PubMed/MEDLINE and HINARI) were searched for peer reviewed English articles on HPV infection up to November 30, 2010. Eligible studies were selected according to the following criteria: DNA-confirmed cervical or male genital HPV prevalence and genotypes, HPV incidence estimates and HPV seroprevalence among participants. Results Twenty studies were included in the review. Among HIV negative adult women, the prevalence of HR-HPV infections ranged from 10.2% -40.0% compared to 37.0% -100.0% among HIV positive women. Among HIV positive young women aged below 25 years, the prevalence of HR-HPV genotypes ranged from 41.6% -75.0% compared to 23.7% -67.1% among HIV negative women. Multiple infections with non vaccine HR-HPV genotypes were frequent in both HIV positive and HIV negative women. The main risk factors for prevalent HPV infections were age, lifetime number of sexual partners and HIV infection. Incident infections with HR-HPV genotypes were more frequent among adult HIV positive than HIV negative women estimated at 17.3 and 7.0 per 100 person-years, respectively. Similarly, incident HR-HPV among young women aged below 25 years were more frequent among HIV positive (40.0 per 100 person-years) than HIV negative women (20.3 per 100 person-years) women. The main risk factor for incident infection was HIV infection. HPV 16 and 18 were the most common genotypes in ICC with HPV 16/18 contributing up to 73.5% of cases with single infections. Among uncircumcised adult HIV positive males, HR-HPV prevalence ranged from 55.3% -76.6% compared to 38.6% -47.6% in HIV negative males. Incident and multiple HR-HPV infections were frequent in HIV positive males. Being uncircumcised was the main risk factor for both prevalent and incident HPV infection. Conclusion Infections with HR-HPV genotypes were very common particularly among HIV positive individuals and young women irrespective of HIV status. Given the high prevalence of HIV infection, HPV-associated conditions represent a major public health burden in Uganda. However, although the most common HPV genotypes in ICC cases in Uganda were those targeted by current preventive vaccines, there were a large number of individuals infected with other HR-HPV genotypes. Technology allowing, these other HR-HPV types should be considered in the development of the next generation of vaccines. PMID:21749691

Down-regulation of Toll-like Receptor TLR4 Is Associated with HPV DNA Integration in Penile Carcinoma.

PubMed

Damasdi, Miklos; Kovacs, Krisztina; Farkas, Nelli; Jakab, Ferenc; Kovacs, Gyula

2017-10-01

Development of penile cancers is attributed to HPV-related carcinogenesis. Our aim was to analyze HPV positivity and TLR4, p16 ink4a and p53 expression. HPV presence was assessed with virus-specific TaqMan PCR and HPV Genotyping Test in 31 penile cancers. Immunohistochemistry was carried out on tissue microarray. TLR4 expression was detected in 4 of the 16 HPV positive and 13 of the 15 HPV negative tumors. We found a significant inverse correlation between HPV positivity and TLR4 expression (p=0.0006). Ten of the 16 HPV-positive but none of the 15 HPV-negative tumors expressed p16INK4a. A significant correlation was seen between p53 expression and lack of HPV DNA (p=0.0191) as well as between TLR4 and p53 expression (p=0.0198) in penile cancers. Our findings suggest a protective role of TLR4 expression against HPV DNA integration and the viral and non-viral carcinogenesis of penile cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

HPV-QUEST: A highly customized system for automated HPV sequence analysis capable of processing Next Generation sequencing data set.

PubMed

Yin, Li; Yao, Jiqiang; Gardner, Brent P; Chang, Kaifen; Yu, Fahong; Goodenow, Maureen M

2012-01-01

Next Generation sequencing (NGS) applied to human papilloma viruses (HPV) can provide sensitive methods to investigate the molecular epidemiology of multiple type HPV infection. Currently a genotyping system with a comprehensive collection of updated HPV reference sequences and a capacity to handle NGS data sets is lacking. HPV-QUEST was developed as an automated and rapid HPV genotyping system. The web-based HPV-QUEST subtyping algorithm was developed using HTML, PHP, Perl scripting language, and MYSQL as the database backend. HPV-QUEST includes a database of annotated HPV reference sequences with updated nomenclature covering 5 genuses, 14 species and 150 mucosal and cutaneous types to genotype blasted query sequences. HPV-QUEST processes up to 10 megabases of sequences within 1 to 2 minutes. Results are reported in html, text and excel formats and display e-value, blast score, and local and coverage identities; provide genus, species, type, infection site and risk for the best matched reference HPV sequence; and produce results ready for additional analyses.

Human papilloma virus in oral cancer.

PubMed

Kim, Soung Min

2016-12-01

Cervical cancer is the second most prevalent cancer among women, and it arises from cells that originate in the cervix uteri. Among several causes of cervical malignancies, infection with some types of human papilloma virus (HPV) is well known to be the greatest cervical cancer risk factor. Over 150 subtypes of HPV have been identified; more than 40 types of HPVs are typically transmitted through sexual contact and infect the anogenital region and oral cavity. The recently introduced vaccine for HPV infection is effective against certain subtypes of HPV that are associated with cervical cancer, genital warts, and some less common cancers, including oropharyngeal cancer. Two HPV vaccines, quadrivalent and bivalent types that use virus-like particles (VLPs), are currently used in the medical commercial market. While the value of HPV vaccination for oral cancer prevention is still controversial, some evidence supports the possibility that HPV vaccination may be effective in reducing the incidence of oral cancer. This paper reviews HPV-related pathogenesis in cancer, covering HPV structure and classification, trends in worldwide applications of HPV vaccines, effectiveness and complications of HPV vaccination, and the relationship of HPV with oral cancer prevalence.

Detection and analysis of human papillomavirus 16 and 18 homologous DNA sequences in oral lesions.

PubMed

Wen, S; Tsuji, T; Li, X; Mizugaki, Y; Hayatsu, Y; Shinozaki, F

1997-01-01

The prevalence of human papillomavirus (HPV) 16 and 18 was investigated in oral lesions of the population of northeast China including squamous cell carcinomas (SCCs), candida leukoplakias, lichen planuses and papillomas, by southern blot hybridization with polymerase chain reaction (PCR). Amplified HPV16 and 18 E6 DNA was analyzed by cycle sequence. HPV DNA was detected in 14 of 45 SCCs (31.1%). HPV18 E6 DNA and HPV16 E6. DNA were detected in 24.4% and 20.0% of SCCs. respectively. Dual infection of both HPV 16 and HPV 18 was detected in 6 of 45 SCCs (13.3%), but not in other oral lesions. HPV 18 E6 DNA was also detected in 2 of 3 oral candida leukoplakias, but in none of the 5 papillomas. Our study indicated that HPV 18 infection might be more frequent than HPV 16 infection in oral SCCs in northeast Chinese, dual infection of high risk HPV types was restricted in oral SCCs, and that HPV infection might be involved in the pathogenesis of oral candida leukoplakia.

Impact localization on composite structures using time difference and MUSIC approach

NASA Astrophysics Data System (ADS)

Zhong, Yongteng; Xiang, Jiawei

2017-05-01

1-D uniform linear array (ULA) has the shortcoming of the half-plane mirror effect, which does not allow discriminating between a target placed above the array and a target placed below the array. This paper presents time difference (TD) and multiple signal classification (MUSIC) based omni-directional impact localization on a large stiffened composite structure using improved linear array, which is able to perform omni-directional 360° localization. This array contains 2M+3 PZT sensors, where 2M+1 PZT sensors are arranged as a uniform linear array, and the other two PZT sensors are placed above and below the array. Firstly, the arrival times of impact signals observed by the other two sensors are determined using the wavelet transform. Compared with each other, the direction range of impact source can be decided in general, 0°to 180° or 180°to 360°. And then, two dimensional multiple signal classification (2D-MUSIC) based spatial spectrum formula using the uniform linear array is applied for impact localization by the general direction range. When the arrival times of impact signals observed by upper PZT is equal to that of lower PZT, the direction can be located in x axis (0°or 180°). And time difference based MUSIC method is present to locate impact position. To verify the proposed approach, the proposed approach is applied to a composite structure. The localization results are in good agreement with the actual impact occurring positions.

Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial.

PubMed

Wheeler, Cosette M; Castellsagué, Xavier; Garland, Suzanne M; Szarewski, Anne; Paavonen, Jorma; Naud, Paulo; Salmerón, Jorge; Chow, Song-Nan; Apter, Dan; Kitchener, Henry; Teixeira, Júlio C; Skinner, S Rachel; Jaisamrarn, Unnop; Limson, Genara; Romanowski, Barbara; Aoki, Fred Y; Schwarz, Tino F; Poppe, Willy A J; Bosch, F Xavier; Harper, Diane M; Huh, Warner; Hardt, Karin; Zahaf, Toufik; Descamps, Dominique; Struyf, Frank; Dubin, Gary; Lehtinen, Matti

2012-01-01

We evaluated the efficacy of the human papillomavirus HPV-16/18 AS04-adjuvanted vaccine against non-vaccine oncogenic HPV types in the end-of-study analysis after 4 years of follow-up in PATRICIA (PApilloma TRIal against Cancer In young Adults). Healthy women aged 15-25 years with no more than six lifetime sexual partners were included in PATRICIA irrespective of their baseline HPV DNA status, HPV-16 or HPV-18 serostatus, or cytology. Women were randomly assigned (1:1) to HPV-16/18 vaccine or a control hepatitis A vaccine, via an internet-based central randomisation system using a minimisation algorithm to account for age ranges and study sites. The study was double-blind. The primary endpoint of PATRICIA has been reported previously; the present analysis evaluates cross-protective vaccine efficacy against non-vaccine oncogenic HPV types in the end-of-study analysis. Analyses were done for three cohorts: the according-to-protocol cohort for efficacy (ATP-E; vaccine n=8067, control n=8047), total vaccinated HPV-naive cohort (TVC-naive; no evidence of infection with 14 oncogenic HPV types at baseline, approximating young adolescents before sexual debut; vaccine n=5824, control n=5820), and the total vaccinated cohort (TVC; all women who received at least one vaccine dose, approximating catch-up populations that include sexually active women; vaccine n=9319, control=9325). Vaccine efficacy was evaluated against 6-month persistent infection, cervical intraepithelial neoplasia grade 2 or greater (CIN2+) associated with 12 non-vaccine HPV types (individually or as composite endpoints), and CIN3+ associated with the composite of 12 non-vaccine HPV types. This study is registered with ClinicalTrials.gov, number NCT00122681. Consistent vaccine efficacy against persistent infection and CIN2+ (with or without HPV-16/18 co-infection) was seen across cohorts for HPV-33, HPV-31, HPV-45, and HPV-51. In the most conservative analysis of vaccine efficacy against CIN2+, where all cases co-infected with HPV-16/18 were removed, vaccine efficacy was noted for HPV-33 in all cohorts, and for HPV-31 in the ATP-E and TVC-naive. Vaccine efficacy against CIN2+ associated with the composite of 12 non-vaccine HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68), with or without HPV-16/18 co-infection, was 46·8% (95% CI 30·7-59·4) in the ATP-E, 56·2% (37·2-69·9) in the TVC-naive, and 34·2% (20·4-45·8) in the TVC. Corresponding values for CIN3+ were 73·8% (48·3-87·9), 91·4% (65·0-99·0), and 47·5% (22·8-64·8). Data from the end-of-study analysis of PATRICIA show cross-protective efficacy of the HPV-16/18 vaccine against four oncogenic non-vaccine HPV types-HPV-33, HPV-31, HPV-45, and HPV-51-in different trial cohorts representing diverse groups of women. GlaxoSmithKline Biologicals. Copyright © 2012 Elsevier Ltd. All rights reserved.

HPV DNA test

MedlinePlus

... HPV testing in women; Cervical cancer - HPV DNA test; Cancer of cervix - HPV DNA test ... The HPV DNA test may be done during a Pap smear . You lie on a table and place your feet in stirrups. The ...

Human papillomavirus prevalence and type distribution in penile carcinoma.

PubMed

Miralles-Guri, C; Bruni, L; Cubilla, A L; Castellsagué, X; Bosch, F X; de Sanjosé, S

2009-10-01

Penile carcinoma is an uncommon and potentially mutilating disease with a heterogeneous aetiology. Several risk factors have been established for its development. Human papillomavirus (HPV) infection seems to play an important role in the development of a subset of these carcinomas and its presence is thought to be related to the histological type. HPV prevalence in penile tumours is reported to be associated to a variety of morphological changes. Its determination will provide a better estimate for HPV related cancer burden and its preventable fraction. A systematic and comprehensive literature review of the major penile cancer studies published from 1986 until June 2008 evaluating the HPV prevalence among the different histological types was carried out. 31 studies including 1466 penile carcinomas were reviewed. Global HPV prevalence was 46.9%. Relative contribution was: HPV-16 (60.23%), HPV-18 (13.35%), HPV-6/11 (8.13%), HPV-31 (1.16%), HPV-45 (1.16%), HPV-33 (0.97%), HPV-52 (0.58%), other types (2.47%). Assessment of multiple infections contribution is limited due to study design. Basaloid and warty squamous cell carcinomas were the most frequent HPV-related histological types, but keratinising and non-keratinising subtypes also showed prevalence rates of around 50%. About half of the penile tumours were associated with HPV 16-18 with little presence of other genotypes. Research on the mechanisms behind penile carcinogenesis is warranted. Available HPV vaccines are likely to be effective in penile tumours.

The prevalence of human papillomavirus genotypes in penile cancers from northern Thailand.

PubMed

Senba, Masachika; Kumatori, Atsushi; Fujita, Shuichi; Jutavijittum, Prapan; Yousukh, Amnat; Moriuchi, Toshiyuki; Nakamura, Tsuyoshi; Toriyama, Kan

2006-10-01

The highest frequency of penile cancer occurs in Asia, Africa, and Latin America, and there have been a few reports concerning the association of penile cancer with human papillomavirus (HPV) infection in these areas. The objective of this study was to determine the relation between penile cancer and the prevalence of HPV genotypes in northern Thailand. Eighty-eight specimens of penile tissue (65 malignant, 1 pre-malignant, and 22 benign cases) were examined to determine the association of HPV infection. An in situ hybridization (ISH) method was used to detect and localize HPV-DNA. Sensitive HPV polymerase chain reaction (PCR) procedure was used for detection of HPV-DNA, and DNA sequencing was used to identify the HPV genotype. HPV-DNA was detected in 53.8% and 81.5% of cases of penile cancer, using ISH and PCR, respectively. The high-risk HPV-16, most commonly associated with penile cancer in previous reports, was found in only one case in this study. The most prevalent genotype was the high-risk HPV-18, found in 55.4% of the cases (32.3% single and 23.1% multiple infection) followed by the low-risk HPV-6, found in 43.1% of the cases (24.6% single and 18.5% multiple infection). In this study, penile cancer was found to be highly correlated with HPV-DNA. Specifically, infection with both the low-risk HPV-6 and the high-risk HPV-18 is the characteristic prevalence of HPV genotypes in penile cancer in this area.

The role of miRNAs in human papilloma virus (HPV)-associated cancers: bridging between HPV-related head and neck cancer and cervical cancer

PubMed Central

Lajer, C B; Garnæs, E; Friis-Hansen, L; Norrild, B; Therkildsen, M H; Glud, M; Rossing, M; Lajer, H; Svane, D; Skotte, L; Specht, L; Buchwald, C; Nielsen, F C

2012-01-01

Background: Although the role of human papilloma virus (HPV) in cervical squamous cell carcinoma (CSCC) is well established, the role in head and neck SCC (HNSCC) is less clear. MicroRNAs (miRNAs) have a role in the cancer development, and HPV status may affect the miRNA expression pattern in HNSCC. To explore the influence of HPV in HNSCC, we made a comparative miRNA profile of HPV-positive (HPV+) and HPV-negative (HPV−) HNSCC against CSCC. Methods: Fresh frozen and laser microdissected-paraffin-embedded samples obtained from patients with HPV+/HPV− HNSCC, CSCC and controls were used for microarray analysis. Differentially expressed miRNAs in the HPV+ and HPV− HNSCC samples were compared with the differentially expressed miRNAs in the CSCC samples. Results: Human papilloma virus positive (+) HNSCC had a distinct miRNA profile compared with HPV− HNSCC. Significantly more similarity was seen between HPV+ HNSCC and CSCC than HPV− and CSCC. A set of HPV core miRNAs were identified. Of these especially the miR-15a/miR-16/miR195/miR-497 family, miR-143/miR-145 and the miR-106-363 cluster appear to be important within the known HPV pathogenesis. Conclusion: This study adds new knowledge to the known pathogenic pathways of HPV and substantiates the oncogenic role of HPV in subsets of HNSCCs. PMID:22472886

Moderate Awareness and Limited Knowledge Relating to Cervical Cancer, HPV, and the HPV Vaccine Among Hispanics/Latinos in Utah.

PubMed

Bodson, Julia; Warner, Echo L; Kepka, Deanna

2016-07-01

We investigate the demographic factors associated with human papillomavirus (HPV) vaccine-related awareness and knowledge in an emerging (rather than established) Hispanic/Latino population. We surveyed 119 Spanish-speaking, mostly low-income and immigrant, Hispanic/Latino parents and guardians of adolescents 11 to 17 years old (i.e., eligible to receive the HPV vaccine) about their HPV vaccine-related awareness and knowledge. Data collection took place between August 2013 and October 2013 in Salt Lake City, Utah. Participants had moderately high awareness scores, with more than half the participants reporting having heard of cervical cancer (84.5%), HPV (76.4%), and the HPV vaccine (67.3%). HPV vaccine-related knowledge was low, with fewer than half the participants reporting they knew that most people are infected with HPV (32.7%), that HPV is asymptomatic among women (16.4%), that the HPV vaccine requires more than one dose (33.6%), and that the HPV vaccine is recommended for adolescent girls (47.3%) and boys (35.5%). Combined awareness and knowledge was significantly associated with educational attainment (p = .02) and country of origin (p = .03). Results demonstrate moderate to high HPV vaccine-related awareness and limited HPV vaccine-related knowledge among Hispanic/Latino parents living in Utah. These findings will inform educational interventions to improve the HPV vaccine-related awareness and knowledge in this vulnerable population. © 2016 Society for Public Health Education.

Human papillomavirus infection and the malignant transformation of sinonasal inverted papilloma: A meta-analysis.

PubMed

Zhao, Ren-Wu; Guo, Zhi-Qiang; Zhang, Ru-Xin

2016-06-01

A growing number of molecular epidemiological studies have been conducted to evaluate the association between human papillomavirus (HPV) infection and the malignancy of sinonasal inverted papilloma (SNIP). However, the results remain inconclusive. Here, a meta-analysis was conducted to quantitatively assess this association. Case-control studies investigating SNIP tissues for presence of HPV DNA were identified. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the Mantel-Haenszel method. An assessment of publication bias and sensitivity analysis were also performed. We calculated a pooled OR of 2.16 (95% CI=1.46-3.21, P<0.001) without statistically significant heterogeneity or publication bias. Stratification by HPV type showed a stronger association for patients with high-risk HPV (hrHPV) types, HPV-16, HPV-18, and HPV-16/18 infection (OR=8.8 [95% CI: 4.73-16.38], 8.04 [95% CI: 3.34-19.39], 18.57 [95% CI: 4.56-75.70], and 26.24 [4.35-158.47], respectively). When only using PCR studies, pooled ORs for patients with hrHPV, HPV-16, and HPV18 infection still reached statistical significance. However, Egger's test reflected significant publication bias in the HPV-16 sub-analysis (P=0.06), and the adjusted OR was no longer statistically significant (OR=1.65, 95%CI: 0.58-4.63). These results suggest that HPV infection, especially hrHPV (HPV-18), is significantly associated with malignant SNIP. Copyright © 2016 Elsevier B.V. All rights reserved.

Human Papilloma Virus Genotype Distribution in Cervical lesions in Zanjan, Iran

PubMed

Ahmadi, Shahrzad; Goudarzi, Hossein; Jalilvand, Ahmad; Esmaeilzadeh, Abdolreza

2017-12-29

Objective: Cervical cancer is one of the most common cancers among women all over the world, and main cause is persistent infection with high risk human papillomavirus (HPV) strains. It has been reported that the distribution and prevalence of HPV types varies by geographical region, so that this is important for prevention by type-specific vaccines. The aim of current study was to determine the genotype distribution of HPV using the INNO-LiPA genotyping assay in Zanjan province, North West Iran. Methods: A total of 112 formalin-fixed paraffin embedded (FFPE) tissue samples from cases of low-grade intraepithelial lesion (LSIL), high-grade intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC) were collected. The polymerase chain reaction (PCR) was used to amplify DNA for genotyping. Results: Among the 112 samples from females (ranging from 20 to 69 years, mean age 43.8 ± 10.1) tested for HPV DNA, 50 samples were positive. Based on results of genotyping, most common HPV genotypes were HPV18 (48%) followed by HPV-6 (24%), HPV73 (16%), HPV-51(8%), HPV-31(8%), HPV-16 (8%), HPV-56 (4%), HPV-44 (4%). Conclusion: While HPV infection is the major etiological factor for cervical cancer, presence was relatively low in our survey. In the positive cases, however, HPV18 was the most common in line with many other populations. The fact that types vary among different populations must clearly be taken into account in design of vaccines for our country. Creative Commons Attribution License

Modified general primer PCR system for sensitive detection of multiple types of oncogenic human papillomavirus.

PubMed

Söderlund-Strand, Anna; Carlson, Joyce; Dillner, Joakim

2009-03-01

Human papillomavirus (HPV) infection is a necessary cause of cervical cancer and cervical dysplasia. Accurate and sensitive genotyping of multiple oncogenic HPVs is essential for a multitude of both clinical and research uses. We developed a modified general primer (MGP) PCR system with five forward and five reverse consensus primers. The MGP system was compared to the classical HPV general primer system GP5+/6+ using a proficiency panel with HPV plasmid dilutions as well as cervical samples from 592 women with low-grade cytological abnormalities. The reference method (GP5+/6+) had the desirable high sensitivity (five copies/PCR) for five oncogenic HPV types (HPV type 16 [HPV-16], HPV-18, HPV-56, HPV-59, and HPV-66). The MGP system was able to detect all 14 oncogenic HPV types at five copies/PCR. In the clinical samples, the MGP system detected a significantly higher proportion of women with more than two concomitant HPV infections than did the GP5+/6+ system (102/592 women compared to 42/592 women). MGP detected a significantly greater number of infections with HPV-16, -18, -31, -33, -35, -39, -42, -43, -45, -51, -52, -56, -58, and -70 than did GP5+/6+. In summary, the MGP system primers allow a more sensitive amplification of most of the HPV types that are established as oncogenic and had an improved ability to detect multiple concomitant HPV infections.

Human papillomavirus-mediated carcinogenesis and HPV-associated oral and oropharyngeal squamous cell carcinoma. Part 2: Human papillomavirus associated oral and oropharyngeal squamous cell carcinoma

PubMed Central

2010-01-01

Human papillomavirus (HPV) infection of the mouth and oropharynx can be acquired by a variety of sexual and social forms of transmission. HPV-16 genotype is present in many oral and oropharyngeal squamous cell carcinomata. It has an essential aetiologic role in the development of oropharyngeal squamous cell carcinoma in a subset of subjects who are typically younger, are more engaged with high-risk sexual behaviour, have higher HPV-16 serum antibody titer, use less tobacco and have better survival rates than in subjects with HPV-cytonegative oropharyngeal squamous cell carcinoma. In this subset of subjects the HPV-cytopositive carcinomatous cells have a distinct molecular profile. In contrast to HPV-cytopositive oropharyngeal squamous cell carcinoma, the causal association between HPV-16 and other high-risk HPV genotypes and squamous cell carcinoma of the oral mucosa is weak, and the nature of the association is unclear. It is likely that routine administration of HPV vaccination against high-risk HPV genotypes before the start of sexual activity will bring about a reduction in the incidence of HPV-mediated oral and oropharyngeal squamous cell carcinoma. This article focuses on aspects of HPV infection of the mouth and the oropharynx with emphasis on the link between HPV and squamous cell carcinoma, and on the limitations of the available diagnostic tests in identifying a cause-and-effect relationship of HPV with squamous cell carcinoma of the mouth and oropharynx. PMID:20633288

Awareness and Knowledge About HPV and HPV Vaccine Among Romanian Women.

PubMed

Grigore, Mihaela; Teleman, Sergiu Iuliu; Pristavu, Anda; Matei, Mioara

2018-02-01

Cervical cancer is one of the most prevalent gynecological malignancies worldwide. Romania has the highest incidence of this type of cancer in Europe. A successful prevention strategy has to consider the primary prevention measures (including health education on human papilloma virus (HPV) infection but also vaccination). The aim of this study was to assess the knowledge and attitudes of Romanian women about HPV and HPV vaccine. We conducted a cross-sectional study survey of 454 women using an anonymously completed questionnaire covering the awareness and knowledge of HPV infection and attitudes to vaccination. We also analyzed the discussions and conclusion from a focus group of healthcare professionals regarding (1) HPV and HPV awareness and attitude, and (2) suggestions for improving HPV vaccine knowledge and acceptance. 69.2% of women were aware about HPV but their knowledge was minimal and incomplete. While 62.3% had heard about HPV vaccine, only 50.7% had a positive attitude toward it. The main barriers to vaccination were the fear of side effects, the perception that is risky, and the financial concerns. Deficiencies in knowledge were noted for vaccine, genital warts, or risks factors for HPV infection like the early onset of sexual life. The information regarding HPV and vaccine is not always accurate and complete, and only 50.7% of women have a positive attitude toward the vaccine. More educational programs and clearer communication are needed to raise awareness and knowledge regarding HPV and HPV vaccine.

Sensitivity and specificity of oral HPV detection for HPV-positive head and neck cancer.

PubMed

Gipson, Brooke J; Robbins, Hilary A; Fakhry, Carole; D'Souza, Gypsyamber

2018-02-01

The incidence of HPV-related head and neck squamous cell carcinoma (HPV-HNSCC) is increasing. Oral samples are easy and non-invasive to collect, but the diagnostic accuracy of oral HPV detection methods for classifying HPV-positive HNSCC tumors has not been well explored. In a systematic review, we identified eight studies of HNSCC patients meeting our eligibility criteria of having: (1) HPV detection in oral rinse or oral swab samples, (2) tumor HPV or p16 testing, (3) a publication date within the last 10 years (January 2007-May 2017, as laboratory methods change), and (4) at least 15 HNSCC cases. Data were abstracted from each study and a meta-analysis performed to calculate sensitivity and specificity. Eight articles meeting inclusion criteria were identified. Among people diagnosed with HNSCC, oral HPV detection has good specificity (92%, 95% CI = 82-97%) and moderate sensitivity (72%, 95% CI = 45-89%) for HPV-positive HNSCC tumor. Results were similar when restricted to studies with only oropharyngeal cancer cases, with oral rinse samples, or testing for HPV16 DNA (instead of any oncogenic HPV) in the oral samples. Among those who already have HNSCC, oral HPV detection has few false-positives but may miss one-half to one-quarter of HPV-related cases (false-negatives). Given these findings in cancer patients, the utility of oral rinses and swabs as screening tests for HPV-HNSCC among healthy populations is probably limited. Copyright © 2017 Elsevier Ltd. All rights reserved.

Linear CCD attitude measurement system based on the identification of the auxiliary array CCD

NASA Astrophysics Data System (ADS)

Hu, Yinghui; Yuan, Feng; Li, Kai; Wang, Yan

2015-10-01

Object to the high precision flying target attitude measurement issues of a large space and large field of view, comparing existing measurement methods, the idea is proposed of using two array CCD to assist in identifying the three linear CCD with multi-cooperative target attitude measurement system, and to address the existing nonlinear system errors and calibration parameters and more problems with nine linear CCD spectroscopic test system of too complicated constraints among camera position caused by excessive. The mathematical model of binocular vision and three linear CCD test system are established, co-spot composition triangle utilize three red LED position light, three points' coordinates are given in advance by Cooperate Measuring Machine, the red LED in the composition of the three sides of a triangle adds three blue LED light points as an auxiliary, so that array CCD is easier to identify three red LED light points, and linear CCD camera is installed of a red filter to filter out the blue LED light points while reducing stray light. Using array CCD to measure the spot, identifying and calculating the spatial coordinates solutions of red LED light points, while utilizing linear CCD to measure three red LED spot for solving linear CCD test system, which can be drawn from 27 solution. Measured with array CCD coordinates auxiliary linear CCD has achieved spot identification, and has solved the difficult problems of multi-objective linear CCD identification. Unique combination of linear CCD imaging features, linear CCD special cylindrical lens system is developed using telecentric optical design, the energy center of the spot position in the depth range of convergence in the direction is perpendicular to the optical axis of the small changes ensuring highprecision image quality, and the entire test system improves spatial object attitude measurement speed and precision.

Thermal-Independent Properties of PIN-PMN-PT Single-Crystal Linear-Array Ultrasonic Transducers

PubMed Central

Chen, Ruimin; Wu, Jinchuan; Lam, Kwok Ho; Yao, Liheng; Zhou, Qifa; Tian, Jian; Han, Pengdi; Shung, K. Kirk

2013-01-01

In this paper, low-frequency 32-element linear-array ultrasonic transducers were designed and fabricated using both ternary Pb(In1/2Nb1/2)–Pb(Mg1/3Nb2/3)–PbTiO3 (PIN-PMN-PT) and binary Pb(Mg1/3Nb2/3)–PbTiO3 (PMN-PT) single crystals. Performance of the array transducers was characterized as a function of temperature ranging from room temperature to 160°C. It was found that the array transducers fabricated using the PIN-PMN-PT single crystal were capable of satisfactory performance at 160°C, having a −6-dB bandwidth of 66% and an insertion loss of 37 dB. The results suggest that the potential of PIN-PMN-PT linear-array ultrasonic transducers for high-temperature ultrasonic transducer applications is promising. PMID:23221227

HPV-relatedness definitions for classifying HPV-related oropharyngeal cancer patient do impact on TNM classification and patients' survival.

PubMed

Taberna, Miren; Mena, Marisa; Tous, Sara; Pavón, Miquel Angel; Oliva, Marc; León, Xavier; Garcia, Jacinto; Guix, Marta; Hijano, Rafael; Bonfill, Teresa; Aguilà, Antón; Alemany, Laia; Mesía, Ricard

2018-01-01

Given the different nature and better outcomes of oropharyngeal carcinoma (OPC) associated with human papillomavirus (HPV) infection, a novel clinical stage classification for HPV-related OPC has been accepted for the 8th edition AJCC TNM (ICON-S model). However, it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value. The aim of this study was to compare different staging system models proposed for HPV-related OPC patients: 7th edition AJCC TNM, RPA stage with non-anatomic factors (Princess Margaret), RPA with N categories for nasopharyngeal cancer (MD-Anderson) and AHR-new (ICON-S), according to different HPV-relatedness definitions: HPV-DNA detection plus an additional positive marker (p16INK4a or HPV-mRNA), p16INK4a positivity alone or the combination of HPV-DNA/p16INK4a positivity as diagnostic tests. A total of 788 consecutive OPC cases diagnosed from 1991 to 2013 were considered eligible for the analysis. Of these samples, 66 (8.4%) were positive for HPV-DNA and (p16INK4a or HPV-mRNA), 83 (10.5%) were p16INK4a positive and 58 (7.4%) were double positive for HPV-DNA/p16INK4a. ICON-S model was the staging system, which performed better in our series when using at least two biomarkers to define HPV-causality. When the same analysis was performed considering only p16INK4a-positivity, RPA stage with non-anatomic factors (Princess Margaret) has the best classification based on AIC criteria. HPV-relatedness definition for classifying HPV-related OPC patient do impact on TNM classification and patients' survival. Further studies assessing HPV-relatedness definitions are warranted to better classify HPV-related OPC patients in the era of de-escalation clinical trials.

Clinical Study of Styping Detection of Human Papillomavirus (HPV) Infection with Microarray from Paraffinembedded Specimens of Cervical Cancer and Precursor Lesions.

PubMed

Li, Hai; Wang, Xubo; Geng, Jianxiang; Zhao, Xue

2015-09-01

The prevalence and type distribution of human papillomavirus (HPV) in cervical cancer and cervical intraepithelial neoplasia (CIN) in Jiangsu, China was investigated. A total of 93 cases with cervical cancer and 176 CINII-III tissue samples were obtained from women undergoing biopsy or surgery. The 1047 exfoliated cervical cell samples were collected with cervical brush in physical examination women. HPV DNA and typing were examined by polymerase chain reaction (PCR) and gene-chip. The results showed that HPV DNA was detected in 82 cases with cervical cancer (88.17%), HPV 16 being detected in 65 (69.89%) cases, HPV 18 in 12 (12.90%) cases, HPV 33 in 10 (10.75%) cases, HPV 31 in 4 (4.30%) cases, and HPV 45 in 3 (3.23%) cases. HPV DNA was detected in 154 cases with CINII-III (87.50%), HPV 16 being detected in 92 (52.27%) cases, HPV 18 in 50 (28.41%) cases, HPV 33 in 25 (14.21%) cases, HPV 58 in 25 (14.21%) cases, and HPV 31 in 20 (11.36%) cases. About 20.43% cervical cancer and 38.64% CINII-III specimens exhibited multiple infections (p < 0.01). The total positive rate, single infection and mixed infection rate of the CINII-III and SCC group all had a significant difference (p < 0.05) when compared with the normal cells group. The total positive rate, single infection rate and mixed infection rate of CINII-III group did not show significant difference (p > 0.05) when compared with SCC group. CINII-III and SCC had all intimate relation with HPV infection. The high prevalence of HPV 16, 18, 33, 31 and 58 in Jiangsu (China) deserves more attention, as it has important implications for the successful use of HPV vaccine and choice of diagnostic methods.

Comparison of Human Papillomavirus Detection by Aptima HPV and cobas HPV Tests in a Population of Women Referred for Colposcopy following Detection of Atypical Squamous Cells of Undetermined Significance by Pap Cytology

PubMed Central

Castle, Philip E.; Eaton, Barbara; Reid, Jennifer; Dockter, Janel

2015-01-01

Few studies have compared the cobas HPV test to the Aptima HPV assay (AHPV) and the Aptima HPV 16 18/45 genotype assay (AHPV GT) for high-risk human papillomavirus (hrHPV) detection, clinical performance in detecting cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+) diagnoses, and risk stratification by partial HPV genotyping. The cobas HPV test is a DNA test that separately and concurrently detects HPV16, HPV18, and a pool of 12 other hrHPV types. AHPV is an RNA test for a pool of 14 hrHPV genotypes, and AHPV GT is an RNA test run on AHPV-positive results to detect HPV16 separately from HPV18 and HPV45, which are detected together. In a population of patients (n = 988) referred for colposcopy because of a cervical Pap cytology result of atypical squamous cells of undetermined significance (ASC-US), a cervical scrape specimen was taken, placed into a ThinPrep Pap test vial containing PreservCyt liquid cytology medium, and tested in a blinded fashion with cobas and AHPV and with AHPV GT for AHPV-positive results. The final diagnoses were based on a consensus panel review of the biopsy specimen histology. AHPV and cobas were equally sensitive for CIN2+ diagnoses (89.4% each; P = 1.000), and AHPV was more specific than cobas (63.1% versus 59.3%; P ≤ 0.001). The percent total agreement, percent positive agreement, and kappa value were 90.9%, 81.1%, and 0.815, respectively. Risk stratification using partial HPV genotyping was similar for the two assays. AHPV and AHPV GT had similar sensitivity and risk stratification to cobas HPV, but they were more specific than cobas HPV. PMID:25653409

Human papillomavirus genotypes in penile cancers from Japanese patients and HPV-induced NF-κB activation.

PubMed

Senba, Masachika; Mori, Naoki; Wada, Akihiro; Fujita, Shuichi; Yasunami, Michio; Irie, Sumiko; Hayashi, Tomayoshi; Igawa, Tsukasa; Kanetake, Hiroshi; Takahara, Osamu; Toriyama, Kan

2010-03-01

The causal relationship between chronic inflammation and cancer is widely accepted. Numerous investigations have identified nuclear factor-κB (NF-κB) as an important modulator in driving chronic inflammation to cancer. This study aimed to determine the prevalence of human papillomavirus (HPV) in penile cancer in Japanese patients and whether NF-κB is subsequently overexpressed in penile cancer. Thirty-four specimens of penile tissue (16 malignant and 18 benign cases) were examined to determine the association of HPV infection. An in situ hybridization (ISH) method was used to detect and localize HPV-DNA. A sensitive HPV polymerase chain reaction (PCR) procedure was used for the detection of HPV-DNA, and DNA sequencing was used to identify the HPV genotype. HPV-DNA was detected in 37.5 and 75% of cases of penile cancer, using ISH and PCR, respectively. Our efforts to detect HPV genotypes were unsuccessful as HPV-DNA could not be extracted from these materials. Using ISH, a prevalence of 68.2% of HPV infection was found in penile cancer in Kenyan patients in east Africa. In the present study, all 9 HPV-positive cases, (100%) were NF-κB-positive in the nucleus and/or cytoplasm. In contrast, of the 25 HPV-negative cases, 15 (60%) were NF-κB-positive in the nucleus and/or cytoplasm. Therefore, ISH is a method which is able to prove infection of a large quantity of HPV more effectively when compared with PCR. Thus, a large quantity of HPV infection leads to the activity of NF-κB. The most prevalent genotype was the HPV-22 found in 83.3% of the penile cancer cases. In addition, HPV-11 was found in 81.8% of the non-cancer cases. For cases with a high level of infection, the activity of NF-κB increased compared with those with a low level of HPV infection.

HPV-relatedness definitions for classifying HPV-related oropharyngeal cancer patient do impact on TNM classification and patients’ survival

PubMed Central

Mena, Marisa; Tous, Sara; Pavón, Miquel Angel; Oliva, Marc; León, Xavier; Garcia, Jacinto; Guix, Marta; Hijano, Rafael; Bonfill, Teresa; Aguilà, Antón; Alemany, Laia; Mesía, Ricard

2018-01-01

Background Given the different nature and better outcomes of oropharyngeal carcinoma (OPC) associated with human papillomavirus (HPV) infection, a novel clinical stage classification for HPV-related OPC has been accepted for the 8th edition AJCC TNM (ICON-S model). However, it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value. Material and methods The aim of this study was to compare different staging system models proposed for HPV-related OPC patients: 7th edition AJCC TNM, RPA stage with non-anatomic factors (Princess Margaret), RPA with N categories for nasopharyngeal cancer (MD-Anderson) and AHR-new (ICON-S), according to different HPV-relatedness definitions: HPV-DNA detection plus an additional positive marker (p16INK4a or HPV-mRNA), p16INK4a positivity alone or the combination of HPV-DNA/p16INK4a positivity as diagnostic tests. Results A total of 788 consecutive OPC cases diagnosed from 1991 to 2013 were considered eligible for the analysis. Of these samples, 66 (8.4%) were positive for HPV-DNA and (p16INK4a or HPV-mRNA), 83 (10.5%) were p16INK4a positive and 58 (7.4%) were double positive for HPV-DNA/p16INK4a. ICON-S model was the staging system, which performed better in our series when using at least two biomarkers to define HPV-causality. When the same analysis was performed considering only p16INK4a-positivity, RPA stage with non-anatomic factors (Princess Margaret) has the best classification based on AIC criteria. Conclusion HPV-relatedness definition for classifying HPV-related OPC patient do impact on TNM classification and patients’ survival. Further studies assessing HPV-relatedness definitions are warranted to better classify HPV-related OPC patients in the era of de-escalation clinical trials. PMID:29664911

Persistence of type-specific human papillomavirus infection and increased long-term risk of cervical cancer.

PubMed

Chen, Hui-Chi; Schiffman, Mark; Lin, Ching-Yu; Pan, Mei-Hung; You, San-Lin; Chuang, Li-Chung; Hsieh, Chang-Yao; Liaw, Kai-Li; Hsing, Ann W; Chen, Chien-Jen

2011-09-21

Human papillomavirus (HPV) persistence is the pivotal event in cervical carcinogenesis. We followed a large-scale community-based cohort for 16 years to investigate the role of genotype-specific HPV persistence in predicting cervical cancer including invasive and in situ carcinoma. At the baseline examination in 1991-1992, 11,923 participants (aged 30-65 years) consented to HPV testing and cytology; 6923 participants were reexamined in 1993-1995. For HPV testing, we used a polymerase chain reaction-based assay that detected 39 HPV types. Women who developed cervical cancer were identified from cancer and death registries. Cumulative risks for developing cervical cancer among infected and persistently infected women were calculated by the Kaplan-Meier method. Of 10,123 women who were initially cytologically normal, 68 developed cervical cancer. The 16-year cumulative risks of subsequent cervical cancer for women with HPV16, HPV58 (without HPV16), or other carcinogenic HPV types (without HPV16 or HPV58) were 13.5%, 10.3%, and 4.0%, respectively, compared with 0.26% for HPV-negative women. Women with type-specific persistence of any carcinogenic HPV had greatly increased risk compared with women who were HPV-negative at both visits (hazard ratio = 75.4, 95% confidence interval = 31.8 to 178.9). The cumulative cervical cancer risks following persistent carcinogenic HPV infections increased with age: The risks were 5.5%, 14.4%, and 18.1% for women aged 30-44 years, 45-54 years, and 55 years and older, respectively. However, newly acquired infections were associated with a low risk of cervical cancer regardless of age. HPV negativity was associated with a very low long-term risk of cervical cancer. Persistent detection of HPV among cytologically normal women greatly increased risk. Thus, it is useful to perform repeated HPV testing following an initial positive test.

Variants in human papillomavirus receptor and associated genes are associated with type-specific HPV infection and lesion progression of the cervix

PubMed Central

Chen, Tingting; Yang, Shizhou; Huang, Yongjie; Hong, Die; Li, Yang; Chen, Xiaojing; Wang, Xinyu; Cheng, Xiaodong; Lu, Weiguo; Xie, Xing

2016-01-01

Human papillomavirus (HPV) infects cervical epithelial cells through cellular membrane receptors, and then induces the initiation and progression of cervical cancer. Single nucleotide polymorphisms (SNPs) may impact the susceptibility and outcome of diseases, but it's still unknown whether variant in HPV receptor and associated genes is associated with type-specific HPV infection and cervical lesion progression. We examined 96 SNPs in 8 genes which may participate in the HPV infection process in 875 samples with HPV negative or single HPV16, 18, 52, 58 positive from 3299 cervical exfoliated cell samples, by Illumina BeadXpress VeraCode platform, and analyzed the correlation between the SNPs and type-specific HPV infection and cervical lesions progression. We found rs28384376 in EGFR and rs12034979 in HSPG2 significantly correlated to HPV16 infection; rs2575738, rs2575712, rs2575735 in SDC2 and rs6697265 in HSPG2 significantly correlated to HPV18 infection; rs10510097 in FGFR2, rs12718946 in EGFR significantly correlated to HPV52 infection; rs4947972 in EGFR, rs2981451 in FGFR2, rs2575735 in SDC2 significantly correlated to HPV58 infection. And rs3135772, rs1047057 and rs2556537 in FGFR2, rs12034979 in HSPG2, rs16894821 in SDC2 significantly correlated to cervical lesion progression induced by HPV16 infection; rs6697265 and rs6680566 in HSPG2, rs16860426 in ITGA6 by HPV18 infection; rs878949 in HSPG2, rs12718946 and rs12668175 in EGFR by HPV52 infection; no SNP by HPV58 infection. Our findings suggest that HPV receptor and associated gene variants may influence the susceptibilities to HPV type-specific infection and cervical lesion progression, which might have a potential application value in cervical cancer screening and therapy. PMID:27223085

Options in human papillomavirus (HPV) detection for cervical cancer screening: comparison between full genotyping and a rapid qualitative HPV-DNA assay in Ghana.

PubMed

Obiri-Yeboah, Dorcas; Adu-Sarkodie, Yaw; Djigma, Florencia; Akakpo, Kafui; Aniakwa-Bonsu, Ebenezer; Amoako-Sakyi, Daniel; Jacques, Simpore; Mayaud, Philippe

2017-01-01

Modern cervical cancer screening increasingly relies on the use of molecular techniques detecting high-risk oncogenic human papillomavirus (hr-HPV). A major challenge for developing countries like Ghana has been the unavailability and costs of HPV DNA-based testing. This study compares the performance of care HPV, a semi-rapid and affordable qualitative detection assay for 14 hr-HPV genotypes, with HPV genotyping, for the detection of cytological cervical squamous intraepithelial lesions (SIL). A study comparing between frequency matched HIV-1 seropositive and HIV-seronegative women was conducted in the Cape Coast Teaching Hospital, Ghana. A systematic sampling method was used to select women attending clinics in the hospital. Cervical samples were tested for HPV by care HPV and Anyplex-II HPV28 genotyping assay, and by conventional cytology. A total of 175 paired results (94 from HIV-1 seropositive and 81 from HIV-seronegative women) were analyzed based on the ability of both tests to detect the 14 hr-HPV types included in the care HPV assay. The inter-assay concordance was 94.3% (95%CI: 89.7-97.2%, kappa = 0.88), similar by HIV serostatus. The care HPV assay was equally sensitive among HIV-1 seropositive and seronegative women (97.3% vs. 95.7%, p  = 0.50) and slightly more specific among HIV-seronegative women (85.0% vs. 93.1%, p  = 0.10). care HPV had good sensitivity (87.5%) but low specificity (52.1%) for the detection of low SIL or greater lesions, but its performance was superior to genotyping (87.5 and 38.8%, respectively). Reproducibility of care HPV, tested on 97 samples by the same individual was 82.5% (95%CI: 73.4-89.4%). The performance characteristics of care HPV compared to genotyping suggest that this simpler and cheaper HPV detection assay could offer a suitable alternative for HPV screening in Ghana.

A randomized controlled trial of Human Papillomavirus (HPV) testing for cervical cancer screening: trial design and preliminary results (HPV FOCAL Trial)

PubMed Central

2010-01-01

Background In the HPV FOCAL trial, we will establish the efficacy of hr-HPV DNA testing as a stand-alone screening test followed by liquid based cytology (LBC) triage of hr-HPV-positive women compared to LBC followed by hr-HPV triage with ≥ CIN3 as the outcome. Methods/Design HPV-FOCAL is a randomized, controlled, three-armed study over a four year period conducted in British Columbia. It will recruit 33,000 women aged 25-65 through the province's population based cervical cancer screening program. Control arm: LBC at entry and two years, and combined LBC and hr-HPV at four years among those with initial negative results and hr-HPV triage of ASCUS cases; Two Year Safety Check arm: hr-HPV at entry and LBC at two years in those with initial negative results with LBC triage of hr-HPV positives; Four Year Intervention Arm: hr-HPV at entry and combined hr-HPV and LBC at four years among those with initial negative results with LBC triage of hr-HPV positive cases Discussion To date, 6150 participants have a completed sample and epidemiologic questionnaire. Of the 2019 women enrolled in the control arm, 1908 (94.5%) were cytology negative. Women aged 25-29 had the highest rates of HSIL (1.4%). In the safety arm 92.2% of women were hr-HPV negative, with the highest rate of hr-HPV positivity found in 25-29 year old women (23.5%). Similar results were obtained in the intervention arm HPV FOCAL is the first randomized trial in North America to examine hr-HPV testing as the primary screen for cervical cancer within a population-based cervical cancer screening program. Trial Registration International Standard Randomised Controlled Trial Number Register, ISRCTN79347302 PMID:20334685

Acceptability of HPV vaccines and associations with perceptions related to HPV and HPV vaccines among male baccalaureate students in Hong Kong

PubMed Central

2018-01-01

Objectives The highly infectious human papillomavirus (HPV) causes both genital warts and cervical cancer in women. In 2009, the prevalence of genital warts in Hong Kong was 203.7 per 100,000 person-years. Cervical cancer, more seriously, was the eight most common cancer among women and girls in Hong Kong, accounting for 2.3% of all new cancer cases in females in 2014. Cervical cancer is a significant global public health problem and HPV is a major risk factor leading to the development of cervical cancer. HPV is also the most common sexually transmitted disease among university students. This is the first study to examine the acceptability of HPV vaccines and associations with perceptions related to HPV and HPV vaccines among the male baccalaureate student population locally. Methods A self-administrative cross-sectional survey was used to assess whether male baccalaureate students from eight local Hong Kong universities intended to be immunized for HPV. The study also asked questions concerning how its subjects perceived HPV and HPV vaccines using the Health Belief Model. Data collection spanned from June to September 2015. A multiple stepwise regression model was used to examine associations between cognitive factors and subjects’ intention to take up the HPV vaccine. Results A total of 1,004 (83.7%) students aged 18 and 26 participated in this study. 23.3% found vaccinating for HPV acceptable, a level correlating with a number of indicators. Subjects were more likely to find vaccinating acceptable if 1) they knew something about HPV vaccines; 2) they understood that men were susceptible to infection by HPV; 3) they realised they could benefit by HPV vaccination, and 4) they were aware of the arguments for and against HPV vaccination, as disseminated by either the media or peers. Conclusions HPV remains a significant public health concern in Hong Kong and China more broadly. This study’s findings show a disconnect between the perceived and actual risk of being infected with the HPV vaccine among male baccalaureate students. This disconnect may be bridged by informing young men of the benefits of their being vaccinated against HPV, by removing the psychological and financial barriers that prevent them from taking up the vaccine and by improving how primary healthcare providers motivate them to get immunized. PMID:29912883

Estimation of the epidemiological burden of human papillomavirus-related cancers and non-malignant diseases in men in Europe: a review

PubMed Central

2012-01-01

Background The role of human papillomavirus (HPV) in malignant and non-malignant genital diseases in women is well known and the corresponding epidemiological burden has been widely described. However, less is known about the role of HPV in anal, penile and head and neck cancer, and the burden of malignant and non-malignant HPV-related diseases in men. The objective of this review is to estimate the epidemiological burden of HPV-related cancers and non-malignant diseases in men in Europe. Methods The annual number of new HPV-related cancers in men in Europe was estimated using Eurostat population data and applying cancer incidence rates published by the International Agency for Research on Cancer. The number of cancer cases attributable to HPV, and specifically to HPV16/18, was calculated based on the most relevant prevalence estimates. The annual number of new cases of genital warts was calculated from the most robust European studies; and latest HPV6/11 prevalence estimates were then applied. A literature review was also performed to retrieve exhaustive data on HPV infection at all anatomical sites under study, as well as incidence and prevalence of external genital warts, recurrent respiratory papillomatosis and HPV-related cancer trends in men in Europe. Results A total of 72, 694 new cancer cases at HPV-related anatomical sites were estimated to occur each year in men in Europe. 17,403 of these cancer cases could be attributable to HPV, with 15,497 of them specifically attributable to HPV16/18. In addition, between 286,682 and 325,722 new cases of genital warts attributable to HPV6/11were estimated to occur annually in men in Europe. Conclusions The overall estimated epidemiological burden of HPV-related cancers and non-malignant diseases is high in men in Europe. Approximately 30% of all new cancer cases attributable to HPV16/18 that occur yearly in Europe were estimated to occur in men. As in women, the vast majority of HPV-positive cancer in men is related to HPV16/18, while almost all HPV-related non-malignant diseases are due to HPV6/11. A substantial number of these malignant and non-malignant diseases may potentially be prevented by quadrivalent HPV vaccination. PMID:22260541

HPV in men.

PubMed

D'Hauwers, K W M; Tjalma, W A A

2008-01-01

To collect information about HPV in men and the (possible) correlation with HVP infection in women. Review of the literature. An overview of HPV-related penile and anal malignancies in men and the risk factors of acquiring HPV. In men HPV is also partially responsible for anogenital malignancies. Although the prevalence of HPV-related malignancies in men is much lower than in women, it is useful to gain more knowlege. Especially knowing if men are really the HPV reservoir and transmitters for women can make a difference in deciding whether men should also be screened for HPV and if they are good candidates for vaccination.

Role of Human Papillomavirus in Penile Carcinomas Worldwide.

PubMed

Alemany, Laia; Cubilla, Antonio; Halec, Gordana; Kasamatsu, Elena; Quirós, Beatriz; Masferrer, Emili; Tous, Sara; Lloveras, Belén; Hernández-Suarez, Gustavo; Lonsdale, Ray; Tinoco, Leopoldo; Alejo, Maria; Alvarado-Cabrero, Isabel; Laco, Jan; Guimerà, Nuria; Poblet, Enrique; Lombardi, Luis E; Bergeron, Christine; Clavero, Omar; Shin, Hai-Rim; Ferrera, Annabelle; Felix, Ana; Germar, Julieta; Mandys, Vaclav; Clavel, Christine; Tzardi, Maria; Pons, Luis E; Wain, Vincent; Cruz, Eugenia; Molina, Carla; Mota, Jose D; Jach, Robert; Velasco, Julio; Carrilho, Carla; López-Revilla, Ruben; Goodman, Marc T; Quint, Wim G; Castellsagué, Xavier; Bravo, Ignacio; Pawlita, Michael; Muñoz, Nubia; Bosch, F Xavier; de Sanjosé, Silvia

2016-05-01

Invasive penile cancer is a rare disease with an approximately 22 000 cases per year. The incidence is higher in less developed countries, where penile cancer can account for up to 10% of cancers among men in some parts of Africa, South America, and Asia. To describe the human papillomavirus (HPV) DNA prevalence, HPV type distribution, and detection of markers of viral activity (ie, E6*I mRNA and p16(INK4a)) in a series of invasive penile cancers and penile high-grade squamous intraepithelial lesions (HGSILs) from 25 countries. A total of 85 penile HGSILs and 1010 penile invasive cancers diagnosed from 1983 to 2011 were included. After histopathologic evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping were performed using the SPF-10/DEIA/LiPA25 system, v.1 (Laboratory Biomedical Products, Rijswijk, The Netherlands). HPV DNA-positive cases were additionally tested for oncogene E6*I mRNA and all cases for p16(INK4a) expression, a surrogate marker of oncogenic HPV activity. HPV DNA prevalence and type distributions were estimated. HPV DNA was detected in 33.1% of penile cancers (95% confidence interval [CI], 30.2-36.1) and in 87.1% of HGSILs (95% CI, 78.0-93.4). The warty-basaloid histologic subtype showed the highest HPV DNA prevalence. Among cancers, statistically significant differences in prevalence were observed only by geographic region and not by period or by age at diagnosis. HPV16 was the most frequent HPV type detected in both HPV-positive cancers (68.7%) and HGSILs (79.6%). HPV6 was the second most common type in invasive cancers (3.7%). The p16(INK4a) upregulation and mRNA detection in addition to HPV DNA positivity were observed in 69.3% of HGSILs, and at least one of these HPV activity markers was detected in 85.3% of cases. In penile cancers, these figures were 22.0% and 27.1%, respectively. About a third to a fourth of penile cancers were related to HPV when considering HPV DNA detection alone or adding an HPV activity marker, respectively. The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines in the reduction of HPV-related penile neoplastic lesions. About one-third to one-quarter of penile cancers were related to human papillomavirus (HPV). The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines to prevent HPV-related penile neoplastic lesions. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

The role of human papillomavirus infection in head and neck cancers.

PubMed

Syrjänen, S

2010-10-01

The link between head and neck squamous cell cancer (HNSCC), especially oropharyngeal cancer, and HPV has become established. HPV16 is the most common genotype in these tumours but HPV6 and HPV11 can also be found in a minority of these cancers, implying that these low-risk HPV types are not entirely benign in the head and neck region. HPV status is also associated with p16 expression and HPV+ tumours are less likely to harbour p53 mutations. HPV DNA is closely associated with poorly differentiated cancers, positive lymph nodes and late-stage disease, which all indicate poor prognosis. Contradictory to this, patients with HPV+ HNSCC seem to have significantly improved response to chemotherapy and radiotherapy as compared with HPV-negative tumours. Interestingly, the risk factors of HNSCC are the same as for HPV, including the number of sexual partners, younger age at first sexual intercourse, practice of oral sex, history of genital warts and younger age.

Human Papillomavirus (HPV) virion induced cancer and subfertility, two sides of the same coin

PubMed Central

Depuydt, CE; Beert, J; Bosmans, E; Salembier, G

2016-01-01

Abstract In the natural history of HPV infections, the HPV virions can induce two different pathways, namely the infec- tious virion producing pathway and the clonal transforming pathway. An overview is given of the burden that is associated with HPV infections that can both lead to cervical cancer and/or temporal subfertility. That HPV infections cause serious global health burden due to HPV-associated cancers is common knowledge, but that it is also responsible for a substantial part of idiopathic subfertility is greatly underestimated. The bulk of the detected HPV DNA whether in men or women is however infectious from origin. Because the dissociation between HPV viruses and HPV virions or infection and disease remains difficult for clinicians as well as for HPV detection, we propose a review of the different effects caused by the two different HPV virion induced pathways, and highlight the mechanisms that are responsible for causing transient subfertility and cancer. PMID:28210481

Immunological response to quadrivalent HPV vaccine in treatment of recurrent respiratory papillomatosis.

PubMed

Tjon Pian Gi, Robin E A; San Giorgi, Michel R M; Pawlita, Michael; Michel, Angelika; van Hemel, Bettien M; Schuuring, Ed M D; van den Heuvel, Edwin R; van der Laan, Bernard F A M; Dikkers, Frederik G

2016-10-01

Aim of this study was to explore influence of the quadrivalent HPV vaccine (Gardasil(®)) on the immune status of recurrent respiratory papillomatosis (RRP) patients. In retrospective observational study, six RRP patients who received the quadrivalent HPV vaccine and whose HPV seroreactivity was measured were included. Multiplex HPV Serology was used to determine HPV-specific antibodies pre- and post-vaccination. Surgical interventions and patient records were analyzed. Five HPV6 and 1 HPV11 infected patient were included. Mean antibody reactivity against the associated HPV type rose from 1125 median fluorescence intensity (MFI) pre-vaccination to 4690 MFI post-vaccination (p < 0.001). Median post-vaccination follow-up was 4 years. Poisson regression analysis showed that the quadrivalent HPV vaccine decreased the incidence rate of surgeries. The immune system of RRP patients is able to increase antibody reactivity against the associated HPV type. A double blind randomized controlled trial is needed to determine whether this immunological increase can cause decrease in number of surgeries.

The current state of therapeutic and T cell-based vaccines against human papillomaviruses

PubMed Central

Yang, Andrew; Farmer, Emily; Lin, John; Wu, T-C.; Hung, Chien-Fu

2016-01-01

Human papillomavirus (HPV) is known to be a necessary factor for many gynecologic malignancies and is also associated with a subset of head and neck malignancies. This knowledge has created the opportunity to control these HPV-associated cancers through vaccination. However, despite the availability of prophylactic HPV vaccines, HPV infections remain extremely common worldwide. In addition, while prophylactic HPV vaccines have been effective in preventing infection, they are ineffective at clearing pre-existing HPV infections. Thus, there is an urgent need for therapeutic and T cell-based vaccines to treat existing HPV infections and HPV-associated lesions and cancers. Unlike prophylactic vaccines, which generate neutralizing antibodies, therapeutic, and T cell-based vaccines enhance cell-mediated immunity against HPV antigens. Our review will cover various therapeutic and T cell-based vaccines in development for the treatment of HPV-associated diseases. Furthermore, we review the strategies to enhance the efficacy of therapeutic vaccines and the latest clinical trials on therapeutic and T cell-based HPV vaccines. PMID:27932207

Prevalence of human papillomavirus in anal and oral sites among patients with genital warts.

PubMed

Kofoed, Kristian; Sand, Carsten; Forslund, Ola; Madsen, Klaus

2014-03-01

Genital warts are caused by human papillomavirus (HPV). HPV is a leading cause of anogenital malignancies and a role of HPV in the aetiology of oro-pharyngeal cancers has been demonstrated. The frequency of oral HPV infection in patients with genital warts and the association between concomitant genital, anal and oral infection is unclear. A total of 201 men and women with genital wart-like lesions were recruited. Swab samples were obtained from the genital warts and the anal canal and an oral rinse was collected. Anal HPV was found in 46.2% and oral HPV in 10.4% of the participants. Concordance between anal and genital wart HPV types was 78.1%, while concordance between oral and genital wart types was 60.9%. A lower concordance of 21.7% was observed between anal and oral HPV types. Significantly more women than men had multiple HPV types and anal HPV. In conclusion, extra genital HPV is common in patients with genital warts. A gender inequality seems to exist.

Maternal Support for Human Papillomavirus Vaccination in Honduras

PubMed Central

Langrish, Sarah M.; Cotton, Deborah J.; Simon, Carol J.

2011-01-01

Abstract Background Cervical cancer is a leading cause of cancer death for women in Latin America, and vaccinating against human papillomavirus (HPV) has the potential to limit this disease. We sought to determine Honduran women's awareness of HPV vaccination and interest in vaccinating their daughters against HPV. Methods We interviewed mothers aged ≥17 at primary care clinics in Honduras. First, we collected demographic information and assessed knowledge related to cervical cancer prevention and awareness of HPV and HPV vaccination. Because most participants were not familiar with HPV, education about the relationships among HPV, sexual activity, and cervical cancer was provided before we asked participants if they would accept HPV vaccination for a 9-year-old daughter. We used multivariable logistic regression to determine predictors of vaccine acceptance. Results We interviewed 632 mothers. Only 13% had heard of HPV vaccination before the interview. After education, 91% would accept HPV vaccination for a 9-year-old daughter. Mothers who intended to vaccinate knew more at baseline about cervical cancer prevention than did those who did not endorse vaccination. Demographic characteristics did not predict vaccine acceptance. Conclusions Few Honduran mothers were aware of HPV or HPV vaccination. However, most Honduran mothers would accept HPV vaccination for their daughters after receiving education about the relationship between HPV infection and cervical cancer. Baseline cervical cancer knowledge was associated with vaccine acceptance. PMID:21091226

Genital HPV infection and related lesions in men

PubMed Central

Anic, Gabriella M.; Giuliano, Anna R.

2012-01-01

Human papillomavirus (HPV) is highly prevalent in men and there is an interest in further understanding the relationship between HPV infection and disease in men, including the development of genital warts, penile intraepithelial neoplasia and invasive penile carcinomas. Genital warts are caused by HPV 6/11 and are the most common clinical manifestation of HPV in men. Though they are benign and not associated with mortality, they are a source of psychosocial distress and physical discomfort. HPV infection can also develop into invasive penile carcinoma which is associated with morbidity and mortality. Approximately 40% of invasive penile carcinomas are attributable to HPV with HPV 16, 18, and 6/11 being the genotypes most commonly detected in penile tumors. Penile carcinomas of the basaloid and warty histologic subtypes are most likely to test positive for HPV. In addition to HPV infection, the risk factors most strongly associated with penile cancer are lack of neonatal circumcision, phimosis (the inability of uncircumcised men to fully retract the foreskin), and anogenital warts. Male vaccination with the quadrivalent HPV vaccine that protects against HPV 6/11/16/18 has been shown to significantly reduce HPV-associated anogenital infection and disease in men. If the quadrivalent vaccine is successfully disseminated to large segments of the young male population, there is the potential for substantial reduction in genital HPV infection and related lesions in men. PMID:21962470

Prevalence of Human Papillomavirus in Women from Mexico City

PubMed Central

López Rivera, María Guadalupe; Flores, Maria Olivia Medel; Villalba Magdaleno, José D'Artagnan; Sánchez Monroy, Virginia

2012-01-01

Introduction. Cervical cancer is the most common cancer among Mexican women. The goal of the present study was to determine the prevalence and distribution of HPV types in women from Mexico City. Methods. Our study was conducted in the Clinica de Especialidades de la Mujer de la Secretaría de la Defensa Nacional, Mexico. Random samples were taken from 929 healthy women requesting a cervical Papanicolaou examination. Detection and genotyping of HPV were performed by multiplex PCR, with the HPV4A ACE Screening kit (Seegene). Results. 85 of nine hundred twenty-nine women (9.1%) were infected with HPV. Of HPV-positive women, 99% and 1% had high- and low-risk HPV genotypes, respectively. The prevalence of the 16 high-risk (HR) HPV types that were screened was 43% : 42% (18) were HPV positive and 14% (16) were HPV positive, which includes coinfection. Multiple infections with different viral genotypes were detected in 10% of the positive cases. Abnormal cervical cytological results were found in only 15.3% of HPV-positive women, while 84.7% had normal cytological results. Conclusions. We found a similar prevalence of HPV to previous studies in Mexico. The heterogeneity of the HPV genotype distribution in Mexico is evident in this study, which found a high frequency of HPV HR genotypes, the majority of which were HPV 18. PMID:22811590

Prevalence and clinical utility of human papilloma virus genotyping in patients with cervical lesions.

PubMed

Kaur, Parminder; Aggarwal, Aruna; Nagpal, Madhu; Oberoi, Loveena; Sharma, Swati

2014-08-01

Cervical cancer is the commonest cancer among Indian women. High-risk human papilloma virus (HPV) detection holds the potential to be used as a tool to identify women, at risk of subsequent development of cervical cancer. There is a pressing need to identify prevalence of asymptomatic cervical HPV infection in local population. In our study, we explored the prevalence of HPV genotypes and their distribution in women with cervical lesions. Scrape specimens were obtained from 100 women (study group) with cervical abnormalities. HPV was detected with amplicor HPV tests, and the individual genotypes in these specimens were identified by Hybribio Genoarray test kit. Fifty specimens were also collected from females with healthy cervix (control group). The present study also aimed to determine the status of HPV prevalence and its association with different sociodemographic factors. Out of the total number of 100 samples, 10 (10 %) women tested positive for HPV DNA. Among them, HPV 18 was observed in 6, HPV 16 in 2, HPV 52 and HPV 39 in one each. Fifty specimens collected from patients with healthy cervix were not infected with any of the HPV genotype. Our study generates data of HPV prevalence in patients with cervical lesions visiting tertiary care institute. The data generated will be useful for laying guidelines for mass screening of HPV detection, treatment, and prophylaxis.

An analysis of HPV infection incidence and clearance by genotype and age in men: The HPV Infection in Men (HIM) Study.

PubMed

Ingles, Donna J; Lin, Hui-Yi; Fulp, William J; Sudenga, Staci L; Lu, Beibei; Schabath, Matthew B; Papenfuss, Mary R; Abrahamsen, Martha E; Salmeron, Jorge; Villa, Luisa L; Ponce, Eduardo Lazcano; Giuliano, Anna R

2015-12-01

Genital HPV infection in men causes benign and cancerous lesions, the incidence of which differs by age. The goal of this work was to comprehensively evaluate incidence and clearance of individual HPV genotypes among men by age group. HIV-negative men ages 18-70 with no history of anogenital cancer were recruited for the HPV Infection in Men (HIM) Study . Participants completed clinical exams and questionnaires every six months for up to ~4 years. Genital specimens underwent HPV genotyping, with associations between age and HPV assessed using Cox analyses. 4085 men were followed for a median of 48.6 months (range: 0.3-94.0). Significantly lower HPV incidence rates were observed among the oldest age group (55-70 years) for grouped high-risk (incidence rate ratio [IRR]=0.71), HPV16 (IRR=0.54), grouped low-risk (IRR=0.74), and HPV6 (IRR=0.57) infections compared to men ages 18-24. However, incidence of the grouped 9-valent HPV vaccine types remained constant across the lifespan. Likelihood of HPV6 and HPV16 clearance remained constant until age 54, then increased significantly for men ages 55-70 (adjusted hazard ratio [AHR]=1.92 and 1.65, respectively). Men remain susceptible to HPV infections throughout their lifespan, highlighting the need for prevention efforts with long-lasting duration.

Amplification of human papillomavirus early genes for detection of nine genotypes in Venezuelan women.

PubMed

Michelli, Elvia; Téllez, Luis; Mendoza, José-Andrés; Noguera, María-Eugenia; Milano, Melisse; Vera, Reauben; Callejas, Diana

2013-12-01

Genotyping of human papillomavirus (HPV) by molecular methods may enhance assessment information for screening and following of cervical infection. In this study, cervical samples were obtained from 250 women, along with colposcopic and cytological evaluations. A Nested-PCR-Multiplex assay was used for HPV detection and genotyping for HPV E6/E7 early regions. Infection with HPV was detected in 26.0% of the samples, with 98.46% positive for at least one genotype. High-risk HPVs were identified in 98.44%. HPV18 infection was detected in 76.92% of samples and HPV16 in 36.92%, whether as individual or as multiple infections. These infections were seen more frequently in women under 35 years of age (64.7%). The Pap-smear examination showed that 16.92% (11/65) of the samples had cervical changes suggesting HPV infection, whereas the colposcopic evaluation was suggestive of HPV infection in 47.69% (31/65) of DNA-HPV positive samples. There was a high frequency of high-risk HPV genotypes, particularly HPV18, alone or in multiple-type infections. Colposcopy findings showed to have a high predictive value for the diagnosis of HPV infection. The results reflect that over 50% of HPV-positive patients had a normal colposcopy and/or cytology, highlighting the importance of including HPV testing along with genotype identification in routine gynecological evaluations.

Characteristics of human papillomaviruses infection in men with genital warts in Shanghai.

PubMed

Chen, Xiaogang; Li, Liang; Lai, Yongxian; Liu, Qinxiu; Yan, Jianna; Tang, Yichen

2016-08-16

Human papillomaviruses (HPV) infected men causes continued transmission of HPV to women. The prevalence of 15 high-risk HPV strains (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68) and 6 low-risk HPV strains (HPV6, 11, 42, 43, 44 and CP8304) were evaluated in 935 males with genital warts. Of the 447 (447/935, 47.8%) HPV DNA positive subjects, 230 (24.6%), 356 (38.1%) and 139 (14.9%) were infected by high-risk, low-risk and both high and low-risk HPV respectively. Of the 356 low-risk HPV infected subjects, 333(93.5%) were infected by single HPV strain; 203 (57.0%), 147 (41.3%), 24 (6.7%) and 5 (1.4%) were infected with HPV genotype 6, 11, CP8304 and 44 respectively; population with age ≤ 20 showed the highest infection rate. High-risk HPV are also highly prevalent in our patients, genotype 16, 58, 51, 39, 52 and 53 are the top five prevalent genotypes with infection rates of 27.4%, 18.7%, 14.3%, 13.9%, 12.6% and 12.6% respectively; only 68.3% subjects were sole infection; subjects with 41 ≤ age ≤ 50 showed the highest infection rate. Both high and low-risk HPV are highly prevalent in men with genital warts, its impact on women HPV control and prevention need further evaluation.

Human papillomavirus burden in different cancers in Iran: a systematic assessment.

PubMed

Jalilvand, Somayeh; Shoja, Zabihollah; Hamkar, Rasool

2014-01-01

Certain types of human papillomaviruses (HPVs) are undoubtedly involved in genesis of human malignancies. HPV plays an etiological role in cervical cancer, but also in many vaginal, vulvar, anal and penile cancers, as well as head and neck cancers. In addition, a number of non-malignant diseases such as genital warts and recurrent respiratory papillomatosis are attributable to HPV. Moreover, HPV forms have detected in several other cancers including esophageal squamous cell carcinoma, lung, prostate, ovarian, breast, skin, colorectal and urinary tract cancers, but associations with etiology in these cases is controversial. The aim of this systematic assessment was to estimate the prevalence of HPV infection and HPV types in HPV-associated cancers, HPV-related non-malignant diseases and in cancers that may be associated with HPV in Iran. The present investigation covered 61 studies on a variety of cancers in Iranian populations. HPV prevalence was 77.5 % and 32.4% in cervical cancer and head and neck cancers, respectively. HPV was detected in 23.1%, 22.2%, 10.4%, 30.9%, 14% and 25.2% of esophageal squamous cell, lung, prostate, urinary tract cancers, breast and skin cancers, respectively. HPV16 and 18 were the most frequent HPV types in all cancers. The findings of present study imply that current HPV vaccines for cervical cancer may decrease the burden of other cancers if they are really related to HPV.

[Human papillomavirus and penile cancer : Thinking about measures for prevention].

PubMed

Schneede, P; Schlenker, B

2018-04-01

Two major pathways of penile carcinogenesis are known: human papillomavirus (HPV)-induced penile cancer and HPV-negative cancers associated with chronic dermatoses. Therefore, modern measures for prevention of penile cancer may for example include prophylactic HPV vaccination. The resulting B‑cell-mediated immunity to HPV capsid proteins is effective protection against future HPV infections. Contrarily when treating existing HPV infections or HPV-associated cancers an antigen-specific T‑cell immunity is necessary. To date, screening and treatment of precancerous lesions to prevent penile cancer are not established in the German health care program and the highly expected therapeutic HPV vaccines are still on the horizon. In this article, we focus on possible strategies to prevent HPV-related penile cancer on different levels of carcinogenesis.

Broad HPV distribution in the genital region of men from the HPV infection in men (HIM) study.

PubMed

Sichero, Laura; Pierce Campbell, Christine M; Ferreira, Silvaneide; Sobrinho, João S; Luiza Baggio, Maria; Galan, Lenice; Silva, Roberto C; Lazcano-Ponce, Eduardo; Giuliano, Anna R; Villa, Luisa L

2013-09-01

The HPV infection in men (HIM) study examines the natural history of genital HPV infection in men. Genotyping methods used in this study identify 37 α-HPV types; however, the viral type could not be identified in approximately 22% of male genital specimens that were HPV PCR positive. Our aim was to genotype HPV-unclassified specimens by sequencing PGMY09/11, GP5+/6+ or FAP59/64 PCR products. Using this approach we were able to detect 86 unique HPV types among 508 of 931 specimens analyzed. We report for the first time the presence of a broad range of α-, β- and γ-HPV at the male genitals. Copyright © 2013 Elsevier Inc. All rights reserved.

Long linear MWIR and LWIR HgCdTe infrared detection arrays for high resolution imaging

NASA Astrophysics Data System (ADS)

Chamonal, Jean-Paul; Audebert, Patrick; Medina, Philippe; Destefanis, Gérard; Deschamps, Joel R.; Girard, Michel; Chatard, Jean-Pierre

2018-04-01

This paper, "Long linear MWIR and LWIR HgCdTe infrared detection arrays for high resolution imaging," was presented as part of International Conference on Space Optics—ICSO 1997, held in Toulouse, France.

New fabrication of high-frequency (100-MHz) ultrasound PZT film kerfless linear array.

PubMed

Zhu, Benpeng; Chan, Ngai Yui; Dai, Jiyan; Shung, K Kirk; Takeuchi, Shinichi; Zhou, Qifa

2013-04-01

The paper describes the design, fabrication, and measurements of a high-frequency ultrasound kerfless linear array prepared from hydrothermal lead zirconate titanate (PZT) thick film. The 15-μm hydrothermal PZT thick film with an area of 1 × 1 cm, obtained through a self-separation process from Ti substrate, was used to fabricate a 32-element 100-MHz kerfless linear array with photolithography. The bandwidth at -6 dB without matching layer, insertion loss around center frequency, and crosstalk between adjacent elements were measured to be 39%, -30 dB, and -15 dB, respectively.

Linear-array based full-view high-resolution photoacoustic computed tomography of whole mouse brain functions in vivo

NASA Astrophysics Data System (ADS)

Li, Lei; Zhang, Pengfei; Wang, Lihong V.

2018-02-01

Photoacoustic computed tomography (PACT) is a non-invasive imaging technique offering high contrast, high resolution, and deep penetration in biological tissues. We report a photoacoustic computed tomography (PACT) system equipped with a high frequency linear array for anatomical and functional imaging of the mouse whole brain. The linear array was rotationally scanned in the coronal plane to achieve the full-view coverage. We investigated spontaneous neural activities in the deep brain by monitoring the hemodynamics and observed strong interhemispherical correlations between contralateral regions, both in the cortical layer and in the deep regions.

[Association of human papillomavirus infection with other microbial pathogens in gynecology].

PubMed

Zheng, Mei-yun; Zhao, He-lan; Di, Jun-ping; Lin, Gan; Lin, Ying; Lin, Xi; Zheng, Min-qiao

2010-06-01

To Investigate correlation between screening assay of human papillomavirus (HPV) and microbial pathogens in gynecology. Cervical samples were collected to search for HPV, bacteria and yeast infections in gynecologic outpatients. HPV typing was carried out by PCR and sequencing on cervical brush specimens. Chlamydia trachomatis was identified by strand displacement amplification (SDA) and the other microorganisms were detected by conventional methods. All data were analyzed to investigate the correlation among them. In this cross-sectional study, among 857 enrolled outpatients, there were 266 cases with positive HPV DNA, and the rate of infection was 31.0% (266/857). HPV genotype showed that thirty-five different HPV types were identified, of which HPV16 was the most prevalent (14.5%, 38/262), followed by HPV58 (9.2%, 24/262), HPV53 (8.0%, 21/262) and HPV42 (6.1%, 16/262); while other genotypes were present in less than 5% of HPV positive women. According to the reclassification, the aggregated percentage (high-risk and probably high-risk) of detected HPV was 58.8% (154/262), 27.9% (73/262) for low-risk and 13.4% (35/262) for unknown-risk HPV types. Among HPV positive women, cervical brush specimens results showed that more than 60% cases with normal cytology, 3.8% (10/266) with high-grade squamous intraepithelial lesions (HSIL), 29.7% (79/266) with low-grade squamous intraepithelial lesions (LSIL) and 3.0% (8/266) with atypical squamous cells of undetermined significance (ASCUS), respectively. Statistical analyses revealed there was a significant association between the infected HPV and Chlamydia trachomatis or Ureaplasma urealyticum (> 10,000 CCU/ml; all P < 0.01), while no correlation was found between HPV infection and bacterial vaginosis, streptococcus agalactiae, candida, Trichomonas vaginalis or Ureaplasma urealyticum (≤ 10 000 CCU/ml; all P > 0.05). Among the cases with bacterial vaginosis, the positive rate of HPV infected was 42.6%. Chlamydia trachomatis was one of the high-risk factors for the infection of HPV (OR = 2.82, 95% CI: 1.74 - 4.57). Mycoplasma hominis was isolated only in 2 cases, no patient was infected with Neisseria gonorrhoeae. Although bacterial vaginosis was not significantly associated with HPV, it was more common among the HPV positive women. There is the significant association between HPV and Chlamydia trachomatis or Ureaplasma urealyticum which may be increase the infection of HPV. These data suggest that it may be important to screen for the simultaneous presence of different microorganisms which may have synergistic pathological effects.

Primary screening for cervical cancer based on high-risk human papillomavirus (HPV) detection and HPV 16 and HPV 18 genotyping, in comparison to cytology.

PubMed

Agorastos, Theodoros; Chatzistamatiou, Kimon; Katsamagkas, Taxiarchis; Koliopoulos, George; Daponte, Alexandros; Constantinidis, Theocharis; Constantinidis, Theodoros C

2015-01-01

The objective of the present study is to assess the performance of a high-risk human papillomavirus (HR-HPV) DNA test with individual HPV-16/HPV-18 genotyping as a method for primary cervical cancer screening compared with liquid-based cytology (LBC) in a population of Greek women taking part in routine cervical cancer screening. The study, conducted by the "HEllenic Real life Multicentric cErvical Screening" (HERMES) study group, involved the recruitment of 4,009 women, aged 25-55, who took part in routine cervical screening at nine Gynecology Departments in Greece. At first visit cervical specimens were collected for LBC and HPV testing using the Roche Cobas 4800 system. Women found positive for either cytology or HPV were referred for colposcopy, whereas women negative for both tests will be retested after three years. The study is ongoing and the results of the first screening round are reported herein. Valid results for cytology and HPV testing were obtained for 3,993 women. The overall prevalence of HR-HPV was 12.7%, of HPV-16 2.7% and of HPV-18 1.4%. Of those referred for colposcopy, cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was detected in 41 women (1.07%). At the threshold of CIN2+, cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] and HPV testing showed a sensitivity of 53.7% and 100% respectively, without change between age groups. Cytology and HPV testing showed specificity of 96.8% and 90.3% respectively, which was increased in older women (≥30) in comparison to younger ones (25-29). Genotyping for HPV16/18 had similar accuracy to cytology for the detection of CIN2+ (sensitivity: 58.5%; specificity 97.5%) as well as for triage to colposcopy (sensitivity: 58.5% vs 53.7% for cytology). HPV testing has much better sensitivity than cytology to identify high-grade cervical lesions with slightly lower specificity. HPV testing with individual HPV-16/HPV-18 genotyping could represent a more accurate methodology for primary cervical cancer screening in comparison to liquid-based cytology, especially in older women.

Cost-effectiveness of HPV-based cervical cancer screening in the public health system in Nicaragua.

PubMed

Campos, Nicole G; Mvundura, Mercy; Jeronimo, Jose; Holme, Francesca; Vodicka, Elisabeth; Kim, Jane J

2017-06-15

To evaluate the cost-effectiveness of human papillomavirus (HPV) DNA testing (versus Papanicolaou (Pap)-based screening) for cervical cancer screening in Nicaragua. A previously developed Monte Carlo simulation model of the natural history of HPV infection and cervical cancer was calibrated to epidemiological data from Nicaragua. Cost data inputs were derived using a micro-costing approach in Carazo, Chontales and Chinandega departments; test performance data were from a demonstration project in Masaya department. Nicaragua's public health sector facilities. Women aged 30-59 years. Screening strategies included (1) Pap testing every 3 years, with referral to colposcopy for women with an atypical squamous cells of undetermined significance or worse result ('Pap'); (2) HPV testing every 5 years, with referral to cryotherapy for HPV-positive eligible women (HPV cryotherapy or 'HPV-Cryo'); (3) HPV testing every 5 years, with referral to triage with visual inspection with acetic acid (VIA) for HPV-positive women ('HPV-VIA'); and (4) HPV testing every 5 years, with referral to Pap testing for HPV-positive women ('HPV-Pap'). Reduction in lifetime risk of cancer and incremental cost-effectiveness ratios (ICER; 2015 US$ per year of life saved (YLS)). HPV-based screening strategies were more effective than Pap testing. HPV-Cryo was the least costly and most effective strategy, reducing lifetime cancer risk by 29.5% and outperforming HPV-VIA, HPV-Pap and Pap only, which reduced cancer risk by 19.4%, 12.2% and 10.8%, respectively. With an ICER of US$320/YLS, HPV-Cryo every 5 years would be very cost-effective using a threshold based on Nicaragua's per capita gross domestic product of US$2090. Findings were robust across sensitivity analyses on test performance, coverage, compliance and cost parameters. HPV testing is very cost-effective compared with Pap testing in Nicaragua, due to higher test sensitivity and the relatively lower number of visits required. Increasing compliance with recommended follow-up will further improve the health benefits and value for public health dollars. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Pathogenic role of the eight probably/possibly carcinogenic HPV types 26, 53, 66, 67, 68, 70, 73 and 82 in cervical cancer.

PubMed

Halec, Gordana; Alemany, Laia; Lloveras, Belen; Schmitt, Markus; Alejo, Maria; Bosch, Franz X; Tous, Sara; Klaustermeier, Jo Ellen; Guimerà, Nuria; Grabe, Niels; Lahrmann, Bernd; Gissmann, Lutz; Quint, Wim; Bosch, Francesc X; de Sanjose, Silvia; Pawlita, Michael

2014-12-01

Eight HPV types (HPV26, 53, 66, 67, 68, 70, 73 and 82) that are phylogenetically closely related to 12 WHO-defined high-risk (HR) HPV have been rarely but consistently identified as single HPV infections in about 3% of cervical cancer (CxCa) tissues. Due to lack of biological data, these types are referred to as probable/possible (p) HR-HPV. To analyse their biological activity in direct comparison to HR-HPV types, we selected 55 formalin-fixed, paraffin-embedded (FFPE) CxCa tissues harbouring single pHR-HPV infections (2-13 cases per type) and 266 tissues harbouring single HR-HPV (7-40 cases per type) from a worldwide, retrospective, cross-sectional study. Single HPV infection was verified by two genotyping methods. Presence of type-specific spliced E6*I mRNA transcripts and expression of cellular proteins indicative of HPV transformation were assessed in all cases. In 55 CxCa tissues with pHR-HPV, E6*I mRNA expression was 100%; high p16(INK4a) , 98%; low pRb, 96%; low CyD1, 93%; and low p53, 84%. Compared to HPV16 tissues as a reference, individual frequencies of these five markers did not differ significantly, either for any of the eight pHR-HPV and the 11 other HR types individually or for the groups of pHR and HR types without HPV16. We conclude that the eight pHR-HPV types, when present as a single infection in CxCa, are biologically active and affect the same cellular pathways as any of the fully recognized carcinogenic HR-HPV types. Therefore we have provided molecular evidence of carcinogenicity for types currently classified as probably/possibly carcinogenic. Although this evidence is crucial for HPV-type carcinogenicity classification, per se it is not sufficient for inclusion of these HPV types into population-wide primary and secondary prevention programmes. Such decisions have to include careful estimation of effectiveness and cost-benefit analyses. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Characterization of Two Novel Gammapapillomaviruses, HPV179 and HPV184, Isolated from Common Warts of a Renal-Transplant Recipient

PubMed Central

Hošnjak, Lea; Kocjan, Boštjan J.; Pirš, Branko; Seme, Katja; Poljak, Mario

2015-01-01

Gammapapillomavirus (Gamma-PV) is a diverse and rapidly expanding PV-genus, currently consisting of 76 fully characterized human papillomavirus (HPV) types. In this study, DNA genomes of two novel HPV types, HPV179 and HPV184, obtained from two distinct facial verrucae vulgares specimens of a 64 year-old renal-transplant recipient, were fully cloned, sequenced and characterized. HPV179 and HPV184 genomes comprise 7,228-bp and 7,324-bp, respectively, and contain four early (E1, E2, E6 and E7) and two late genes (L1 and L2); the non-coding region is typically positioned between L1 and E6 genes. Phylogenetic analysis of the L1 nucleotide sequence placed both novel types within the Gamma-PV genus: HPV179 was classified as a novel member of species Gamma-15, additionally containing HPV135 and HPV146, while HPV184 was classified as a single member of a novel species Gamma-25. HPV179 and HPV184 type-specific quantitative real-time PCRs were further developed and used in combination with human beta-globin gene quantitative real-time PCR to determine the prevalence and viral load of the novel types in the patient’s facial warts and several follow-up skin specimens, and in a representative collection, a total of 569 samples, of HPV-associated benign and malignant neoplasms, hair follicles and anal and oral mucosa specimens obtained from immunocompetent individuals. HPV179 and HPV184 viral loads in patients’ facial warts were estimated to be 2,463 and 3,200 genome copies per single cell, respectively, suggesting their active role in the development of common warts in organ-transplant recipients. In addition, in this particular patient, both novel types had established a persistent infection of the skin for more than four years. Among immunocompetent individuals, HPV179 was further detected in low-copy numbers in a few skin specimens, indicating its cutaneous tissue tropism, while HPV184 was further detected in low-copy numbers in one mucosal and a few skin specimens, suggesting its dual tissue tropism. PMID:25748516

[Results of the first human papilloma virus center in Hungary (2007-2011)].

PubMed

Galamb, Adám; Pajor, Attila; Langmár, Zoltán; Sobel, Gábor

2011-11-06

Human papilloma virus (HPV) is the most common sexually transmitted infection in the 21st century. It has been established that infections with specific HPV types are contributing factors to cervical cancer. Approximately 99.7% of cervical cancers are associated with high risk HPV types. HPV testing plays an important role in the prevention, by decreasing the prevalence and the mortality of cervical cancer. There are 16 HPV-centers operating in Hungary, in which patients undergo HPV screening, cervical exams, and treatment based on standardized guidelines. The first HPV-center was founded in 2007 in Budapest, at the 2nd Department of Obstetrics and Gynecology, Semmelweis University. This study aimed to define the presence and prevalence of HPV-DNA in the cervical swab samples obtained from patients in our center. Authors conducted to assess the age-specific-prevalence, and HPV type distribution, the associated cervical abnormalities, comparing our results with international data. Overall 1155 woman underwent HPV-testing and genotyping, using polymerase chain reaction. Overall, 55.5% of patients had positive test for HPV DNA types, in which 38.5% for high-risk HPV DNA. Overall prevalence was the highest among females aged 15 to 25 years (62.9%). The most common HPV type found was the high risk type 16 (19.5% among the patients with positive HPV testing). Presence of high risk HPV with concurrent cervical cytological abnormality was in 32%. More than two-thirds of woman with cytological atypia (70.6%) were infected with two or more high risk HPV types. HPV 16 was detected in 32% of patients with cytological abnormalities. The results suggest that the prevalence of HPV in this study population exceeds the international data. The results attracts the attention the peak prevalence of the high risk types in the youngest age-group, and the higher risk of cervical abnormality in case of presence of two or more HPV types. The dominance of type 16 and 18 was predictable, but the strong attendance of type 51 and 31 among patients who had cytological atypia, was slightly surprising.