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Sample records for high-risk human papillomaviruses

  1. Prevalence of High-Risk Human Papillomavirus Among Older Women

    PubMed Central

    Lindau, Stacy Tessler; Drum, Melinda L.; Gaumer, Elyzabeth; Surawska, Hanna; Jordan, Jeanne A.

    2009-01-01

    Objective To estimate the prevalence, genotypes, and individual-level correlates of high-risk human papillomavirus (HPV) among women aged 57–85. Methods Community-residing women (n=1550), aged 57–85, were drawn from a nationally-representative probability sample. In-home interviews and biomeasures, including a self-collected vaginal specimen, were obtained between 2005 and 2006. Specimens were analyzed for high-risk HPV DNA using probe hybridization and signal amplification (hc2); of 1,028 specimens provided, 1,010 were adequate for analysis. All samples testing positive were analyzed for HPV DNA by L1 consensus polymerase chain reaction followed by type-specific hybridization. Results The overall population-based weighted estimate of high-risk HPV prevalence by hc2 was 6.0% (95% confidence interval [CI] = 4.5 to 7.9). Current marital and smoking status, frequency of sexual activity, history of cancer, and hysterectomy were associated with high-risk HPV positivity. Among high-risk HPV+ women, 63% had multiple type infections. HPV 16 or 18 was present in 17.4% of all high-risk HPV+ women. The most common high-risk genotypes among high-risk HPV+ women were HPV 61 (19.1%), 31 (13.1%), 52 (12.9%), 58 (12.5%), 83 (12.3%), 66(12.0%), 51 (11.7%), 45 (11.2%), 56 (10.3%), 53 (10.2%), 16 (9.7%), and 62 (9.2%). Being married and having an intact uterus were independently associated with lower prevalence of high-risk HPV. Among unmarried women, current sexual activity and smoking were independently and positively associated with high-risk HPV infection. Conclusions In this nationally representative population, nearly 1 in 16 women aged 57–85 were found to have high-risk HPV and prevalence was stable across older age groups. PMID:18978096

  2. High-Risk Human Papillomavirus Targets Crossroads in Immune Signaling

    PubMed Central

    Tummers, Bart; Van Der Burg, Sjoerd H.

    2015-01-01

    Persistent infections with a high-risk type human papillomavirus (hrHPV) can progress to cancer. High-risk HPVs infect keratinocytes (KCs) and successfully suppress host immunity for up to two years despite the fact that KCs are well equipped to detect and initiate immune responses to invading pathogens. Viral persistence is achieved by active interference with KCs innate and adaptive immune mechanisms. To this end hrHPV utilizes proteins encoded by its viral genome, as well as exploits cellular proteins to interfere with signaling of innate and adaptive immune pathways. This results in impairment of interferon and pro-inflammatory cytokine production and subsequent immune cell attraction, as well as resistance to incoming signals from the immune system. Furthermore, hrHPV avoids the killing of infected cells by interfering with antigen presentation to antigen-specific cytotoxic T lymphocytes. Thus, hrHPV has evolved multiple mechanisms to avoid detection and clearance by both the innate and adaptive immune system, the molecular mechanisms of which will be dealt with in detail in this review. PMID:26008697

  3. Distribution and attribution of high-risk human papillomavirus genotypes in cervical precancerous lesions in China.

    PubMed

    Wang, Wenpeng; An, Jusheng; Song, Yan; Wang, Minjie; Huang, Manni; Wu, Lingying

    2017-07-01

    While human papillomavirus vaccine was recently approved by China Food and Drug Administration, mapping of high-risk human papillomavirus distribution and attribution in cervical precancerous lesions in China becomes critical in development of a high-risk human papillomavirus-based cervical cancer screening and prevention strategy. In total, 1016 patients with cervical precancerous lesions diagnosed in the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences were analyzed retrospectively, including 111 patients with low-grade squamous intraepithelial lesions and 905 patients with high-grade squamous intraepithelial lesions. HPV16, 58, 52, 33, and 31 were the most common high-risk human papillomavirus genotypes in order of decreasing frequency among high-risk human papillomavirus-positive high-grade squamous intraepithelial lesions; this differed from the high-risk human papillomavirus distribution in low-grade squamous intraepithelial lesions (HPV16, 52, 39, 56, and 58). The distribution of high-risk human papillomavirus genotypes in single-type infections for high-grade squamous intraepithelial lesions (HPV16, 58, 33, and 52) was similar to that in multiple-type infections (HPV16, 58, 52, and 33). By contrast, a more diverse distribution spectrum of high-risk human papillomavirus genotypes for low-grade squamous intraepithelial lesions was observed between single-type (HPV16, 52, 39, and 56) and multiple-type infection (HPV52, 68, 58, 59, 39 and 56). A previously published method was adopted to calculate the fractional proportion of individual high-risk human papillomavirus genotypes in multiple infections. For this proportional attribution, HPV16 (48.9%), 58 (10.0%), 33 (5.5%), and 52 (5.5%) were the most frequent among all high-grade squamous intraepithelial lesions, whereas HPV16 (13.2%), 52 (11.6%), 39 (9.5%), and 56 (7.6%) were the most frequent among all low-grade squamous intraepithelial lesions. Differences in high-risk human

  4. High risk human papillomavirus and Epstein Barr virus in human breast milk

    PubMed Central

    2012-01-01

    Background Multiple viruses, including human immunodeficiency virus, Epstein Barr virus (EBV) and mouse mammary tumour virus have been identified in human milk. High risk human papillomavirus (HPV) sequences have been identified in breast cancer. The aim of this study is to determine if viral sequences are present in human milk from normal lactating women. Findings Standard (liquid) and in situ polymerase chain reaction (PCR) techniques were used to identify HPV and EBV in human milk samples from normal lactating Australian women who had no history of breast cancer. High risk human papillomavirus was identified in milk samples of 6 of 40 (15%) from normal lactating women - sequencing on four samples showed three were HPV 16 and one was HPV 18. Epstein Barr virus was identified in fourteen samples (33%). Conclusion The presence of high risk HPV and EBV in human milk suggests the possibility of milk transmission of these viruses. However, given the rarity of viral associated malignancies in young people, it is possible but unlikely, that such transmission is associated with breast or other cancers. PMID:22937830

  5. Molecular Characterization of High-Risk Human Papillomavirus in Women in Bobo-Dioulasso, Burkina Faso.

    PubMed

    Traore, Ina Marie Angèle; Zohoncon, Théodora Mahoukèdè; Dembele, Adama; Djigma, Florencia W; Obiri-Yeboah, Dorcas; Traore, Germain; Bambara, Moussa; Ouedraogo, Charlemagne; Traore, Yves; Simpore, Jacques

    2016-01-01

    High-risk human papillomavirus (HPV) is found in over 99% of cervical cancers. The aim of this study was to determine the prevalence of HPV in a population of women in Bobo-Dioulasso and to identify the high-risk types present in these women. From May to June, 2015, 181 women who came for consultation at the Souro Sanou University Hospital of Bobo-Dioulasso have been included in this study. Uterine endocervical swabs have been taken in these women. DNA obtained by extraction from the samples thus collected was used to determine the prevalence of high-risk human papillomavirus genotypes through real-time PCR. The age of the women ranged from 20 to 56 years with a mean of 35.3 ± 8.1 years. The prevalence of infection by high-risk HPV types was 25.4% (46/181). The most common high-risk HPV genotypes were HPV 39 (18.5%), HPV 52 (16.7%), HPV 18 (14.8%), and HPV 35 (13.0%). HPV 16 which is included in the HPV vaccines was not found in the population studied. This type of study which is the first one in Bobo-Dioulasso has showed a high prevalence of genotypes HPV 39, HPV 52, and HPV 35 which are not yet covered by a vaccine.

  6. Molecular Characterization of High-Risk Human Papillomavirus in Women in Bobo-Dioulasso, Burkina Faso

    PubMed Central

    Traore, Ina Marie Angèle; Dembele, Adama; Obiri-Yeboah, Dorcas; Traore, Germain; Bambara, Moussa; Ouedraogo, Charlemagne; Traore, Yves

    2016-01-01

    High-risk human papillomavirus (HPV) is found in over 99% of cervical cancers. The aim of this study was to determine the prevalence of HPV in a population of women in Bobo-Dioulasso and to identify the high-risk types present in these women. From May to June, 2015, 181 women who came for consultation at the Souro Sanou University Hospital of Bobo-Dioulasso have been included in this study. Uterine endocervical swabs have been taken in these women. DNA obtained by extraction from the samples thus collected was used to determine the prevalence of high-risk human papillomavirus genotypes through real-time PCR. The age of the women ranged from 20 to 56 years with a mean of 35.3 ± 8.1 years. The prevalence of infection by high-risk HPV types was 25.4% (46/181). The most common high-risk HPV genotypes were HPV 39 (18.5%), HPV 52 (16.7%), HPV 18 (14.8%), and HPV 35 (13.0%). HPV 16 which is included in the HPV vaccines was not found in the population studied. This type of study which is the first one in Bobo-Dioulasso has showed a high prevalence of genotypes HPV 39, HPV 52, and HPV 35 which are not yet covered by a vaccine. PMID:27525275

  7. Methylation of SFRPs and APC genes in ovarian cancer infected with high risk human papillomavirus.

    PubMed

    Al-Shabanah, Othman Abdulla; Hafez, Mohamed Mahmoud; Hassan, Zeinab Korany; Sayed-Ahmed, Mohamed Mohamed; Abozeed, Waleed Nabeel; Alsheikh, Abdulmalik; Al-Rejaie, Salem Saleh

    2014-01-01

    Secreted frizzled-related protein (SFRP) genes, new tumor suppressor genes, are negative regulators of the Wnt pathway whose alteration is associated with various tumors. In ovarian cancer, SFRPs genes promoter methylation can lead to gene inactivation. This study investigated mechanisms of SFRP and adenomatous polyposis coli (APC) genes silencing in ovarian cancer infected with high risk human papillomavirus. DNA was extracted from 200 formalin-fixed paraffin-embedded ovarian cancer and their normal adjacent tissues (NAT) and DNA methylation was detected by methylation specific PCR (MSP). High risk human papillomavirus (HPV) was detected by nested PCR with consensus primers to amplify a broad spectrum of HPV genotypes. The percentages of SFRP and APC genes with methylation were significantly higher in ovarian cancer tissues infected with high risk HPV compared to NAT. The methylated studied genes were associated with suppression in their gene expression. This finding highlights the possible role of the high risk HPV virus in ovarian carcinogenesis or in facilitating cancer progression by suppression of SFRP and APC genes via DNA methylation.

  8. High-risk human papillomavirus and cervical lymph node metastasis in patients with oropharyngeal cancer.

    PubMed

    Joo, Young-Hoon; Jung, Chan-Kwon; Sun, Dong-Il; Park, Jun-Ook; Cho, Kwang-Jae; Kim, Min-Sik

    2012-01-01

    The purpose of this study was to determine the role of high-risk human papillomavirus (HPV) in lymph node metastasis and the depth of invasion in oropharyngeal cancer. The study included patients with 90 oral carcinomas and 66 oropharyngeal carcinomas. High-risk HPV in situ hybridization was performed to detect HPV infection. The positive rate of high-risk HPV in situ hybridization was 15.4% (24 of 156). There was a significant difference in the fraction of positive high-risk HPV between oral (6.7%) and oropharyngeal (27.3%) cancers (p < .000). Significant correlations were found between positive high-risk HPV and cervical lymph node metastasis, tumor depth of invasion in patients with oropharyngeal cancer (p = .002, p = .016, respectively). There was a statistically significant association between high-risk HPV positivity and the disease-specific survival in patients with oropharyngeal cancer (p = .035). High-risk HPV infection was significantly related to cervical lymph node metastasis and depth of invasion in patients with oropharyngeal cancer. © 2011 Wiley Periodicals, Inc. Head Neck, 2012. Copyright © 2011 Wiley Periodicals, Inc.

  9. Prediction of high-risk types of human papillomaviruses using statistical model of protein "sequence space".

    PubMed

    Wang, Cong; Hai, Yabing; Liu, Xiaoqing; Liu, Nanfang; Yao, Yuhua; He, Pingan; Dai, Qi

    2015-01-01

    Discrimination of high-risk types of human papillomaviruses plays an important role in the diagnosis and remedy of cervical cancer. Recently, several computational methods have been proposed based on protein sequence-based and structure-based information, but the information of their related proteins has not been used until now. In this paper, we proposed using protein "sequence space" to explore this information and used it to predict high-risk types of HPVs. The proposed method was tested on 68 samples with known HPV types and 4 samples without HPV types and further compared with the available approaches. The results show that the proposed method achieved the best performance among all the evaluated methods with accuracy 95.59% and F1-score 90.91%, which indicates that protein "sequence space" could potentially be used to improve prediction of high-risk types of HPVs.

  10. Easy and fast detection and genotyping of high-risk human papillomavirus by dedicated DNA microarrays.

    PubMed

    Albrecht, Valérie; Chevallier, Anne; Magnone, Virginie; Barbry, Pascal; Vandenbos, Fanny; Bongain, André; Lefebvre, Jean-Claude; Giordanengo, Valérie

    2006-11-01

    Persistent cervical high-risk human papillomavirus (HPV) infection is correlated with an increased risk of developing a high-grade cervical intraepithelial lesion. A two-step method was developed for detection and genotyping of high-risk HPV. DNA was firstly amplified by asymmetrical PCR in the presence of Cy3-labelled primers and dUTP. Labelled DNA was then genotyped using DNA microarray hybridization. The current study evaluated the technical efficacy of laboratory-designed HPV DNA microarrays for high-risk HPV genotyping on 57 malignant and non-malignant cervical smears. The approach was evaluated for a broad range of cytological samples: high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL) and atypical squamous cells of high-grade (ASC-H). High-risk HPV was also detected in six atypical squamous cells of undetermined significance (ASC-US) samples; among them only one cervical specimen was found uninfected, associated with no histological lesion. The HPV oligonucleotide DNA microarray genotyping detected 36 infections with a single high-risk HPV type and 5 multiple infections with several high-risk types. Taken together, these results demonstrate the sensitivity and specificity of the HPV DNA microarray approach. This approach could improve clinical management of patients with cervical cytological abnormalities.

  11. Genotype distribution characteristics of high-risk human papillomaviruses in women from Shanghai, China.

    PubMed

    Gu, Y; Yi, M; Xu, Y; Zhao, H; Fu, F; Zhang, Y

    2016-05-01

    High-risk human papillomaviruses (HPVs) are highly prevalent worldwide, and HPV genotype distribution varies regionally. Molecular surveys of HPVs are important for effective HPV control and prevention. Fifteen high-risk HPV strains (16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68) and six low-risk HPV strains (HPV6, 11, 42, 43, 44, CP8304) were detected by cervical cytology from 10 501 subjects. High-risk HPVs, low-risk HPVs, and both high- and low-risk HPVs were detected in 14·5%, 2·8%, and 2·4% of cases, respectively. Of 1782 subjects with high-risk HPV infection, 75·5%, 18·1%, and 6·4% were infected with one, two, and ⩾3 strains of high-risk HPVs, respectively. HPV52, HPV16, and HPV58 were the top three most dominant high-risk HPV genotypes in our population with positivity rates of 23·0%, 17·7% and 16·9%, respectively. Multiple infection was common, with significantly higher co-infection rates of HPV58/HPV33 (12·9%) and HPV58/HPV52 (11·3%). Further data comparisons showed that HPV genotype distribution varied markedly between domestic and international regions. In conclusion, a monolithic vaccination strategy is obviously impractical, and regional HPV surveillance is essential to optimize current HPV control and prevention.

  12. 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

  13. Branchiogenic carcinoma with high-risk-type human papillomavirus infection: A case report

    PubMed Central

    Maeda, Hiroyuki; Deng, Zeyi; Ikegami, Taro; Matayoshi, Sen; Agena, Shinya; Kiyuna, Asanori; Yamashita, Yukashi; Uehara, Takayuki; Ganaha, Akira; Suzuki, Mikio

    2016-01-01

    Branchiogenic carcinoma (BC) usually appears as a mass lesion with a predominant cystic component. Since lymph node metastasis from oropharyngeal carcinoma (OPC) has a cystic appearance, it is occasionally difficult to distinguish between BC and nodal metastases from clinically silent OPC. Factors associated with the malignant transformation process in BC remain obscure. The present study reports the case of a 56-year-old man with a right cystic cervical mass that was diagnosed as squamous cell carcinoma based on examination by fine-needle aspiration biopsy. The primary tumor could not be detected despite several imaging examinations, a pan-endoscopy of the head and neck, esophagus and stomach, biopsies of the head and neck regions, and bilateral tonsillectomies. The pathological findings of the surgical specimens from a radical neck dissection were consistent with the histological characteristics of BC, with evidence of transition from dysplasia through intraepithelial carcinoma to invasive carcinoma. Normal squamous epithelium and dysplastic and cancerous portions in the BC showed strong p16INK4a immunoreactivity. The expression of p16INK4a was also observed in all 9 nodal metastases in the neck dissection specimens. The cystic formation observed in the BC was not observed in the nodal metastases. As the presence of human papillomavirus-16 in the tumor was confirmed by polymerase chain reaction, quantitative polymerase chain reaction was employed for the measurement of human papillomavirus-16 viral load and integration. The results showed that the viral load of human papillomavirus-16 was 3.01×107/50 ng genomic DNA, and the E2/E6 ratio was 0.13, so the integration state was judged to be the mixed type. To the best of our knowledge, this is the first report of BC associated with high-risk-type human papillomavirus infection. The study indicates that a human papillomavirus-positive neck mass may not necessarily be OPC, but that it could be BC with a poor prognosis

  14. High-Risk Human Papillomavirus E7 Proteins Target PTPN14 for Degradation

    PubMed Central

    Münger, Karl; Howley, Peter M.

    2016-01-01

    ABSTRACT The major transformation activity of the high-risk human papillomaviruses (HPV) is associated with the E7 oncoprotein. The interaction of HPV E7 with retinoblastoma family proteins is important for several E7 activities; however, this interaction does not fully account for the high-risk E7-specific cellular immortalization and transformation activities. We have determined that the cellular non-receptor protein tyrosine phosphatase PTPN14 interacts with HPV E7 from many genus alpha and beta HPV types. We find that high-risk genus alpha HPV E7, but not low-risk genus alpha or beta HPV E7, is necessary and sufficient to reduce the steady-state level of PTPN14 in cells. High-risk E7 proteins target PTPN14 for proteasome-mediated degradation, which requires the ubiquitin ligase UBR4, and PTPN14 is degraded by the proteasome in HPV-positive cervical cancer cell lines. Residues in the C terminus of E7 interact with the C-terminal phosphatase domain of PTPN14, and interference with the E7-PTPN14 interaction restores PTPN14 levels in cells. Finally, PTPN14 degradation correlates with the retinoblastoma-independent transforming activity of high-risk HPV E7. PMID:27651363

  15. Association of high-risk human papillomavirus infection with oral epithelial dysplasia.

    PubMed

    McCord, Christina; Xu, Jing; Xu, Wei; Qiu, Xin; McComb, Richard John; Perez-Ordonez, Bayardo; Bradley, Grace

    2013-04-01

    The aim of this study was to evaluate cases of oral epithelial dysplasia for biologically significant human papillomavirus (HPV) infection. Forty consecutive cases of high-grade dysplasia and 37 cases of low-grade dysplasia were examined for p16(INK4a) expression by immunohistochemistry. High-risk HPV infection was assessed in p16-positive cases using in situ hybridization. Proliferation index was assessed with MIB-1 immunohistochemistry. Eleven of 40 high-grade dysplasias and one of 37 low-grade dysplasias were p16 positive. High-risk HPV was detected in seven cases of p16-positive high-grade dysplasia. The difference between high- and low-grade dysplasia was statistically significant (P = .01). HPV-positive high-grade dysplasias showed a distinctive histologic appearance and MIB-1 labeling pattern. Most high-risk HPV-positive cases were seen in the floor of mouth. High-risk HPV was associated with a subset of cases of severe epithelial dysplasia/carcinoma in situ that demonstrated diffuse loss of squamous differentiation and a high proliferation index. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Detection of High-Risk Human Papillomaviruses in the Prevention of Cervical Cancer in India.

    PubMed

    Baskaran, Krishnan; Kumar, P Kranthi; Karunanithi, Santha; Sethupathy, Subramanian; Thamaraiselvi, B; Swaruparani, S

    2015-01-01

    Human papillomaviruses (HPVs) are small, non-enveloped, double-stranded DNA viruses that infect epithelial tissues. Specific genotypes of human papillomavirus are the single most common etiological agents of cervical intraepithelial lesions and cervical cancer. Cervical cancer usually arises at squamous metaplastic epithelium of transformation zone (TZ) of the cervix featuring infection with one or more oncogenic or high-risk HPV (HR- HPV) types. A hospital- based study in a rural set up was carried out to understand the association of HR-HPV with squamous intraepithelial lesions (SILs) and cervical cancer. In the present study, HR-HPV was detected in 65.7% of low-grade squamous intraepithelial lesions (LSILs), 84.6% of high-grade squamous intraepithelial lesions (HSILs) and 94% of cervical cancer as compared to 10.7% of controls. The association of HPV infection with SIL and cervical cancer was analyzed with Chi square test (p<0.001). The significant association found confirmed that detection of HR-HPV is a suitable candidate for early identification of cervical precancerous lesions and in the prevention of cervical cancer in India.

  17. Dynamics of high-risk nonvaccine human papillomavirus types after actual vaccination scheme.

    PubMed

    Peralta, Raúl; Vargas-De-León, Cruz; Cabrera, Augusto; Miramontes, Pedro

    2014-01-01

    Human papillomavirus (HPV) has been identified as the main etiological factor in the developing of cervical cancer (CC). This finding has propitiated the development of vaccines that help to prevent the HPVs 16 and 18 infection. Both genotypes are associated with 70% of CC worldwide. In the present study, we aimed to determine the emergence of high-risk nonvaccine HPV after actual vaccination scheme to estimate the impact of the current HPV vaccines. A SIR-type model was used to study the HPV dynamics after vaccination. According to the results, our model indicates that the application of the vaccine reduces infection by target or vaccine genotypes as expected. However, numerical simulations of the model suggest the presence of the phenomenon called vaccine-induced pathogen strain replacement. Here, we report the following replacement mechanism: if the effectiveness of cross-protective immunity is not larger than the effectiveness of the vaccine, then the high-risk nonvaccine genotypes emerge. In this scenario, further studies of infection dispersion by HPV are necessary to ascertain the real impact of the current vaccines, primarily because of the different high-risk HPV types that are found in CC.

  18. Dynamics of High-Risk Nonvaccine Human Papillomavirus Types after Actual Vaccination Scheme

    PubMed Central

    Peralta, Raúl; Vargas-De-León, Cruz; Cabrera, Augusto; Miramontes, Pedro

    2014-01-01

    Human papillomavirus (HPV) has been identified as the main etiological factor in the developing of cervical cancer (CC). This finding has propitiated the development of vaccines that help to prevent the HPVs 16 and 18 infection. Both genotypes are associated with 70% of CC worldwide. In the present study, we aimed to determine the emergence of high-risk nonvaccine HPV after actual vaccination scheme to estimate the impact of the current HPV vaccines. A SIR-type model was used to study the HPV dynamics after vaccination. According to the results, our model indicates that the application of the vaccine reduces infection by target or vaccine genotypes as expected. However, numerical simulations of the model suggest the presence of the phenomenon called vaccine—induced pathogen strain replacement. Here, we report the following replacement mechanism: if the effectiveness of cross-protective immunity is not larger than the effectiveness of the vaccine, then the high-risk nonvaccine genotypes emerge. In this scenario, further studies of infection dispersion by HPV are necessary to ascertain the real impact of the current vaccines, primarily because of the different high-risk HPV types that are found in CC. PMID:24803952

  19. Low prevalence of high risk human papillomavirus in normal oral mucosa by hybrid capture 2

    PubMed Central

    González-Losa, Maria del Refugio; Manzano-Cabrera, Luis; Rueda-Gordillo, Florencio; Hernández-Solís, Sandra E.; Puerto-Solís, Luis

    2008-01-01

    High risk human papillomavirus (HR-HPV) are recognized as a necessary factor to development cervical cancer. During the last decade many studies have found HR-HPV in oral squamous cell carcinoma (OSCC) and normal oral mucosa, however the association between HR-HPV and OSCC is still uncertain. The aim of the study was to determine DNA HR-HPV in normal oral cavity of healthy adults. A cross-sectional study was performed; samples from 77 patients with normal oral cavity were collected at the Dentistry school, Autonomous University of Yucatan, Merida, Yucatan, México. HR-HPV was detected by hybrid capture 2. One sample out of 77(1.2%) was positive for HR-PVH. It was from a man of 50 years old. HRHPV is present in low rate among healthy oral mucosa. Hybrid capture 2 could be a good methodology for large epidemiology studies. PMID:24031173

  20. Small cell neuroendocrine carcinomas of the lung do not harbor high-risk human papillomavirus.

    PubMed

    Hartley, Christopher P; Steinmetz, Heather B; Memoli, Vincent A; Tafe, Laura J

    2015-04-01

    High-risk subtypes of the human papillomavirus (HPV) are known to drive the pathogenesis of cervical, anogenital, and oropharyngeal squamous cell carcinomas. Recent reports have shown that HPV is also associated with small cell neuroendocrine carcinomas of the cervix and oropharynx. Little is known about HPV as a driver of neuroendocrine tumors at other sites, in particular, small cell lung cancer (SCLC). The aim of this study was to evaluate SCLC for the presence of high-risk HPV to further elucidate the role of HPV in SCLC. Archived formalin-fixed, paraffin-embedded surgical resection specimens from 20 primary SCLC from 19 patients were identified from 2004 to 2013. Two cervical small cell carcinomas were included as controls. Small cell neuroendocrine phenotype was confirmed by review of morphology and prior immunohistochemistry staining. Immunohistochemistry for p16 (INK4a) expression was performed in all cases. DNA was extracted from formalin-fixed, paraffin-embedded specimens and run on the Roche Linear Array HPV Genotyping test and a real-time polymerase chain reaction HPV assay. Pathologic tumor stage was collected from surgical pathology reports. High-risk HPV genotypes were not detected in any of the 20 SCLC specimens, whereas p16 was up-regulated in 14 (70%) of 20. p16 up-regulation can be used as an indicator of disruption of the Rb pathway either by integration of the HPV E7 oncoprotein or other mechanisms. In conclusion, our findings indicate that, unlike some other small cell neuroendocrine carcinomas, the pathogenesis of SCLC does not appear to be associated with high-risk HPV infection, a potentially very useful characteristic when determining primary from metastatic tumors. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Electrochemical chip-based genomagnetic assay for detection of high-risk human papillomavirus DNA.

    PubMed

    Bartosik, Martin; Durikova, Helena; Vojtesek, Borivoj; Anton, Milan; Jandakova, Eva; Hrstka, Roman

    2016-09-15

    Cervical cancer, being the fourth leading cause of cancer death in women worldwide, predominantly originates from a persistent infection with a high-risk human papillomavirus (HPV). Detection of DNA sequences from these high-risk strains, mostly HPV-16 and HPV-18, represents promising strategy for early screening, which would help to identify women with higher risk of cervical cancer. In developing countries, inadequate screening options lead to disproportionately high mortality rates, making a fast and inexpensive detection schemes highly important. Electrochemical sensors and assays offer an alternative to current methods of detection. We developed an electrochemical-chip based assay, in which target HPV DNA is captured via magnetic bead-modified DNA probes, followed by an antidigoxigenin-peroxidase detection system at screen-printed carbon electrode chips, enabling parallel measurements of eight samples simultaneously. We show sensitive detection in attomoles of HPV DNA, selective discrimination between HPV-16 and HPV-18 and good reproducibility. Most importantly, we show application of the assay into both cancer cell lines and cervical smears from patients. The electrochemical results correlated well with standard methods, making this assay potentially applicable in clinical practice. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Prevalence of high-risk human papillomavirus infection in women with ovarian endometriosis.

    PubMed

    Heidarpour, Mitra; Derakhshan, Maryam; Derakhshan-Horeh, Marzieh; Kheirollahi, Majid; Dashti, Sepideh

    2017-01-01

    In this study, we aimed to determine the prevalence of human papillomavirus (HPV) in ovarian endometriosis and ovarian tissue from women without endometriosis. Understanding the pathogenesis of the disease could help us design preventative strategies as well as novel and appropriate treatment approaches in this regard. In this cross-sectional study, formalin-fixed and paraffin-embedded tissue sections from 50 and 49 ovaries with and without endometriosis, respectively, were evaluated for the presence of high-risk HPV using the polymerase chain reaction technique. Prevalence of HPV infection and other related characteristics of the studied population were compared. High-risk HPV infection was detected in 13 (26%) and five (10.2%) of the samples with and without endometriosis, respectively (P = 0.041, χ(2)  = 3.16). Mean age and parity were not significantly different in subjects with and without HPV infection in the two studied groups (P = 0.7 and P = 0.06 for age in case and control groups, respectively; and P = 0.32 and P = 0.09 for parity in case and control groups, respectively). The results of our study indicated a higher rate of high-risk HPV infection among patients with endometriosis. The findings could provide us baseline information for future studies regarding the pathogenesis of endometriosis and the role of viral infection and their possible impact on future cancer development in this group of patients. © 2016 Japan Society of Obstetrics and Gynecology.

  3. Infection and integration of high-risk human papillomavirus in HPV-associated cancer cells.

    PubMed

    Liu, Chu-Yi; Li, Fan; Zeng, Yi; Tang, Min-zhong; Huang, Yulu; Li, Jin-Tao; Zhong, Ru-Gang

    2015-04-01

    High-risk human papillomaviruses (HPV) have been associated with many human cancers in clinical studies. Integration of HPV into the human genome is a suspected etiological factor in the induction of some HPV-associated cancers. The characteristics of HPV integration in certain HPV-integrated cancer cells remain unclear. In this study, ten HPV-associated carcinoma cell lines were evaluated for the presence, genotype, and integration status of HPV by nested polymerase chain reaction. The HPV genome did not insert in the genome of a mammary cancer cell line (MCF7), adrenal neuroblastoma cell line (NH-6), or three esophageal carcinoma cell lines (KYSE150, KYSE450 and KYSE140). HPV type 18 DNA did infect cell lines of tongue cancer (Tca83), hepatocellular carcinoma (Hep G2), and lung carcinoma (A549), but the HPV type 18 genes were not transcribed into mRNA. However, HPV type 18 integrated into the genomes of the esophageal carcinoma cell lines EC9706 and EC109, and the integration sites for both cell lines were in loci 8q24, which is a gene desert area adjacent to fragile sites. We speculate that HPV transcripts are more likely to integrate near highly susceptible fragile sites. This study suggests that HPV integration is still a significant issue that needs to be fully examined and can possibly be used as individualized biomarkers for the early diagnosis of HPV-related cancers.

  4. High-risk human papillomavirus infection involving multiple anatomic sites of the female lower genital tract: a multiplex real-time polymerase chain reaction-based study.

    PubMed

    Hui, Yiang; Manna, Pradip; Ou, Joyce J; Kerley, Spencer; Zhang, Cunxian; Sung, C James; Lawrence, W Dwayne; Quddus, M Ruhul

    2015-09-01

    High-risk human papillomavirus infection usually is seen at one anatomic site in an individual. Rarely, infection at multiple anatomic sites of the female lower genital tract in the same individual is encountered either simultaneously and/or at a later date. The current study identifies the various subtypes of high-risk human papillomavirus infection in these scenarios and analyzes the potential significance of these findings. High-risk human papillomavirus infection involving 22 anatomic sites from 7 individuals was identified after institutional review board approval. Residual paraffin-embedded tissue samples were retrieved, and all 15 high-risk human papillomavirus were identified and viral load quantified using multiplex real-time polymerase chain reaction-based method. Multiple high-risk human papillomavirus subtypes were identified in 32% of the samples and as many as 5 different subtypes of high-risk human papillomavirus infection in a single anatomic site. In general, each anatomic site has unique combination of viral subtypes, although one individual showed overlapping subtypes in the vagina, cervix, and vulvar samples. Higher viral load and rare subtypes are more frequent in younger patients and in dysplasia compared with carcinoma. Follow-up ranging from 3 to 84 months revealed persistent high-risk human papillomavirus infection in 60% of cases. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Evidence of disrupted high-risk human papillomavirus DNA in morphologically normal cervices of older women.

    PubMed

    Leonard, Sarah M; Pereira, Merlin; Roberts, Sally; Cuschieri, Kate; Nuovo, Gerard; Athavale, Ramanand; Young, Lawrence; Ganesan, Raji; Woodman, Ciarán B

    2016-02-15

    High-risk human papillomavirus (HR-HPV) causes nearly 100% of cervical carcinoma. However, it remains unclear whether HPV can establish a latent infection, one which may be responsible for the second peak in incidence of cervical carcinoma seen in older women. Therefore, using Ventana in situ hybridisation (ISH), quantitative PCR assays and biomarkers of productive and transforming viral infection, we set out to provide the first robust estimate of the prevalence and characteristics of HPV genomes in FFPE tissue from the cervices of 99 women undergoing hysterectomy for reasons unrelated to epithelial abnormality. Our ISH assay detected HR-HPV in 42% of our study population. The majority of ISH positive samples also tested HPV16 positive using sensitive PCR based assays and were more likely to have a history of preceding cytological abnormality. Analysis of subsets of this population revealed HR-HPV to be transcriptionally inactive as there was no evidence of a productive or transforming infection. Critically, the E2 gene was always disrupted in those HPV16 positive cases which were assessed. These findings point to a reservoir of transcriptionally silent, disrupted HPV16 DNA in morphologically normal cervices, re-expression of which could explain the increase in incidence of cervical cancer observed in later life.

  6. Detection of high-risk human papillomavirus infection in tonsillar specimens using 2 commercially available assays.

    PubMed

    Cockerill, Cara C; Orvidas, Laura J; Moore, Eric J; Binnicker, Matthew J; Duresko, Brian J; Espy, Mark J; Cockerill, Franklin R; Tombers, Nicole M; Pritt, Bobbi S

    2016-12-01

    THE OBJECTIVE OF THE STUDY IS TO DETERMINE THE PREVALENCE OF HIGH-RISK HUMAN PAPILLOMAVIRUS (HRHPV) INFECTION IN TONSILLAR SWABS AND TISSUE: Patients undergoing tonsillectomy for nonmalignant causes were enrolled. A flocked swab and fresh tissue were collected from the left and right tonsil of each patient. Specimens were tested for hrHPV DNA using the Roche cobas test and for the presence of E6/E7 messenger RNA using the Hologic Aptima hrHPV test. Of the 193 patients enrolled, 129 were in the pediatric group (ages 1-12years; median, 5years), and 64 were in the adult group (ages 13-55; median, 22years). All swab and tissue specimens were negative for hrHPV by both methods. Positive, negative, and internal controls performed as expected. We found a 0% rate of infection indicating that detectable hrHPV infection in tonsillar tissue appears to be uncommon in the children and adults in the population sampled. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Decreased prevalence of high-risk human papillomavirus infection is associated with obesity.

    PubMed

    Jung, U S; Choi, J S; Ko, J H; Lee, J H; Park, S Y; Park, S H

    2013-01-01

    Obesity is correlated with low education, low economic status, and lower rates of Pap smears, which are known as socio-demographic risk factors for cervical cancer. However, the association between obesity and high-risk human papillomavirus (HR-HPV) infection, the necessary cause of cervical cancer, and its related precursors, is not established. The authors examined the association between obesity and HR-HPV infection in 6,868 patients, who participated in annual health examinations at the Kangbuk Samsung Hospital in Seoul, Korea, from January through December 2007. The prevalence of HR-HPV infection was 14.8%. Women infected with HR-HPV had a lower body mass index (BMI), when compared with non-infected women. After adjustment for alcohol intake, cigarette smoking, and marital status, HR-HPV infection was found to be negatively associated with BMI. When the analysis was stratified according to BMI, the risk of HR-HPV infection was significantly lower among those who were overweight (OR = 0.817, 95% CI = 0.680-0.982), or obese (OR = 0.688, 95% CI = 0.556-0.851), when compared with women with normal weight. HR-HPV infection was associated with obesity defined by BMI, with a lower prevalence of infection observed in obese women.

  8. Molecular evidence of high-risk human papillomavirus infection in colorectal tumours from Cuban patients

    PubMed Central

    Soto, Yudira; Limia, Celia Maria; González, Licet; Grá, Bienvenido; Hano, Olga Marina; Martínez, Pedro Ariel; Kourí, Vivian

    2016-01-01

    The association between colorectal cancer and human papillomavirus (HPV) infection is still unproven. The aim of this study was to investigate the presence of high-risk HPV (HR-HPV) DNA in colorectal tissues from Cuban patients. A total of 63 colorectal formalin-fixed paraffin-embedded tissues were studied (24 adenocarcinoma, 18 adenoma, and 21 colorectal tissues classified as benign colitis). DNA from colorectal samples was analysed by quantitative real-time polymerase chain reaction to detect the most clinically relevant high HR-HPV types (HPV-16, -18, -31, -33, -45, -52, and -58). Associations between histologic findings and other risk factors were also analysed. Overall, HPV DNA was detected in 23.8% (15/63) of the samples studied. Viral infections were detected in 41.7% of adenocarcinoma (10/24) and 27.7% of adenoma cases (5/18). HPV DNA was not found in any of the negative cases. An association between histological diagnosis of adenocarcinoma and HPV infection was observed (odd ratio = 4.85, 95% confidence interval = 1.40-16.80, p = 0.009). The only genotypes identified were HPV 16 and 33. Viral loads were higher in adenocarcinoma, and these cases were associated with HPV 16. This study provides molecular evidence of HR-HPV infection in colorectal adenocarcinoma tissues from Cuban patients. PMID:27812599

  9. High-risk human papillomavirus in Galicia, Spain: prevalence and evaluation of the sample representativeness.

    PubMed

    Trigo-Daporta, Matilde; García-Campello, Marta; Pérez-Ríos, Monica; Santiago-Pérez, Maria Isolina; Fernandez-Rodriguez, Eva; Guinarte, Genoveva; Troncoso, Ana; Pardavila, Raquel; Malvar, Alberto

    2014-11-01

    The prevalence of high-risk genotypes of the human papillomavirus (HR-HPV) in Galicia remained unknown before the introduction of the HPV vaccine. The objective of this study was to estimate this prevalence in non-vaccinated women when vaccination against HR-HPV started. Sample representativeness was also evaluated. Female volunteers aged 16-64 years, residents in Galicia, Spain, completed a questionnaire and provided biological samples for a virological study and for cytology. The sample was weighted; prevalence rates were estimated and are shown with 95% confidence intervals. Virological results were available for 1703 women. HR-HPV prevalence was 10.1%, decreasing notably at ages above 30 years. HPV-16 was the most frequent genotype and 3.6% of women were infected by more than one genotype. No adjustment was necessary to generalize the results of the study. In Galicia in 2009 there would be 96 400 women aged 16-64 years infected with HR-HPV. It is possible to estimate HR-HPV prevalence in a population starting from a volunteer sample.

  10. Association of High Risk Human Papillomavirus and Breast cancer: A UK based Study

    PubMed Central

    Salman, Nadia Aziz; Davies, Giles; Majidy, Farida; Shakir, Fatima; Akinrinade, Hilda; Perumal, Dhayaneethie; Ashrafi, G. Hossein

    2017-01-01

    Infection by human papillomaviruses (HPVs) has been implicated in the aetiology of a variety of cancers. Studies evaluating the presence of HPVs in breast cancer (BC) have generated considerable controversy. To date, most studies have focused on the presence of viral DNA in BC; however there are important gaps in evidencing the role of HPV persistence in the invasiveness of BC. While these studies have been conducted in several countries, none, on the presence and biological activity of high risk (HR) HPV in BC has been done in the UK. Hence, we aimed to investigate these gaps by screening a total of 110 fresh breast tissue specimens from UK patients for the presence of twelve HR-HPV types DNA using PCR and Sanger sequencing. Samples positive for HPV-DNA were screened for viral oncoprotein expression using western blot and dot blot. Data obtained showed the presence of HR-HPVs in 42% of breast tissues of which the viral activity was only confirmed in a number of invasive carcinomas (5/26). This finding, the first to report in the UK, suggests that the selective expression of viral oncoprotein in invasive cases may propose a role for HR-HPVs in the development of some types of BC. PMID:28240743

  11. Do high-risk human papillomaviruses cause oral cavity squamous cell carcinoma?

    PubMed

    Mirghani, H; Amen, F; Moreau, F; Lacau St Guily, J

    2015-03-01

    High-risk human papillomaviruses (HR-HPV) are an established etiologic factor for a growing number of oropharyngeal cancers. However, their potential role in other upper aerodigestive tract locations is still a matter of debate, particularly in the oral cavity. This is of paramount importance as in the future diagnosis, treatment and follow up in head and neck squamous cell carcinoma may vary according to HPV status. This article reviews the recent published data and highlights some of the pitfalls that have hampered the accurate assessment of HR-HPV oncological role outside the oropharynx. We demonstrate that, in contrast to the oropharynx, only a small fraction of cancers located in the oral cavity seem to be HPV-related even in young non-smoking non-drinking patients. We emphasize several relevant factors to consider in assumed HPV-induced oral cavity cancers and discuss the current theories that explain why HPV-induced cancers arise preferentially in the oropharynx. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Low- and high-risk human papillomavirus E7 proteins regulate p130 differently

    SciTech Connect

    Barrow-Laing, Lisa; Chen Wei; Roman, Ann

    2010-05-10

    The E7 protein of high-risk human papillomaviruses (HR HPVs) targets pRb family members (pRb, p107 and p130) for degradation; low-risk (LR) HPV E7 only targets p130 for degradation. The effect of HR HPV 16 E7 and LR HPV 6 E7 on p130 intracellular localization and half-life was examined. Nuclear/cytoplasmic fractionation and immunofluorescence showed that, in contrast to control and HPV 6 E7-expressing cells, a greater amount of p130 was present in the cytoplasm in the presence of HPV 16 E7. The half-life of p130, relative to control cells, was decreased in the cytoplasm in the presence of HPV 6 E7 or HPV 16 E7, but only decreased by HPV 6 E7 in the nucleus. Inhibition of proteasomal degradation extended the half-life of p130, regardless of intracellular localization. These results suggest that there may be divergent mechanisms by which LR and HR HPV E7 target p130 for degradation.

  13. First-void urine: A potential biomarker source for triage of high-risk human papillomavirus infected women.

    PubMed

    Van Keer, Severien; Pattyn, Jade; Tjalma, Wiebren A A; Van Ostade, Xaveer; Ieven, Margareta; Van Damme, Pierre; Vorsters, Alex

    2017-09-01

    Great interest has been directed towards the use of first-void urine as a liquid biopsy for high-risk human papillomavirus DNA testing. Despite the high correlations established between urinary and cervical infections, human papillomavirus testing is unable to distinguish between productive and transforming high-risk infections that have the tendency to progress to cervical cancer. Thus far, investigations have been primarily confined to the identification of biomarkers for triage of high-risk human papillomavirus-positive women in cervicovaginal specimens and tissue biopsies. This paper reviews urinary biomarkers for cervical cancer and triage of high-risk human papillomavirus infections and elaborates on the opportunities and challenges that have emerged regarding the use of first-void urine as a liquid biopsy for the analysis of both morphological- (conventional cytology and novel immunohistochemical techniques) and molecular-based (HPV16/18 genotyping, host/viral gene methylation, RNA, and proteins) biomarkers. A literature search was performed in PubMed and Web of Science for studies investigating the use of urine as a biomarker source for cervical cancer screening. Five studies were identified reporting on biomarkers that are still in preclinical exploratory or clinical assay development phases and on assessments of non-invasive (urine) samples. Although large-scale validation studies are still needed, we conclude that methylation of both host and viral genes in urine has been proven feasible for use as a molecular cervical cancer triage and screening biomarker in phase two studies. This is especially promising and underscores our hypothesis that human papillomavirus DNA and candidate human and viral biomarkers are washed away with the initial, first-void urine, together with exfoliated cells, debris and impurities that line the urethra opening. Similar to the limitations of self-collected cervicovaginal samples, first-void urine will likely not fulfil the

  14. Co-prevalence of Epstein-Barr virus and high-risk human papillomaviruses in Syrian women with breast cancer.

    PubMed

    Al Moustafa, Ala-Eddin; Al-Antary, Noor; Aboulkassim, Tahar; Akil, Nizar; Batist, Gerald; Yasmeen, Amber

    2016-07-02

    ABSTRAT We recently performed 2 studies viewing the presence of Epstein-Barr virus (EBV) and high-risk human papillomaviruses (HPVs) types 16, 18, 31, 33 and 35 in human breast cancer in the Syrian population. Herein, we report that EBV and high-risk HPVs are co-present in breast cancer in Syrian women. Therefore, and based on our previous studies and present data, we reveal that 35 (32%) of 108 cancer samples are positive for both EBV and high-risk HPVs and their co-presence is associated with high grade invasive ductal carcinomas (IDCs) with at least one positive lymph nodes, in comparison with EBV and high-risk HPVs-positive samples, which are low to intermediate grade IDCs, respectively. Future studies are needed to confirm the co-presence and the cooperation effect of these onco-viruses in human breast carcinogenesis and metastasis.

  15. Susceptibility of high-risk human papillomavirus type 16 to clinical disinfectants.

    PubMed

    Meyers, Jordan; Ryndock, Eric; Conway, Michael J; Meyers, Craig; Robison, Richard

    2014-06-01

    Little to nothing is known about human papillomavirus (HPV) susceptibility to disinfection. HPV is estimated to be among the most common sexually transmitted diseases in humans. HPV is also the causative agent of cervical cancers and other anogenital cancers and is responsible for a significant portion of oropharyngeal cancers. While sexual transmission is well documented, vertical and non-sexual transmission may also be important. Using recombinant HPV16 particles (quasivirions) and authentic HPV16 grown in three-dimensional organotypic human epithelial culture, we tested the susceptibility of high-risk HPV to clinical disinfectants. Infectious viral particles were incubated with 11 common clinical disinfectants, appropriate neutralizers were added to inactivate the disinfectant and solutions were filter centrifuged. Changes in the infectivity titres of the disinfectant-treated virus were measured compared with untreated virus. HPV16 is a highly resistant virus; more so than other non-enveloped viruses previously tested. The HPV16 quasivirions showed similar resistance to native virions, except for being susceptible to isopropanol, the triple phenolic and the lower concentration peracetic acid-silver (PAA-silver)-based disinfectant. Authentic virus and quasivirus were resistant to glutaraldehyde and ortho-phthalaldehyde and susceptible to hypochlorite and the higher concentration PAA-silver-based disinfectant. We present the first disinfectant susceptibility data on HPV16 native virions, which show that commonly used clinical disinfectants, including those used as sterilants in medical and dental healthcare facilities, have no effect on HPV16 infectivity. Policy changes concerning disinfectant use are needed. The unusually high resistance of HPV16 to disinfection supports other data suggesting the possibility of fomite or non-sexual transmission of HPV16. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial

  16. Susceptibility of high-risk human papillomavirus type 16 to clinical disinfectants

    PubMed Central

    Meyers, Jordan; Ryndock, Eric; Conway, Michael J.; Meyers, Craig; Robison, Richard

    2014-01-01

    Objectives Little to nothing is known about human papillomavirus (HPV) susceptibility to disinfection. HPV is estimated to be among the most common sexually transmitted diseases in humans. HPV is also the causative agent of cervical cancers and other anogenital cancers and is responsible for a significant portion of oropharyngeal cancers. While sexual transmission is well documented, vertical and non-sexual transmission may also be important. Methods Using recombinant HPV16 particles (quasivirions) and authentic HPV16 grown in three-dimensional organotypic human epithelial culture, we tested the susceptibility of high-risk HPV to clinical disinfectants. Infectious viral particles were incubated with 11 common clinical disinfectants, appropriate neutralizers were added to inactivate the disinfectant and solutions were filter centrifuged. Changes in the infectivity titres of the disinfectant-treated virus were measured compared with untreated virus. Results HPV16 is a highly resistant virus; more so than other non-enveloped viruses previously tested. The HPV16 quasivirions showed similar resistance to native virions, except for being susceptible to isopropanol, the triple phenolic and the lower concentration peracetic acid-silver (PAA-silver)-based disinfectant. Authentic virus and quasivirus were resistant to glutaraldehyde and ortho-phthalaldehyde and susceptible to hypochlorite and the higher concentration PAA-silver-based disinfectant. Conclusions We present the first disinfectant susceptibility data on HPV16 native virions, which show that commonly used clinical disinfectants, including those used as sterilants in medical and dental healthcare facilities, have no effect on HPV16 infectivity. Policy changes concerning disinfectant use are needed. The unusually high resistance of HPV16 to disinfection supports other data suggesting the possibility of fomite or non-sexual transmission of HPV16. PMID:24500190

  17. Prevalence and Genotyping of High Risk Human Papillomavirus in Cervical Cancer Samples from Punjab, Pakistan

    PubMed Central

    Siddiqa, Abida; Zainab, Maidah; Qadri, Ishtiaq; Bhatti, Muhammad Faraz; Parish, Joanna L.

    2014-01-01

    Cervical cancer is the third most common cause of cancer-related death in women worldwide. Infection with high-risk human papillomavirus (HPV) is established as the cause of cervical carcinoma, therefore, high risk HPV detection may have prognostic significance for the women who are at increased risk of disease progression. The paucity of data on the incidence of cervical cancer in Pakistan makes it difficult to determine disease burden. Even less information is available regarding the prevalent HPV strains in cervical specimens collected from this region. Cervical cancer is a neglected disease in Pakistan in terms of screening, prevention, and vaccination. Identification and accurate genotyping of the virus burden in cancer specimens is important to inform intervention policies for future management of HPV associated disease and to potentially stratify patients dependent on HPV status. In this study, detection and genotyping of HPV types 16 and 18 from 77 cervical specimens were carried out. Consensus primers GP5+/GP6+, which detect 44 genital HPV types, and type specific primers (TS16 and TS18) were used in conjunction with newly designed type specific primers. Using a combination of these methods of detection, a total of 94.81% (95% CI ±4.95) of cervical lesions were positive for HPV. Single infections of HPV16 were detected in 24.68% (95% CI ±9.63) of total samples and HPV18 was found in 25.97% (95% CI ±9.79) samples. Interestingly, a high proportion of samples (40.26%, 95% CI ±10.95) was positive for both HPV16 and 18, indicating a higher incidence of co-infection than previously reported for similar ethnic regions. The HPV genotype of 3.90% of HPV positive samples remained undetected, although these samples were positive with the GP5+/GP6+ primer set indicating infection with an HPV type other than 16 or 18. These data indicate that the overall incidence of high risk HPV infection in cervical cancer and intraepithelial neoplasia specimens in Punjab

  18. Prevalence and genotyping of high risk human papillomavirus in cervical cancer samples from Punjab, Pakistan.

    PubMed

    Siddiqa, Abida; Zainab, Maidah; Qadri, Ishtiaq; Bhatti, Muhammad Faraz; Parish, Joanna L

    2014-07-17

    Cervical cancer is the third most common cause of cancer-related death in women worldwide. Infection with high-risk human papillomavirus (HPV) is established as the cause of cervical carcinoma, therefore, high risk HPV detection may have prognostic significance for the women who are at increased risk of disease progression. The paucity of data on the incidence of cervical cancer in Pakistan makes it difficult to determine disease burden. Even less information is available regarding the prevalent HPV strains in cervical specimens collected from this region. Cervical cancer is a neglected disease in Pakistan in terms of screening, prevention, and vaccination. Identification and accurate genotyping of the virus burden in cancer specimens is important to inform intervention policies for future management of HPV associated disease and to potentially stratify patients dependent on HPV status. In this study, detection and genotyping of HPV types 16 and 18 from 77 cervical specimens were carried out. Consensus primers GP5+/GP6+, which detect 44 genital HPV types, and type specific primers (TS16 and TS18) were used in conjunction with newly designed type specific primers. Using a combination of these methods of detection, a total of 94.81% (95% CI ±4.95) of cervical lesions were positive for HPV. Single infections of HPV16 were detected in 24.68% (95% CI ±9.63) of total samples and HPV18 was found in 25.97% (95% CI ±9.79) samples. Interestingly, a high proportion of samples (40.26%, 95% CI ±10.95) was positive for both HPV16 and 18, indicating a higher incidence of co-infection than previously reported for similar ethnic regions. The HPV genotype of 3.90% of HPV positive samples remained undetected, although these samples were positive with the GP5+/GP6+ primer set indicating infection with an HPV type other than 16 or 18. These data indicate that the overall incidence of high risk HPV infection in cervical cancer and intraepithelial neoplasia specimens in Punjab

  19. Serological prevalence and persistence of high-risk human papillomavirus infection among women in Santiago, Chile

    PubMed Central

    2014-01-01

    Background Human papillomavirus (HPV) serology is a main factor for designing vaccination programs and surveillance strategies; nevertheless, there are few reports of HPV seroprevalence in the general population, especially in Latin America. This study aimed to describe high-risk HPV serological prevalence, persistence, and association with concurrent cervical infection, in Chilean women. Methods 1021 women from the general population, aged 15–85 years, were studied in 2001 of whom 600 were reexamined in 2006. The assessments at both time points included cervical HPV DNA testing, HPV antibody testing, cervical cytology and a sociodemographic/behavioral questionnaire. HPV DNA and antibodies against L1 protein of types 16, 18, 31, 33, 35, 45, 52, and 58 were assessed by reverse line blot and multiplex serology, respectively. Results Seropositivity was high at both baseline (43.2%) and follow-up (50.2%) and increased with age (p < 0.001); corresponding DNA prevalences were 6.7% and 8.7%. DNA and seroprevalence were associated at baseline (p = 0.01 for any HPV). Early age at first sexual intercourse and having had two or more sexual partners were independently associated with seropositivity. Most (82.0%) initially seropositive women remained seropositive at follow-up; 21.6% of initially seronegative women seroconverted, reaching 17.5% among women older than 60 years of age. ASCUS or worse cytology was correlated with HPV DNA positivity but not with HPV seropositivity. Conclusion HPV seroprevalence studies are a useful tool for learning about the dynamics of HPV infection in a community. This study contributes to understanding the natural history of HPV infection and provides a baseline assessment before the incorporation of HPV vaccination into a national program. PMID:24990706

  20. Histologic variation in high grade oral epithelial dysplasia when associated with high-risk human papillomavirus.

    PubMed

    Khanal, Sujita; Trainor, Patrick J; Zahin, Maryam; Ghim, Shin-Je; Joh, Joongho; Rai, Shesh N; Jenson, Alfred Bennett; Shumway, Brian S

    2017-05-01

    Reported cytologic alterations associated with high-risk human papillomavirus (HR-HPV) in oral epithelial dysplasia (HPV-OED) need further characterization. Archival cases of high-grade oral epithelial dysplasia (hgOED) (N = 38) were assigned a cytologic score (CS) based on the average number of mitotic, karyorrhectic, and apoptotic cells per high-power field. Three groups were then generated on the basis of increasing CS: Focal (group 1, N = 14), Intermediate (group 2, N = 12), and Diffuse (group 3, N = 12). Polymerase chain reaction-based HPV genotyping and p16 immunohistochemistry were performed. HR-HPV was found significantly more in group 3 (83.3%) compared with groups 1 and 2 (group 1&2; 42.9% and 41.7%, respectively; P = .047). HPV16 predominated in HR-HPV-positive cases (90.5%). By location, the tongue or the floor of mouth was associated with all groups (P = .04). Increasing CS was associated with a slightly younger age (P = .04) and increased expression of p16 (P = .005). CS and p16 expression were not sensitive but were highly specific predictors for HR-HPV presence. Based on limited follow-up information, HPV-OED does not differ in clinical aggressiveness compared with conventional OED. Increased CS in hgOED is strongly associated with HR-HPV (mostly HPV16) and p16 expression. CS and p16 expression are specific predictors of HR-HPV presence. Further molecular study and long-term follow-up of HPV-OED are needed. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

    PubMed

    Huh, Warner K; Ault, Kevin A; Chelmow, David; Davey, Diane D; Goulart, Robert A; Garcia, Francisco A R; Kinney, Walter K; Massad, L Stewart; Mayeaux, Edward J; Saslow, Debbie; Schiffman, Mark; Wentzensen, Nicolas; Lawson, Herschel W; Einstein, Mark H

    2015-02-01

    In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology or cotesting (cytology in combination with high-risk human papillomavirus [hrHPV] testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective U.S.-based registration study. Thirteen experts, including representatives from the Society of Gynecologic Oncology, the American Society for Colposcopy and Cervical Pathology, the American College of Obstetricians and Gynecologists, the American Cancer Society, the American Society of Cytopathology, the College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the U.S. Food and Drug Administration (FDA) for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for health care providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

  2. A Comparison of the Roche Cobas HPV Test With the Hybrid Capture 2 Test for the Detection of High-Risk Human Papillomavirus Genotypes.

    PubMed

    Levi, Angelique W; Bernstein, Jane I; Hui, Pei; Duch, Kara; Schofield, Kevin; Chhieng, David C

    2016-02-01

    All Food and Drug Administration-approved methods in the United States for human papillomavirus testing including the Hybrid Capture 2 human papillomavirus assay and the Roche cobas human papillomavirus test are approved for cytology specimens collected into ThinPrep media but not for specimens collected into SurePath solution. To compare the performance of the Roche cobas and Hybrid Capture 2 tests for the detection of high-risk human papillomavirus using both ThinPrep and SurePath preparations as part of a validation study. One thousand three hundred seventy-one liquid-based cytology samples, including 1122 SurePath and 249 ThinPrep specimens, were tested for high-risk human papillomavirus DNA using the Roche cobas human papillomavirus test and the Hybrid Capture 2 human papillomavirus assay. For cases with discrepant results, confirmatory testing was performed using Linear Array human papillomavirus testing. One hundred and fifty-six (11.38%) and 184 (13.42%) of the 1371 specimens tested positive for high-risk human papillomavirus DNA using the Hybrid Capture 2 human papillomavirus assay and Roche cobas human papillomavirus assay, respectively. In addition, 1289 (94.0%) of 1371 specimens demonstrated concordant high-risk human papillomavirus results with a κ value of 0.72 (95% confidence interval, 065-0.78). There was no statistically significant difference in the percentage of positive high-risk human papillomavirus results between the 2 liquid-based preparations with either assay. Discordant results between the 2 assays were noted in 82 of 1371 cases (6%). Twenty-seven of 82 cases (32.9%) were Hybrid Capture 2 positive/Roche cobas negative and 55 of 82 cases (67.1%) were Roche cobas positive/Hybrid Capture 2 negative. Two of 20 Hybrid Capture 2-positive/Roche cobas-negative cases (10%) and 26 of 37 Roche cobas-positive/Hybrid Capture 2-negative cases (70%) tested positive for high-risk human papillomavirus by Linear Array. Both assays showed good agreement

  3. Molecular genotyping of human papillomavirus l1 gene in low-risk and high-risk populations in Bangkok.

    PubMed

    Leaungwutiwong, Pornsawan; Bamrungsak, Busara; Jittmittraphap, Akanitt; Maneekan, Pannamas; Kosoltanapiwat, Nathamon; Kalambaheti, Thareerat; Kelley, James F

    2015-04-01

    Human papillomavirus (HPV) infections in Thailand are a public health concern, but information on HPV infection in sex workers and men who have sex with men (MSM) is limited. The aim of this study was to measure the prevalence and genotype distribution of HPV among low- and high-risk, HIV-negative populations. A total of 300 participants were categorized as general women, female sex workers, MSM, and MSM sex workers. Human papillomavirus infections were identified by the Papanicolaou test and nested polymerase chain reaction. A phylogenetic analysis of partial HPV L1 genes was performed. Abnormal cytology was found in 5% of general women, 10% of female sex workers, 24% of MSM, and 28% of MSM sex workers. Human papillomavirus was detected in 9% of general women, 13% of female sex workers, and 30% in both MSM and the MSM sex workers. The prevalence of HPV high-risk genotypes was significantly higher in female sex workers and MSM, whereas low-risk genotypes and genital warts were significantly higher in MSM sex workers. Significantly more patients with genital warts and cervical intraepithelial neoplasia I/anal intraepithelial neoplasia I harbored low-risk genotypes, whereas those with cervical intraepithelial neoplasia II/anal intraepithelial neoplasia II harbored high-risk genotypes. High- and low-risk HPV genotypes persist in high-risk groups in Bangkok. Some genotypes infecting at-risk populations are not vaccine preventable. These findings may help to elucidate the prevalence of HPV infections in Thailand and serve as the basis for additional investigations into risk factors for these populations.

  4. Prevalence of and Associated Risk Factors for High Risk Human Papillomavirus among Sexually Active Women, Swaziland.

    PubMed

    Ginindza, Themba G; Dlamini, Xolisile; Almonte, Maribel; Herrero, Rolando; Jolly, Pauline E; Tsoka-Gwegweni, Joyce M; Weiderpass, Elisabete; Broutet, Nathalie; Sartorius, Benn

    2017-01-01

    High risk human papillomavirus (hr-HPV) infection and the dual burden of HIV remains a huge challenge in some low-income countries (LICs) such as Swaziland with limited or no data. We estimated the prevalence and investigated determinants of hr-HPV, including HIV infection among sexually active women in Swaziland. A total of 655 women aged between 15 and 49 years from five health facilities were randomly enrolled using a cross-sectional study design. Cervical cells were tested for hr-HPV types using GeneXpert HPV Assays. The overall weighted hr-HPV prevalence was 46.2% (95%CI: 42.8-49.5). Of hr-HPV infected women, 12.4% (95%CI: 8.6-17.5) were HPV16-positive, 13.8% (95%CI:12.0-15.8) were positive for HPV18/45, 26.7% (95%CI: 24.2-29.3) for HPV31/33/35/52/58, 7.6% (95%CI: 7.6-11.9) for HPV51/59 and 11.0%, (95%CI: 7.9-15.3) for HPV39/56/66/68. Prevalence of hr-HPV decreased with increasing age. Overall HIV prevalence remained high (42.7%; 95%CI: 35.7-46.2). HIV infection was associated with hr-HPV infection (Adjusted OR = 4.9, 95%CI: 3.043-7.8, p<0.001). Overall hr-HPV/HIV co-infection was 24.4% (95%CI: 20.3-29.1) which was significantly higher among younger age groups (p<0.001). Prevalence of multiple group hr-HPV infection was significantly higher in HIV-positive versus -negative women (27.7% and 12.7% respectively, p<0.001). The presence, absence or unknown of history of STI with HIV did not appear to modify the relationship with hr-HPV (OR = 4.2, 95%CI: 2.6-7.1, OR = 4.6, 95%CI: 2.8-7.7, p<0.001, p<0.001 and OR = 4.1, 95%CI: 1.3-13.4, p<0.021 respectively). The prevalence of hr-HPV infection was high and significantly associated with HIV among sexually active women. Furthermore, the study has provided essential information about the HIV link with hr-HPV infections which may explain the high prevalence among HIV infected women. This can contribute to policy development and planning of prevention strategies incorporating HPV infection prevention especially among

  5. Prediction of High-Risk Types of Human Papillomaviruses Using Statistical Model of Protein “Sequence Space”

    PubMed Central

    Wang, Cong; Hai, Yabing; Liu, Xiaoqing; Liu, Nanfang; Yao, Yuhua; He, Pingan

    2015-01-01

    Discrimination of high-risk types of human papillomaviruses plays an important role in the diagnosis and remedy of cervical cancer. Recently, several computational methods have been proposed based on protein sequence-based and structure-based information, but the information of their related proteins has not been used until now. In this paper, we proposed using protein “sequence space” to explore this information and used it to predict high-risk types of HPVs. The proposed method was tested on 68 samples with known HPV types and 4 samples without HPV types and further compared with the available approaches. The results show that the proposed method achieved the best performance among all the evaluated methods with accuracy 95.59% and F1-score 90.91%, which indicates that protein “sequence space” could potentially be used to improve prediction of high-risk types of HPVs. PMID:25972913

  6. Prevalence of and Associated Risk Factors for High Risk Human Papillomavirus among Sexually Active Women, Swaziland

    PubMed Central

    Dlamini, Xolisile; Almonte, Maribel; Herrero, Rolando; Jolly, Pauline E.; Tsoka-Gwegweni, Joyce M.; Weiderpass, Elisabete; Broutet, Nathalie; Sartorius, Benn

    2017-01-01

    Background High risk human papillomavirus (hr-HPV) infection and the dual burden of HIV remains a huge challenge in some low-income countries (LICs) such as Swaziland with limited or no data. We estimated the prevalence and investigated determinants of hr-HPV, including HIV infection among sexually active women in Swaziland. Methods A total of 655 women aged between 15 and 49 years from five health facilities were randomly enrolled using a cross-sectional study design. Cervical cells were tested for hr-HPV types using GeneXpert HPV Assays. Results The overall weighted hr-HPV prevalence was 46.2% (95%CI: 42.8–49.5). Of hr-HPV infected women, 12.4% (95%CI: 8.6–17.5) were HPV16-positive, 13.8% (95%CI:12.0–15.8) were positive for HPV18/45, 26.7% (95%CI: 24.2–29.3) for HPV31/33/35/52/58, 7.6% (95%CI: 7.6–11.9) for HPV51/59 and 11.0%, (95%CI: 7.9–15.3) for HPV39/56/66/68. Prevalence of hr-HPV decreased with increasing age. Overall HIV prevalence remained high (42.7%; 95%CI: 35.7–46.2). HIV infection was associated with hr-HPV infection (Adjusted OR = 4.9, 95%CI: 3.043–7.8, p<0.001). Overall hr-HPV/HIV co-infection was 24.4% (95%CI: 20.3–29.1) which was significantly higher among younger age groups (p<0.001). Prevalence of multiple group hr-HPV infection was significantly higher in HIV-positive versus -negative women (27.7% and 12.7% respectively, p<0.001). The presence, absence or unknown of history of STI with HIV did not appear to modify the relationship with hr-HPV (OR = 4.2, 95%CI: 2.6–7.1, OR = 4.6, 95%CI: 2.8–7.7, p<0.001, p<0.001 and OR = 4.1, 95%CI: 1.3–13.4, p<0.021 respectively). Conclusion The prevalence of hr-HPV infection was high and significantly associated with HIV among sexually active women. Furthermore, the study has provided essential information about the HIV link with hr-HPV infections which may explain the high prevalence among HIV infected women. This can contribute to policy development and planning of prevention

  7. p16 - a Possible Surrogate Marker for High-Risk Human Papillomaviruses in Oral Cancer?

    PubMed

    Sritippho, Thanun; Pongsiriwet, Surawut; Lertprasertsuke, Nirush; Buddhachat, Kittisak; Sastraruji, Thanapat; Iamaroon, Anak

    2016-01-01

    High-risk human papillomaviruses (HR-HPV), particularly types 16 and 18, have been found to play an important role in head and neck cancer, including oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). p16, a cell cycle inhibitor, has been postulated as a surrogate marker for HR-HPV, since p16 is aberrantly overexpressed in such lesions, especially in HR-HPV-positive OPSCC. However, p16 as a surrogate marker for HR-HPV infection in cancers of the oral cavity remains controversial. The objectives of the study were to investigate the expression of p16 and the presence of HR-HPV in OSCC and oral verrucous carcinoma (VC) and to determine if p16 could be used as a surrogate marker for HR-HPV. Forty one formalin-fixed, paraffin-embedded tissues of OSCC (n=37) or VC (n=4) with clinical and histopathologic data of each case were collected. Expression of p16 was determined by immunohistochemistry, focusing on both staining intensity and numbers of positive cells. The presence of HPV types 16 and 18 was detected by polymerase chain reaction (PCR). Descriptive statistics were employed to describe the demographic, clinical, and histopathologic parameters. Associations between p16 overexpression, HR-HPV and all variables were determined by Fisher's exact test, odds ratios (ORs) and corresponding 95% confidence intervals (CIs). In addition, the use of p16 as a surrogate marker for HR-HPV was analyzed by sensitivity and specificity tests. p16 was overexpressed in 8/37 cases (21.6%) of OSCC and 2/4 cases (50%) of VC. HPV-16 was detected in 4/34 OSCC cases (11.8%) and HPV-18 was detected in 1/34 OSCC cases (2.9%). Co-infection of HPV-16/18 was detected in 1/4 VC cases (25%). Both p16 overexpression and HR-HPV were significantly associated with young patients with both OSCC and VC (<0.05, OR 20, 95% CI 1.9-211.8; <0.05, OR 23.3, 95% CI 2.4-229.7, respectively). p16 was able to predict the presence of HPV-16/18 in OSCC with 40% sensitivity and 79

  8. High-risk human papillomavirus in HIV-infected women undergoing cervical cancer screening in Lilongwe, Malawi: A pilot study

    PubMed Central

    Reddy, Deepa; Njala, Joseph; Stocker, Penny; Schooley, Alan; Flores, Martiniano; Tseng, Chi-Hong; Pfaff, Colin; Jansen, Perry; Mitsuyasu, Ronald T.; Hoffman, Risa M.

    2015-01-01

    Introduction Rates of abnormal visual inspection with acetic acid (VIA) and prevalence of high-risk human papillomavirus (HPV) subtypes have not been well characterized in HIV-infected women in Malawi. Methods We performed a prospective cohort study of VIA (N=440) in HIV-infected women ages 25-59, with a nested study of HPV subtypes in first 300 women enrolled. Wilcoxon's Rank-Sum Test was used to compare continuous variables and Fisher's exact test was used to compare categorical variables between women with normal versus abnormal VIA. Results: Of 440 women screened, 9.5% (N=42) had abnormal VIA with 69.0% (N=29) having advanced disease not amenable to cryotherapy. Of 294 women with HPV results, 39% (N=114) of women were positive for high-risk HPV infection. Only lower CD4 count (287 cells/mm3 vs. 339 cells/mm3, p=0.03) and high-risk HPV (66.7% versus 35.6%, p<0.01) were associated with abnormal VIA. The most common high-risk HPV subtypes in women with abnormal VIA were 35 (33.3%), 16 (26.7%), and 58 (23.3%). Conclusion Low CD4 cell count was associated with abnormal VIA and raises the importance of early ART and expanded availability of VIA. HPV vaccines targeting additional non-16/18 high-risk HPV subtypes may have greater protective advantages in countries such as Malawi. PMID:24928579

  9. Prevalence of high-risk human papillomavirus types 16 and 18 in healthy women with cytologically negative pap smear in Iran.

    PubMed

    Safaei, Akbar; Khanlari, Mahsa; Momtahen, Moghdeh; Monabati, Ahmad; Robati, Minoo; Amooei, Sedigheh; Valibeigi, Behnaz; Azarpira, Negar

    2010-01-01

    Because human papillomavirus (HPV) is one of the causal factors in cervical cancer, understanding the epidemiology of this infection is an important step towards developing strategies for prevention. We evaluated the prevalence of high-risk human papillomavirus Types 16 and 18 in cervical samples from 402 healthy women with normal Pap smears by testing with type-specific primers in the polymerase chain reaction. Participants were seen at two gynecological clinics affiliated to the Shiraz University of Medical Sciences in Iran. The prevalence of positive HPV findings was 5.5%; high-risk HPV human papillomavirus Type 16 prevalence was 2% and no patient harbored HPV-18. The prevalence of HPV was 4.5% in younger age group and gradually increased to 20% in the 4 th decade. The prevalence of high-risk HPV was highest in the youngest women and gradually decreased with age. Overall, the prevalence of HPV in our population is low.

  10. Reduced expression of autophagy markers correlates with high-risk human papillomavirus infection in human cervical squamous cell carcinoma

    PubMed Central

    WANG, HUA-YI; YANG, GUI-FANG; HUANG, YAN-HUA; HUANG, QI-WEN; GAO, JUN; ZHAO, XIAN-DA; HUANG, LI-MING; CHEN, HONG-LEI

    2014-01-01

    Infection by an oncogenic human papillomavirus (HPV), in particular HPV16 and 18, is a high risk factor for developing cervical cancer; however, viral infection alone is not sufficient for cancer progression. Autophagy is hypothesized to be an important process during carcinogenesis. The aim of the present study was to investigate the association between autophagy and high-risk HPV (hrHPV) infection in human cervical squamous cell carcinomas (SCCs), and to analyze the clinical significance of this association. Quantum dot (QD)-based immunofluorescence histochemistry was used to detect the expression of autophagy markers, Beclin-1 and microtubule-associated proteins 1A/1B light chain 3B (LC3B) proteins, in 104 cases of cervical cancer (including 80 SCCs and 24 adenocarcinomas) and 20 normal cervical tissues. hrHPV (HPV16/18) infection was detected by QDs based fluorescence in situ hybridization in cervical cancers. The results revealed that the expression levels of Beclin-1 and LC3B were significantly lower in cervical cancer cells when compared with those of normal cervical squamous epithelial cells, and were found to negatively correlate with hrHPV infection. The expression levels of Beclin-1 and LC3B were not associated with age, tumor grade, tumor stage, tumor node metastasis stage or lymph node metastasis. However, a positive correlation was identified between Beclin-1 and LC3B protein expression. In addition, the absence of autophagy in combination with hrHPV infection may accelerate the progression of cervical SCC. In conclusion, decreased expression of Beclin-1 and LC3B may be important in cervical carcinogenesis. The hrHPV-host cell interaction may inhibit autophagy, which may aid virus duplication and infection, as well as cervical cancer development. PMID:25202355

  11. High prevalence of high risk human papillomavirus-capsid antibodies in human immunodeficiency virus-seropositive men: a serological study.

    PubMed

    Höpfl, Reinhard; Petter, Anton; Thaler, Petra; Sarcletti, Mario; Widschwendter, Andreas; Zangerle, Robert

    2003-04-30

    Serological study of human papillomavirus (HPV)-antibodies in order to estimate the HPV-prevalence as risk factor for the development of HPV-associated malignancies in human immunodeficiency virus (HIV)-positive men. Sera from 168 HIV-positive men and 330 HIV-negative individuals (including 198 controls) were tested using a direct HPV-ELISA specific to HPV-6, -11, -16, -18, -31 and bovine PV-1 L1-virus-like particles. Serological results were correlated with the presence of HPV-associated lesions, the history of other sexually transmitted diseases (STD) and HIV classification groups. In HIV-negative men low risk HPV-antibodies were prevailing and associated with condylomatous warts (25.4%). Strikingly, HIV-positive men were more likely to have antibodies to the high-risk HPV types -16, -18, -31, and low risk antibodies were not increased in a comparable range. Even those HIV-positive heterosexual individuals without any HPV-associated lesions exhibited preferentially antibody responses to the oncogenic HPV-types (cumulative 31.1%). The highest antibody detection rate (88,8%) was observed within the subgroup of nine HIV-positive homosexual men with anogenital warts. Three HIV-positive patients had HPV-associated carcinomas, in all of them HPV-16 antibodies were detected. Drug use and mean CD4-cell counts on the day of serologic testing had no influence on HPV-IgG antibody prevalence, as had prior antiretroviral therapy or clinical category of HIV-disease. High risk HPV-antibodies in HIV-infected and homosexual men suggest a continuous exposure to HPV-proteins throughout the course of their HIV infection, reflecting the known increased risk for anogenital malignancies in these populations. The extensive increase of high risk antibodies (compared to low risk antibodies) in HIV-positive patients cannot be explained by differences in exposure history alone, but suggests defects of the immunological control of oncogenic HPV-types. HPV-serology is economic and can detect

  12. Oropharyngeal and laryngeal but not oral cancers are strongly associated with high-risk human papillomavirus in 172 Greek patients.

    PubMed

    Tsimplaki, Elpida; Argyri, Elena; Sakellaridis, Athanassios; Kyrodimos, Efthimios; Xesfyngi, Dimitra; Panotopoulou, Efstathia

    2017-01-01

    A strong and consistent association has been reported between human papillomavirus (HPV) infection and oropharyngeal cancer, whereas a similar link has not yet been clarified in oral and laryngeal cancer. The purpose of this study was to investigate the association between HPV infection and head and neck squamous cell carcinoma (HNSCC) in Greek patients. Cytological or tissue specimens from 172 cases patients with HNSCC and cytological specimens from 91 control subjects were analyzed for HPV DNA detection and genotyping using a microarray-based assay. Multivariate logistic regression was used to estimate odds ratios (ORs) for the association between the presence of HPV infection and HNSCC for each of the tumor site, after adjustment for potential confounders. The adjusted ORs for positivity to high-risk HPV infection for oropharyngeal and laryngeal cancer were 20.3 (95% CI: 1.7-250.1) and 22.8 (95% CI: 2.5-206.2), respectively. High-risk HPV infection was not significantly associated with oral cancer. HPV infection was independently associated with poorly differentiated tumors (OR = 2.8; 95% CI: 1.1-7.5). Our results suggest a strong association of high-risk HPV infection with oropharyngeal and laryngeal cancer. J. Med. Virol. 89:170-176, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Natural history of human papillomavirus infection in non-vaccinated young males: low clearance probability in high-risk genotypes.

    PubMed

    Cai, T; Perletti, G; Meacci, F; Magri, V; Verze, P; Palmieri, A; Mazzoli, S; Santi, R; Nesi, G; Mirone, V; Bartoletti, R

    2016-03-01

    In this study, we aimed to investigate the clearance of type-specific genital human papillomavirus (HPV) infection in heterosexual, non-HPV-vaccinated males whose female partners were positive to HPV DNA tests. All consecutive men attending the same sexually transmitted diseases (STD) centre between January 2005 and December 2006 were considered for this study. All subjects (n = 1009) underwent a urologic visit and microbiological tests on first void, midstream urine and total ejaculate samples. One hundred and five patients were positive for HPV DNA (10.4 %; mean age: 34.8 ± 5.8 years) and consented to clinical examination and molecular diagnostic assays for HPV detection scheduled every 6 months (median surveillance period of 53.2 months). HPV genotypes were classified as high risk, probable high risk and low risk. HPV-positive samples which did not hybridise with any of the type-specific probes were referred to as positive non-genotypeable. At enrollment, the distribution of HPV genotypes was as follows: high-risk HPV (n = 37), probable high-risk HPV (n = 6), low-risk HPV (n = 23) and non-genotypeable HPV (n = 39). A high HPV genotype concordance between stable sexual partners emerged (kappa = 0.92; p < 0.001). At the end of the study, 71/105 (67.6 %) subjects were negative for HPV (mean virus clearance time: 24.3 months). With regard to the HPV genotype, virus clearance was observed in 14/37 (37.8 %) high-risk HPV cases, 6/6 (100 %) probable high-risk HPV cases, 20/23 (86.9 %) low-risk HPV cases and 31/39 (79.5 %) non-genotypeable cases. The high-risk HPV genotypes showed the lowest rate and probability of viral clearance (p < 0.001). In our series, high-risk HPV infections were more likely to persist over time when compared with other HPV genotypes.

  14. High risk human papillomavirus genotyping in clinical samples: evaluation of different commercial tests.

    PubMed

    Paolini, F; Rollo, F; Brandi, R; Benevolo, M; Mariani, L; Cercato, M C; Vocaturo, A; Venuti, A

    2011-01-01

    The aim of the present study is to compare the performance of several commercial human papillomavirus (HPV) tests in a cohort of 281 women. The hybrid capture II, the PreTect-HPV-Proofer, the linear array, and DR.HPVTMIVD were utilized to detect and type HPV in parallel with in-house PCR tests followed by direct automated sequencing or by sub-cloning and sequencing. The concordance levels along with other tests were evaluated with a Cohen's K value varying between 0.60 to 0.88, indicating good correlation with nearly perfect agreement between hybrid capture II, (HCII) and the linear array test. High sensitivity was recorded by the linear array and HCII with 100% (95% CI, 0.8021 to 1.0000) detection of cervical intraepithelial neoplasia (CIN) III by both methods. Conversely, the PreTect-HPV-Proofer showed high specificity with 12% (95% CI, 0.7966 to 0.9163) positivity on normal samples. The genotyping analysis showed that agreement among tests was only low to moderate with great differences between different HPV types. Multiple infections were detected with poor concordance and sub-cloning assays revealed the presence of a lower number of HPV in comparison to the other methods. In summary, the use of different HPV tests applied to the same group of cervical smears may possibly lead to incongruent results, suggesting the need to standardize type-specific sensitivity of genotyping methods and the need to evaluate their accuracy in detecting multiple HPV infections. This would be a prerequisite for the use of genotyping assays in cervical cancer screening programs.

  15. Antibodies against high-risk human papillomavirus proteins as markers for invasive cervical cancer.

    PubMed

    Combes, Jean-Damien; Pawlita, Michael; Waterboer, Tim; Hammouda, Doudja; Rajkumar, Thangarajan; Vanhems, Philippe; Snijders, Peter; Herrero, Rolando; Franceschi, Silvia; Clifford, Gary

    2014-11-15

    Different human papillomavirus (HPV) genes are expressed during the various phases of the HPV life cycle and may elicit immune responses in the process towards malignancy. To evaluate their association with cervical cancer, antibodies against proteins from HPV16 (L1, E1, E2, E4, E6 and E7) and HPV18/31/33/35/45/52/58 (L1, E6 and E7) were measured in serum of 307 invasive cervical cancer cases and 327 controls from Algeria and India. Antibody response was evaluated using a glutathione S-transferase-based multiplex serology assay and HPV DNA detected from exfoliated cervical cells using a GP5+/6+-mediated PCR assay. Among HPV16 DNA-positive cases, seroprevalence of HPV16 antibodies ranged from 16% for HPV16 E1 to 50% for HPV16 E6 and all were significantly higher than controls. Seroprevalence of E6, E7 and L1 antibodies for HPV18 and for at least one of HPV31/33/35/45/52/58 were also higher in cases positive for DNA of the corresponding type (50% and 30% for E6 of HPV18 and HPV31/33/35/45/52/58 combined, respectively). E6 and E7 antibodies were rarely found in controls, but cross-reactivity was evident among cancer cases positive for DNA of closely phylogenetically-related HPV types. E6 or E7 antibodies against any of the eight HPV types were detected in 66.1% of all cervical cancer cases, as compared to 10.1% of controls. E6, and to a lesser extent E7, antibodies appear to be specific markers of HPV-related malignancy. However, even among cases positive for the same type of HPV DNA, approximately one-third of cervical cancer cases show no detectable immune response to either E6 or E7.

  16. The prevalence and significance of high-risk human papillomavirus DNA test in southern Malaysia and Singapore.

    PubMed

    Tay, Sun-Kuie; Tay, Yeng-Kwang

    2009-06-01

    To investigate the prevalence of high-risk human papillomavirus (HPV) and its associated cytological abnormalities among women attending cervical screening clinics in southern Malaysia and Singapore. Laboratory results of Hybrid Capture-II (Digene) HPV DNA and liquid-based cytology tests of consecutive women who had screening performed between January 2004 and December 2006 were studied retrospectively. Of 2364 women studied, the overall prevalence of high-risk HPV DNA detection rate was 25.6%. The prevalence peaked at 49.1% for women between 20 and 24 years old and declined to 23% among women between the age of 30 and 49 years. A small second peak of prevalence rate of 30% was observed among women above the age of 50 years old. 76.1% of the high-risk HPV infection regressed within the study period. An incidence infection rate of 16% was noted among a small group of women who had a second HPV DNA test. A total of 1153 women had both the HPV DNA and the cytology tests. Cytological abnormality (ASCUS or more) was detected in 8.9% in HPV DNA-positive group and in 3.1% in HPV DNA-negative group (P < 0.001). The risk ratio for HSIL was 9.8 for HPV-positive women compared to HPV-negative women. The prevalence of cytological abnormalities increased with increasing age of the women. The epidemiology and clinical impact of high-risk HPV infection for women in Southern Malaysia and Singapore were indistinguishable from experience elsewhere. The apparent moderately high incidence of cervical cancer was explainable by suboptimal screening program.

  17. Comparison of Human Papillomavirus Detection in Urine and Cervical Samples Using High-Risk HPV DNA Testing in Northern Thailand

    PubMed Central

    Settakorn, Jongkolnee; Sukpan, Kornkanok; Lekawanvijit, Suree; Katruang, Narisara; Siriaunkgul, Sumalee

    2016-01-01

    Objective. To evaluate the performance of high-risk human papillomavirus (HPV) DNA testing in urine samples compared to that of cervical sample testing in Northern Thailand. Methods. Paired urine and cervical samples were collected during the follow-up of women with a previous positive HPV test. HPV testing was performed using the Cobas 4800 HPV Test. Linear Array assay was used for genotyping in selected cases. Results. Paired urine and cervical samples were obtained from 168 women. Of 123 paired samples with valid results, agreement in the detection of high-risk HPV DNA was present in 106 cases (86.2%), with a kappa statistic of 0.65 (substantial agreement). Using the cervical HPV results as a reference, the sensitivity of urine HPV testing was 68.6% (24/35) and the specificity 93.2% (82/88). For the detection of histologic high-grade squamous intraepithelial lesion or worse (HSIL+), the sensitivity of urine HPV testing was 80.0% (4/5) and the specificity 78.0% (92/118). Conclusion. Although urine HPV testing had a rather low sensitivity for HPV detection, its sensitivity for histologic HSIL+ detection was high. For clinical use of urine HPV testing, standardization of specimen collection and processing techniques or application of a more sensitive test, especially in the detection of HPV52 and HPV58, is necessary. PMID:28101107

  18. Requirement of epidermal growth factor receptor for hyperplasia induced by E5, a high-risk human papillomavirus oncogene.

    PubMed

    Genther Williams, Sybil M; Disbrow, Gary L; Schlegel, Richard; Lee, Daekee; Threadgill, David W; Lambert, Paul F

    2005-08-01

    Multicellular organisms rely on complex networks of signaling cascades for development, homeostasis, and responses to the environment. These networks involve diffusible signaling molecules, their receptors, and a variety of downstream effectors. Alterations in the expression or function of any one of these factors can contribute to disease, including cancer. Many viruses have been implicated in cancer, and some of these modulate cellular signal transduction cascades to carry out their life cycles. High-risk human papillomaviruses (HPVs), the causative agents of most cervical and anogenital cancers, encode three oncogenes. One of these, E5, has been postulated to transform cells in tissue culture by modulating growth factor receptors. In this study, we generate and characterize transgenic mice in which the E5 gene of the most common high-risk HPV, HPV16, is targeted to the basal layer of the stratified squamous epithelium. In these mice, E5 alters the growth and differentiation of stratified epithelia and induces epithelial tumors at a high frequency. Through the analysis of these mice, we show a requirement of the epidermal growth factor receptor for the hyperplastic properties of E5.

  19. Prevalence of High risk Human Papillomavirus in cervical dysplasia and cancer samples from twin cities in Pakistan.

    PubMed

    Gul, Sana; Murad, Sheeba; Javed, Aneela

    2015-05-01

    Human Papilloma Virus (HPV) is small DNA virus mostly infecting mucosa and cutaneous keratinocytes. So far, more than 200 Human papillomaviruses are known. HPV have been divided into high- and low-risk on the basis of their oncogenic potential. High risk HPV is considered to be the main etiological cause for cervical cancer. The current study was designed to screen the local cervical cancer patients from the twin cities of Pakistan for the occurance of high risk HPV. A total of 67 formalin fixed paraffin-embedded samples of cervical cancer biopsies were obtained from the government hospitals in Islamabad and Rawalpindi. Cervical cancer biopsies were examined for the presence of HPV DNA. Polymerase chain reaction (PCR) was used for the amplification of a region in the HPV-L1 gene for the general detection of the Papilloma virus and for the genotype specific detection of high risk HPV 16 and 18 using the GP5/GP6 primers and genotype specific primers, respectively. HPV DNA was detected in 59 out of 67 samples analyzed. 30 samples showed the presence of HPV16 while 22 samples were positive for HPV18. HPV subtype could not be determined in 7 samples. Our results show a strong association between HPV infection and cervical cancer among women in twin cities of Pakistan. One way to minimize the disease burden in relation to HPV infection in Pakistani population is the use of prophylactic vaccines and routine screening. An early diagnosis of HPV infection will allow better health management to reduce the risk of developing cervical cancer. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Prevalence of human papillomavirus infection of the anal canal in women: A prospective analysis of high-risk populations

    PubMed Central

    Kost, Bernd P.; Hofmann, Jörg; Stoellnberger, Susanne; Bergauer, Florian; Blankenstein, Thomas; Alba-Alejandre, Irene; Stein, Angela; Stuckart, Claudia; Weizsäcker, Katharina; Mylonas, Ioannis; Mahner, Sven; Gingelmaier, Andrea

    2017-01-01

    Infection with certain types of human papillomavirus (HPV) has been associated with the development of cervical and anal cancer. Worldwide, the incidence of anal cancer has increased markedly. The present study aimed to evaluate the prevalence of HPV infection of the uterine cervix and anal canal in human immunodeficiency virus (HIV)- and non-HIV-infected risk populations. Cervical and anal HPV swabs and cytology samples were collected from 287 patients at the University Hospital of Munich, Germany between 2011 and 2013. Patients were divided into HIV-negative controls (G1) and two risk groups, including HIV-negative patients with cytological abnormalities of the cervix (G2) and HIV-infected patients (G3). Data, including clinical parameters, were analysed. The risk groups had significantly more positive results for HPV in the anus (71.03 and 83.15% for G2 and G3, respectively), as compared with G1. The predominant HPV genotypes found in the anus were high-risk HPV genotypes, which were significantly correlated with concomittant cervical HPV findings. In the risk groups, a significant association between the cytological findings and HPV detection in the cervix was found, while the results of the anus revealed no significance. The results of the present study suggested that the prevalence of HPV infection in the anal canal of risk populations is high. Furthermore, patients with abnormal cervical cytology results and HIV-infected women, irrespective of their individual cervical findings, may have a risk of concomittant anal high-risk HPV infection. Based on the predominant HPV genotypes found in the study, HPV vaccination could reduce the incidence of anal cancer. Nevertheless, high-risk patients should be intensively screened for anal squamous intraepithelial abnormalities to avoid invasive cancer stages. PMID:28454426

  1. Prevalence of human papillomavirus infection of the anal canal in women: A prospective analysis of high-risk populations.

    PubMed

    Kost, Bernd P; Hofmann, Jörg; Stoellnberger, Susanne; Bergauer, Florian; Blankenstein, Thomas; Alba-Alejandre, Irene; Stein, Angela; Stuckart, Claudia; Weizsäcker, Katharina; Mylonas, Ioannis; Mahner, Sven; Gingelmaier, Andrea

    2017-04-01

    Infection with certain types of human papillomavirus (HPV) has been associated with the development of cervical and anal cancer. Worldwide, the incidence of anal cancer has increased markedly. The present study aimed to evaluate the prevalence of HPV infection of the uterine cervix and anal canal in human immunodeficiency virus (HIV)- and non-HIV-infected risk populations. Cervical and anal HPV swabs and cytology samples were collected from 287 patients at the University Hospital of Munich, Germany between 2011 and 2013. Patients were divided into HIV-negative controls (G1) and two risk groups, including HIV-negative patients with cytological abnormalities of the cervix (G2) and HIV-infected patients (G3). Data, including clinical parameters, were analysed. The risk groups had significantly more positive results for HPV in the anus (71.03 and 83.15% for G2 and G3, respectively), as compared with G1. The predominant HPV genotypes found in the anus were high-risk HPV genotypes, which were significantly correlated with concomittant cervical HPV findings. In the risk groups, a significant association between the cytological findings and HPV detection in the cervix was found, while the results of the anus revealed no significance. The results of the present study suggested that the prevalence of HPV infection in the anal canal of risk populations is high. Furthermore, patients with abnormal cervical cytology results and HIV-infected women, irrespective of their individual cervical findings, may have a risk of concomittant anal high-risk HPV infection. Based on the predominant HPV genotypes found in the study, HPV vaccination could reduce the incidence of anal cancer. Nevertheless, high-risk patients should be intensively screened for anal squamous intraepithelial abnormalities to avoid invasive cancer stages.

  2. Prevalence of high-risk human papillomavirus in an inner-city population with atypical squamous cells of undetermined significance.

    PubMed

    Allen, Gretchen L; Klobocista, Merieme M; Sugarman, Shannon; Gravel, Katie; Feldman, Deborah; Schnatz, Peter F

    2009-04-01

    To compare the prevalence of high-risk human papillomavirus (HPV) in patients with atypical squamous cells of undetermined significance (ASCUS) cytology in an inner-city clinic and a private office population to determine if HPV screening is useful in either group before colposcopy. After an institutional review board approval at Hartford Hospital, we reviewed the charts of patients with ASCUS cytology and high-risk HPV DNA who were seen at the Community Health Services, Inc. in Hartford, CT (clinic patients), between January 1, 2000, and July 1, 2004, and at a private practice site in Hartford, CT (private patients), between January 1, 2004, and December 31, 2004. All charts were reviewed for demographic information, history of sexually transmitted diseases, tobacco, alcohol, and other drug use. A power analysis indicated that 32 patients would be needed in each group for a p <.05 with 80% confidence. A total of 257 patient's charts were reviewed: 79 clinic charts and 178 private office charts. Three patients were eliminated due to a lack of HPV testing. High-risk HPV was identified in 94.9% of the clinic patients and 45.5% of the private patients. The populations were statistically different with regard to history of chlamydia (26.6% of clinic patients and 6.2% of private office patients; p <.0001), gonorrhea (11.4% clinic patients and 1.1% of private patients; p =.0005), and trichomonas (7.6% of clinic patients and 0% of private office patients; p =.0007). The prevalence of herpes simplex virus in clinic patients was 2.5%, whereas it was present in 6.2% of private patients (p =.35). Tobacco use was significantly higher in clinic patients (31.6% of clinic patients and 15.2% of private patients; p =.009). In our study, 94.9% of the women in the clinic population with an ASCUS cytology had high-risk HPV compared with a rate of 45.5% in the private patients studied. Because most clinic patients with ASCUS have high-risk HPV, it is reasonable to defer reflex testing

  3. HLA-DP is the cervical cancer susceptibility loci among women infected by high-risk human papillomavirus: potential implication for triage of human papillomavirus-positive women.

    PubMed

    Jia, Meiqun; Han, Jing; Hang, Dong; Jiang, Jie; Wang, Minjie; Wei, Baojun; Dai, Juncheng; Zhang, Kai; Guo, Lanwei; Qi, Jun; Ma, Hongxia; Shi, Jufang; Ren, Jiansong; Hu, Zhibin; Dai, Min; Li, Ni

    2016-06-01

    Given that only a small proportion of women infected by high-risk human papillomavirus (hrHPV) develop cervical cancer, it's important to identify biomarkers for distinguishing women with hrHPV positivity who might develop cervical cancer from the transient infections. In this study, we hypothesized that human leukocyte antigens (HLA) susceptibility alleles might contribute to cervical cancer risk among females infected by hrHPV, and interact with hrHPV types. A case-control study with 593 cervical cancer cases and 407 controls (all hrHPV positive) was conducted to evaluate the effect of eight HLA-related single-nucleotide polymorphisms (SNPs) and their interactions with hrHPV types on the risk of cervical cancer. Three HLA-DP SNPs (rs4282438, rs3117027, and rs3077) were found to be significantly associated with risk of cervical cancer (rs4282438: odds ratio (OR) = 0.72, 95 % confidence interval (CI) = 0.56-0.93; rs3117027: OR = 1.41, 95 % CI = 1.10-1.83; and rs3077: OR = 1.37, 95 % CI = 1.04-1.80) among women infected with hrHPV. An additive interaction between HPV16 and rs4282438 for cervical cancer risk was also found (P for interaction = 0.002). Compared with subjects carrying variant genotypes (GG/TG) and non-HPV16 infections, those carrying wild-type genotype (TT) of rs4282438 and HPV16 positive had a 5.22-fold increased risk of cervical cancer (95 % CI = 3.39-8.04). Our study supported that certain HLA-DP alleles in concert with HPV16 could have a predisposition for cervical cancer development, which may be translated for triage of hrHPV-positive women.

  4. Detection of human papillomavirus DNA in gastric carcinoma specimens in a high-risk region of Iran

    PubMed Central

    Fakhraei, Farzaneh; Haghshenas, Mohammad Reza; Hosseini, Vahid; Rafiei, Alireza; Naghshvar, Farshad; Alizadeh-Navaei, Reza

    2016-01-01

    Gastric cancer is the fourth most common type of cancer worldwide and is associated with high mortality rates. The incidence of gastric cancer varies widely in different geographical regions. For example, in Iran, the most northern and northwestern regions are considered to be high-risk areas for gastric cancer. The aim of the present study was to determine the distribution of human papillomavirus (HPV) genotypes among patients with gastric carcinoma in Mazandaran province, Northern Iran, which is a high-risk area. A total of 100 paraffin-embedded tissue samples were obtained from 70 males and 30 females with gastric carcinoma, diagnosed between 2006 and 2013, in the Imam Khomeini Hospital (Sari, Iran). GP5+/GP6+ general primers were applied for detection of HPV DNA in the specimens. Positive samples were then selected and high-risk HPV genotyping was performed. The samples were analyzed by polymerase chain reaction and five (5%) samples were identified to be positive for HPV DNA [four male (5.7%) and one female (3.3%)]. Three (60%) samples were positive for HPV-16, one (20%) sample was positive for HPV-18 and one (20%) sample was positive for HPV-45. Following pathological diagnosis, 88 samples were identified as gastric adenocarcinoma, nine samples were gastric lymphoma, and three samples were gastric and esophagus adenocarcinoma. According to the findings of the present study and the rate of HPV infection in patients with gastric carcinoma, an association between HPV infection and gastric carcinoma in subjects from Northern Iran was not identified. PMID:27588180

  5. Impact of Possibly Oncogenic High-Risk Human Papillomavirus (HPV) Types in Triage for ASC-US Cervical Cytology Results.

    PubMed

    Amarosa, Emily J; Winer, Rachel L; Hong, Karen J; Mao, Constance

    2015-10-01

    Current guidelines recommend including 13 or 14 high-risk human papillomavirus (HPV) types for triage of atypical squamous cells of undetermined significance (ASC-US) cervical cytology; however, at least 13 additional types are considered possibly oncogenic. We evaluated the effect of including possibly oncogenic HPV types in the test panel. Outcomes for all women 30 years or older with ASC-US and positive HPV testing who underwent colposcopic biopsy at University of Washington Medical Center-affiliated clinics between 2010 and 2011 were reviewed. We compared biopsy results between cases that were HPV positive for 1 or more of 13 possibly oncogenic types only (26/53/55/62/64/67/69/71/73/82/83/84/IS39) versus 1 or more of the 14 established high-risk types (16/18/31/33/35/39/45/51/52/56/58/59/66/68). We used the Fisher exact test to compare cervical intraepithelial neoplasia grade 2 or higher (CIN2+) diagnoses between HPV risk groups. Three hundred twenty-six ASC-US HPV-positive cervical cytology results were identified, with 170 that were linked to subsequent cervical biopsy results. Among 51 cases positive for possibly oncogenic types only, 31 (61%) had no neoplasia, 20 (39%) had CIN1, and none had CIN2+. Among 119 controls positive for at least one established high-risk type, 64 (53%) had no neoplasia, 42 (35%) had CIN1, and 13 (11%) had CIN2+ (p = .01 for the comparison of CIN2+ diagnoses between groups). The inclusion of possibly oncogenic types in the HPV test panel led to an additional 51 colposcopy biopsies (33% increase), with no additional cases of CIN 2+. Our results suggest that including possibly oncogenic HPV types increases the number of colposcopy biopsies with minimal improvements in detection of CIN2 +.

  6. [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.

  7. Prevalence characteristics of high-risk human papillomaviruses in women living in Shanghai with cervical precancerous lesions and cancer.

    PubMed

    Gu, Ying; Ma, Chenyun; Zou, Jue; Zhu, Yi; Yang, Rong; Xu, Yan; Zhang, Yu

    2016-04-26

    A complete understanding of the natural history of infection with high-risk human papillomaviruses (HPVs) in cervical cancer requires data from regional and ethnic studies. The prevalence of high-risk HPVs was evaluated retrospectively in 2040 patients with cervicitis, 239 with cervical intraepithelial neoplasia grade 1 (CIN1), 242 with CIN2/3, and 42 patients with invasive squamous cell carcinoma (SCC) based on data from patients who visited our hospital between May 2013 and May 2015. The rates of high-risk HPV infection in patients with cervicitis, CIN1, CIN2/3, and invasive SCC were 40.8%, 74.9%, 70.2%, and 83.3%, respectively. The three most dominant HPV genotypes were HPV16, 58, and 52. HPV16 and HPV58 positivity in cervicitis, CIN1, CIN2/3, and SCC patients were 20.9% and 16.4%, 19.0% and 20.1%, 44.1% and 23.5%, and 60.0% and 31.4%, respectively. Compared to cervicitis, the odds ratios (ORs) for CIN2/3 in HPV16- and HPV58-positive patients were 2.99 (95% confidence interval [CI]: 1.32-4.33) and 1.56 (1.11-3.21), respectively; for SCC, the corresponding values were 5.68 (2.31-7.893) and 2.33 (1.41-3.87). Further identifying of carcinogenic HPVs and a fully aware of regional differences in HPV genotype distribution are tasks of top priority for cervical cancer control and prevention.

  8. The clearance of oral high-risk human papillomavirus infection is impaired by long-term persistence of cervical human papillomavirus infection.

    PubMed

    Louvanto, K; Rautava, J; Syrjänen, K; Grénman, S; Syrjänen, S

    2014-11-01

    Persistence of high-risk (HR-) human papillomavirus (HPV) infection of the uterine cervix increases the risk of cervical cancer. Oral HPV infections are among potential covariates of long-term genotype-specific persistent cervical HR-HPV infections. It is not known whether this persistence reflects inability of the host to reject HPV infections in general. A case-control setting was designed to estimate the covariates of long-term persistent cervical HR-HPV infections using multivariate generalized estimating equation (GEE) models. HPV was detected with PCR using GP05+/GP06+-primers and genotyped for 24 HPVs with a Multimetrix-kit. The cases (n=43) included women who had genotype-specific persistent cervical HR-HPV infection for at least 24 months (24M+) and controls were women who tested repeatedly HPV-negative in their cervical samples (n=52). These women represent a sub-cohort of the Finnish Family HPV Study. The cases differed significantly from the HPV-negative controls in several aspects: they were younger, had a longer mean time to incident oral HPV infection (40.7 versus 23.6 months), longer duration of oral HPV persistence (38.4 versus 14.1 months), and longer time to clearance of their oral HPV infection (50.0 versus 28.2 months). In multivariate GEE analysis, the second pregnancy during the follow up was the only independent predictor with significant protective effect against 24M+ persistent cervical HR-HPV infections, OR of 0.15 (95% CI 0.07-0.34). To conclude, long-term persistent cervical HR-HPV infections are associated with a prolonged clearance of oral HR-HPV infections while new pregnancy protects against persistent cervical HR-HPV infections. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

  9. High-risk human papillomavirus genotypes distribution in a cohort of HIV-positive women living in Europe: epidemiological implication for vaccination against human papillomavirus.

    PubMed

    Konopnicki, Deborah; Manigart, Yannick; Gilles, Christine; Barlow, Patricia; De Marchin, Jérome; Feoli, Francesco; Delforge, Marc; Clumeck, Nathan; De Wit, Stéphane

    2016-01-28

    Worldwide, human papillomavirus (HPV) 16 and 18 represents 70% of high-risk (HR) HPV found in cervical cancer. However HIV-positive women are more frequently infected by HRHPV other than HPV 16 or 18 (OHR). We aimed to analyse the HRHPV genotype distribution in a cohort of HIV-positive women and to estimate the potential protection offered by the different HPV vaccines. HRHPV genotypes by PCR and cytology were assessed in cervical samples from 508 HIV-positive women prospectively followed in Brussels. Women characteristics were as follows: African origin (84%), median age 42 years, median CD4 T 555/μl, 89% under combined antiretroviral therapy and 73% with HIVRNA less than 20 copies/ml. HRHPV prevalence was 23% (116/508): 38% had abnormal cytology, 76% carried OHR without HPV 16 or 18 and 11% had concomitant infection by OHR and HPV 16 or 18. The most frequent HRHPV were HPV52 (19.8%), HPV18 (14.6%), HPV31/35/51/58 (12.1% each), HPV56 (9.9%) and HPV16 (9.5%). Less than 30% of women had their HRHPV genotypes included in the bivalent or quadrivalent vaccines against HRHPV 16 and 18; however, 79% had their HRHPV covered by the ninevalent vaccine against HRHPV 16/18/31/33/45/52/58. The HRHPV genotypes distribution found in these women living in Europe with a successfully treated HIV is similar to the one found in Central Africa with HRHPV other than HPV16 or 18 retrieved in 87%. In this population, the bivalent or quadrivalent vaccines could offer protection in only 30% of women; however this protection could be extended up to 80% with the ninevalent vaccine.

  10. High-risk human papillomavirus detection and related risk factors among pregnant and nonpregnant women in Mexico.

    PubMed

    Hernández-Girón, Carlos; Smith, Jennifer S; Lorincz, Attila; Lazcano, Eduardo; Hernández-Avila, Mauricio; Salmerón, Jorge

    2005-10-01

    Significant differences in human papillomavirus (HPV) prevalence between pregnant and nonpregnant women have been reported. Some studies suggest that physiological processes during pregnancy modify the host-immune response, increasing detectability of high-risk HPV infection as a result of viral reactivation. It remains uncertain, however, whether pregnancy has an effect on HPV DNA positivity as a result of a general lack of data and based on contradictory results found in previous epidemiologic studies. We conducted an epidemiologic study to identify differences in the prevalence of HPV infection between pregnant and nonpregnant women in Mexico. We also investigated the relationship of HPV DNA positivity with socioeconomic, gynecologic, and obstetric risk factors. We screened pregnant and age-matched nonpregnant women for high-risk HPV infection. The study population was clients of the family medicine healthcare services of the Mexican Institute of Social Security in Cuernavaca, Morelos, Mexico. A total of 274 pregnant and 1060 nonpregnant study participants were screened for the presence of high-risk HPV DNA in self-collected specimens by the Hybrid Capture 2 test (HC2; Digene Corp., Gaithersburg, MD). High-risk HPV DNA was detected in 37.2% (95% confidence interval [CI], 31-43%) of pregnant women and in 14.2% (95% CI, 12-16%) of nonpregnant women. Combining both groups for the multivariate analysis, pregnancy was associated with an increased risk for HPV infection (odds ratio, 3.5; CI, 2.7-4.9). Our results are consistent with other studies reporting increased high-risk HPV detection rates among pregnant women. HPV-positive status in pregnant and nonpregnant women appears to be influenced by age. The decrease in HPV positivity by number of pregnancies in both currently pregnant and nonpregnant women is consistent with a possible effect of immune protection as a result of earlier HPV infections. Despite lack of information about a woman's history of sexual

  11. Risk factors for high-risk human papillomavirus infection and cofactors for high-grade cervical disease in Peru.

    PubMed

    Almonte, Maribel; Ferreccio, Catterina; Gonzales, Miguel; Delgado, Jose Manuel; Buckley, C Hilary; Luciani, Silvana; Robles, Sylvia C; Winkler, Jennifer L; Tsu, Vivien D; Jeronimo, Jose; Cuzick, Jack; Sasieni, Peter

    2011-12-01

    To evaluate the association between potential risk factors for high-risk human papillomavirus (HR-HPV) infection and cofactors for cervical intraepithelial lesions grade 2 or worse (CIN2+) in women attending cervical screening in Amazonian Peru. Participants completed a risk factor questionnaire before screening. High-risk human papillomavirus infection was determined by Hybrid Capture II. Logistic regression was used to evaluate associations between potential risk factors for HR-HPV infection and between cofactors and risk of CIN2+ among women with HR-HPV infection. Screening and questionnaires were completed by 5435 women aged 25 to 49 years. The prevalence of HR-HPV was 12.6% (95% confidence interval [CI], 11.8%-13.6%) and decreased by age. Early age at first sexual intercourse and several lifetime sexual partners increased the risk of having HR-HPV (age-adjusted odds ratio [AOR] of age at first sexual intercourse <18 vs ≥20, 1.5; 95% CI, 1.2-2.0; AOR of ≥5 lifetime sexual partners vs 1, 2.1; 95% CI, 1.4-3.2). Among women with HR-HPV infection, those with no schooling (AOR relative to 1-5 years of schooling, 3.2; 95% CI, 1.3-8.3) and those with parity ≥3 (AOR relative to parity <3, 2.6; 95% CI, 1.4-4.9) were at increased risk of CIN2+. The effect of parity was stronger for cancer (AOR of parity ≥3 vs <3, 8.3; 95% CI, 1.0-65.6). Further analysis showed that the association between parity and CIN2+ was restricted to women younger than 40. Most women (83%) had previously been screened. Sixty-four percent of CIN2+ cases detected in this study occurred in women who reported having had a Papanicolaou test in the previous 3 years. Only 4 of 20 cancers were detected in women never screened before. Having had a previous abnormal Papanicolaou test increased the risk of CIN2+ (OR, 16.1; 95% CI, 6.2-41.9). Among women with HR-HPV, high parity (in young women), no schooling, lack of good-quality screening and of adequate follow-up care are the main risk factors for

  12. Vaccine-Relevant Human Papillomavirus (HPV) Infections and Future Acquisition of High-Risk HPV Types in Men

    PubMed Central

    Rositch, Anne F.; Hudgens, Michael G.; Backes, Danielle M.; Moses, Stephen; Agot, Kawango; Nyagaya, Edith; Snijders, Peter J. F.; Meijer, Chris J. L. M.; Bailey, Robert C.; Smith, Jennifer S.

    2012-01-01

    Background.Little is known about type-specific associations between prevalent human papillomavirus (HPV) infections and risk of acquiring other HPV types in men. Data on natural clustering of HPV types are needed as a prevaccine distribution to which postvaccine data can be compared. Methods.Using data from a randomized controlled trial of male circumcision in Kisumu, Kenya, adjusted mean survival ratios were estimated for acquisition of any-HPV, high-risk (HR) HPV, and individual HR-HPV types among men uninfected as compared to those infected with vaccine-relevant HPV types 16, 18, 31, 45, 6, or 11 at baseline. Results.Among 1097 human immunodeficiency virus–negative, uncircumcised men, 2303 incident HPV infections were detected over 2534 person-years of follow-up. Although acquisition of individual HR-HPV types varied by baseline HPV type, there was no clear evidence of shorter times to acquisition among men without vaccine-relevant HPV-16, -18, -31, -45, -6, or -11 infections at baseline, as compared to men who did have these infections at baseline. Conclusions.These prospective data on combinations of HPV infections over time do not suggest the potential for postvaccination HPV type replacement. Future surveillance studies are needed to definitely determine whether elimination of HPV types by vaccination will alter the HPV type distribution in the population. PMID:22711906

  13. Association of High-Risk Human Papillomavirus with Genital Tract Mucosal Immune Factors In HIV-Infected Women

    PubMed Central

    Buckley, Niall; Huber, Ashley; Lo, Yungtai; Castle, Philip E.; Kemal, Kimdar; Burk, Robert D.; Strickler, Howard D.; Einstein, Mark H.; Young, Mary; Anastos, Kathryn; Herold, Betsy C.

    2015-01-01

    Problem High-risk human papillomavirus (HR-HPV) is prevalent in HIV-infected women and may be associated with mucosal changes that promote HIV replication. Method of Study Innate immune molecules, antimicrobial activity, HIV RNA, and HPV DNA genotypes were measured in a cross-sectional study of 128 HIV-infected women categorized into HPV-16 (n=8), other HR-HPV (n=41), and non-HR-HPV controls (n=79). Results Compared to controls, HR-HPV groups had higher plasma viral loads (p=0.004), lower CD4 cells (p=0.02), more genital tract HIV RNA (p=0.03), greater number of different HPV types (p<0.001), higher cervicovaginal lavage (CVL) IL-1α (p=0.03) and human beta defensin 2 (HBD2) (p=0.049), and less anti-HIVBal activity (p=0.03). HPV-16 remained significantly associated with higher HBD2 (p=0.03), higher IL-1α (p=0.009), and lower anti-HIVBaL activity (p=0.03) compared to controls after adjusting for plasma viral load and CD4 T cell count. Conclusion HR-HPV is associated with mucosal changes in HIV-infected women that could adversely impact genital tract health. PMID:26685115

  14. High Risk Human Papillomavirus Infection of the Foreskin in Asymptomatic Men and Patients with Phimosis.

    PubMed

    Afonso, Larissa A; Cordeiro, Thaissa I; Carestiato, Fernanda N; Ornellas, Antonio Augusto; Alves, Gilda; Cavalcanti, Sílvia M B

    2016-06-01

    There has been increasing interest in understanding the natural history of HPV and the diseases that it causes in men. HPV infection is strongly associated with penile cancer, lack of neonatal circumcision and phimosis. We investigated the incidence of HPV infection in asymptomatic men and patients with phimosis. We assessed 110 asymptomatic men and 30 patients who underwent circumcision due to phimosis. DNA was extracted from swabbed samples collected from asymptomatic men and from foreskin samples collected at circumcision. Polymerase chain reaction using consensus primers for detecting HPV-MY09/11 was performed to detect generic HPV DNA. HPV genotyping was done by polymerase chain reaction amplification with primers for the E6 gene DNA sequences HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, HPV35, HPV45 and HPV58. HPV was present in 46.66% of patients with phimosis, of whom 50% had high risk HPV genotypes. Of asymptomatic cases 16.36% were HPV positive but only 1 sample showed high risk HPV. We detected a significantly high rate of HPV genital infection in patients presenting with phimosis compared with asymptomatic men (p = 0.00167). The prevalence of high risk HPV genotypes in patients with phimosis was also statistically significant (p = 0.0004). We found a robust association between phimosis and the genital HPV prevalence in men and a significant frequency of high risk HPV. Other studies are needed to investigate the occurrence of factors that can increase the incidence of penile carcinoma and determine its impact on female genital infection in cervical cancer. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  15. Worldwide Genomic Diversity of the High-Risk Human Papillomavirus Types 31, 35, 52, and 58, Four Close Relatives of Human Papillomavirus Type 16

    PubMed Central

    Calleja-Macias, Itzel E.; Villa, Luisa L.; Prado, Jose C.; Kalantari, Mina; Allan, Bruce; Williamson, Anna-Lise; Chung, Lap-Ping; Collins, Robert J.; Zuna, Rosemary E.; Dunn, S. Terence; Chu, Tang-Yuan; Cubie, Heather A.; Cuschieri, Kate; von Knebel-Doeberitz, Magnus; Martins, Claudia R.; Sanchez, Gloria I.; Bosch, F. Xavier; Munoz, Nubia; Bernard, Hans-Ulrich

    2005-01-01

    Among the more than one hundred formally described human papillomavirus (HPV) types, 18 are referred to as high-risk HPV types due to their association with anogenital cancer. Despite pathogenic similarities, these types form three remotely related taxonomic groups. One of these groups is called HPV species 9 and is formed by HPV-16, the most common and best-studied type, together with HPV-31, -33, -35, -52, -58, and -67. Previous worldwide comparisons of HPV-16 samples showed about 2% nucleotide diversity between isolates, which were subsequently termed variants. The distribution of divergent variants has been found to correlate frequently with the geographic origin and the ethnicity of the infected patients and led to the concept of unique African, European, Asian, and Native American HPV-16 variants. In the current study, we address the question of whether geography and ethnicity also correlate with sequence variations found for HPV-31, -35, -52, and -58. This was done by sequencing the long control region in samples derived from Europe, Asia, and Africa, and from immigrant populations in North and South America. We observed maximal divergence between any two variants within each of these four HPV types ranging from 1.8 to 3.6% based on nucleotide exchanges and, occasionally, on insertions and deletions. Similar to the case with HPV-16, these mutations are not random but indicate a relationship between the variants in form of phylogenetic trees. An interesting example is presented by a 16-bp insert in select variants of HPV-35, which appears to have given rise to additional variants by nucleotide exchanges within the insert. All trees showed distinct phylogenetic topologies, ranging from dichotomic branching in the case of HPV-31 to star phylogenies of the other three types. No clear similarities between these types or between these types and HPV-16 exist. While variant branches in some types were specific for Europe, Africa, or East Asia, none of the four trees

  16. High-risk human papillomavirus in the oral cavity of women with cervical cancer, and their children

    PubMed Central

    2010-01-01

    Background Association of High-risk Human Papillomavirus (HR-HPV) with oral cancer has been established recently. Detecting these viruses in oral cavity is important to prevent oral lesions related to them. The purpose of this study was to evaluate the prevalence of HR-HPV in the oral cavity of women with cervical cancer, and their children. A total of 70 women, previously diagnosed with cervical cancer, and 46 children of these women, born by vaginal delivery only, were selected for this study. Buccal swabs were collected from their oral cavity and HPV detection was carried out using Hybrid Capture 2 high-risk HPV (HC2 HR-HPV) detection system. Results Out of 70 women with cervical cancer, four (5.71%) were found to be positive for HR-HPV in their oral cavity. No association of HR-HPV was found with sociodemographic profile, marital status, reproductive history, tobacco and alcohol usage, contraceptive pills usage, and presence of oral lesions (p>0.05). Among children, HR-HPV in the oral cavity was detected in only 1 of the 46 subjects examined (2.17%). Clinically healthy oral mucosa, without any oral lesions, was observed in all the HR-HPV positive subjects. Conclusion The result of this study showed that there is low, if any, risk of HR-HPV infection in the oral cavity of women with cervical cancer. Further, our study suggests that there is very low risk for children of women with cervical cancer, to acquire and sustain HR-HPV in their oral cavity until childhood or adolescence. PMID:20550718

  17. Evolutionary Ecology of Human Papillomavirus: Trade-offs, Coexistence, and Origins of High-Risk and Low-Risk Types

    PubMed Central

    Gatenby, Robert A.; Giuliano, Anna R.; Brown, Joel S.

    2012-01-01

    Background. We address the ecological and evolutionary dynamics of human papillomavirus (HPV) that lead to the dichotomy between high-risk (HR) and low-risk (LR) types. We hypothesize that HPV faces an evolutionary tradeoff between persistence and per-contact transmission probability. High virion production enhances transmissibility but also provokes an immune response leading to clearance and limited persistence. Alternatively, low virion production increases persistence at the cost of diminished transmission probability per sexual contact. We propose that LR HPV types use the former strategy and that HR types use the latter. Sexual behaviors in a host population determine the success of each strategy. Methods. We develop an evolutionary model of HPV epidemiology, which includes host sexual behavior, and we find evolutionarily stable strategies of HPV. Results. A slow turnover of sexual partners favors HR HPV, whereas high frequency of partner turnover selects for LR. When both sexual behaviors exist as subcultures in a population, disruptive selection can result in the coevolution and ecological coexistence of both HR and LR HPV types. Conclusions. Our results indicate that the elimination of HR HPV through vaccines may alter the evolutionary trajectory of the remaining types and promote evolution of new HR HPV types. PMID:22090448

  18. Sexual behavior and high-risk human papillomavirus in 15- to 22-year-old Lithuanian women.

    PubMed

    Bumbuliene, Zana; Alisauskas, Jonas

    2012-04-01

    We determined the risk of high-risk human papillomavirus (HR-HPV) infection in 169 15- to 22-year-old sexually active Lithuanian women attending two outpatient clinics in Vilnius. The Digene(®) Hybrid Capture II DNA test was used to test for HR-HPV infection on material collected by cervical swabs. The findings were compared with the pattern of sexual behavior as given in questionnaire replies. The overall risk of HR-HPV was 23.1%, but 60.0% in adolescents ≤15 years old. Mean age at first intercourse was 17.1 years; 73.5% of women had only had one sexual partner and 24.5% more than one. The risk of HR-HPV was higher in women with more than one sexual partner, and related to being a smoker and to early age at the first intercourse. Our results confirm that smoking, early coitarche, multiple sexual partners and unprotected vaginal intercourse are related to the risk of HR-HPV infection in young women.

  19. Reliability of the Xpert HPV assay to detect high-risk human papillomavirus DNA in a colposcopy referral population.

    PubMed

    Castle, Philip E; Smith, Katherine M; Davis, Thomas E; Schmeler, Kathleen M; Ferris, Daron G; Savage, Ashlyn H; Gray, Jermaine E; Stoler, Mark H; Wright, Thomas C; Ferenczy, Alex; Einstein, Mark H

    2015-01-01

    The Xpert HPV Assay (Xpert; Cepheid, Sunnyvale, CA) was developed for the multianalytic GeneXpert platform. In a colposcopy referral population of 708 women living in the United States, two cervical specimens, A and B, were collected, and both were tested by the Xpert assay for high-risk human papillomavirus (hrHPV) DNA, permitting an evaluation of its test reliability. Specimen B was also tested by Hybrid Capture 2 (hc2; Qiagen, Germantown, MD) and the cobas HPV Test (cobas; Roche Molecular Systems, Pleasanton, CA). The κ and percent agreement for any hrHPV for the two Xpert results were 0.88 and 94.5%, respectively. There was no statistical difference in testing positive on both specimens by Xpert (P = .62). The sensitivity for detection of cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) was 89.0% using specimen A and 90.4% using specimen B for Xpert, 90.4% for cobas, and 81.6% for hc2. The Xpert assay was sensitive and reliable for the detection of hrHPV and the identification of women with CIN2+. Copyright© by the American Society for Clinical Pathology.

  20. Risk factors for high-risk human papillomavirus detection among HIV-negative and HIV-positive women from Tanzania.

    PubMed

    Dartell, Myassa; Rasch, Vibeke; Munk, Christian; Kahesa, Crispin; Mwaiselage, Julius; Iftner, Thomas; Kjaer, Susanne Krüger

    2013-09-01

    Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. The prevalence is dependent on several known factors notably sexual behavior and age, and factors still under scrutiny. This study aimed to examine risk factors for high-risk (HR) HPV infection among HIV-positive and HIV-negative women from the general population of Tanzania and to assess whether specific risk factors could contribute to the high prevalence of HR HPV infection in older age found in some populations including Tanzanian women. A cross-sectional study of 3699 women from Tanzania was conducted. We obtained information on sociodemographic and lifestyle factors through personal interview. Cervical swabs were collected for detection of HR HPV (Hybrid Capture 2; Qiagen, Hildesheim, Germany) and genotyping (LiPaExtra; Innogenetics, Gent, Belgium). Finally, we obtained a blood sample for HIV testing. HIV positivity was the strongest risk factor for HR HPV (odds ratio, 4.1; 95% confidence interval, 3.3-5.3). Young age, shorter duration of present relationship, and increasing number of sex partners were also associated with higher risk for HR HPV. Among women 20 to 29 years old, especially number of partners (P = 0.005) and HIV positivity (P < 0.0001) determined the risk. In underweight women 50 years or older (P = 0.004) and HIV positivity (P = 0.0009) increased the risk, whereas increasing number of partners was not related to the risk of HR HPV (P = 0.46). Human papillomavirus risk factors among HIV-positive and HIV-negative women were similar, but the strength of association was greater among HIV-positive women, notably for lifetime number of sex partners, time in present relationship, genital warts, and body mass index. We were not able to identify a clear explanation for the high HPV prevalence among older women. However, in the age-stratified analysis, potential indicators of decreased immunity increased the risk for HPV infection among older women, whereas

  1. Cervical Microbiota Associated with Higher Grade Cervical Intraepithelial Neoplasia in Women Infected with High-Risk Human Papillomaviruses.

    PubMed

    Piyathilake, Chandrika J; Ollberding, Nicholas J; Kumar, Ranjit; Macaluso, Maurizio; Alvarez, Ronald D; Morrow, Casey D

    2016-05-01

    It is increasingly recognized that microbes that reside in and on human body sites play major roles in modifying the pathogenesis of several diseases, including cancer. However, specific microbes or microbial communities that can be mechanistically linked to cervical carcinogenesis remain largely unexplored. The purpose of the study was to examine the association between cervical microbiota and high-grade cervical intraepithelial neoplasia (CIN 2+) in women infected with high-risk (HR) human papillomaviruses (HPV) and to assess whether the cervical microbiota are associated with oxidative DNA damage as indicated by the presence of cervical cells positive for 8-hydroxy-2'-deoxyguanosine. The study included 340 women diagnosed with CIN 2+ (cases) and 90 diagnosed with CIN 1 (non-cases). Microbiota composition was determined by Illumina sequencing of the 16S rRNA gene amplified from DNA extracted from cervical mucus samples. Measures of alpha/beta-diversity were not associated with either CIN severity or oxidative DNA damage. However, a cervical mucosal community type (CT) dominated by L. iners and unclassified Lactobacillus spp was associated with CIN 2+ (OR = 3.48; 95% CI, 1.27-9.55). Sequence reads mapping to Lactobacillaceae, Lactobacillus, L. reuteri, and several sub-genus level Lactobacillus operational taxonomic units were also associated with CIN 2+ when examined independently (effect size >2.0; P < 0.05). Our 16S rRNA sequencing results need confirmation in independent studies using whole-genome shotgun sequencing and that would allow sharpening the suggested associations at finer taxonomic levels. Our results provide little evidence that DNA oxidative damage mediates the effect of the microbiome on the natural history of HPV infection and CIN severity. Cancer Prev Res; 9(5); 357-66. ©2016 AACR. ©2016 American Association for Cancer Research.

  2. Human Papillomavirus Vaccine Increases High-Risk Sexual Behaviors: A Myth or Valid Concern

    ERIC Educational Resources Information Center

    Ratanasiripong, Nop T.

    2014-01-01

    In 2006, the first human pappilomavirus (HPV) vaccine was approved for females aged 9 to 26. However, the national HPV vaccination rate among young women has been low. Public concerns were raised in regard to the fact that HPV vaccination might encourage unsafe sex. This cross-sectional study examined the differences in sexual practices between…

  3. Human Papillomavirus Vaccine Increases High-Risk Sexual Behaviors: A Myth or Valid Concern

    ERIC Educational Resources Information Center

    Ratanasiripong, Nop T.

    2014-01-01

    In 2006, the first human pappilomavirus (HPV) vaccine was approved for females aged 9 to 26. However, the national HPV vaccination rate among young women has been low. Public concerns were raised in regard to the fact that HPV vaccination might encourage unsafe sex. This cross-sectional study examined the differences in sexual practices between…

  4. Prevalence and predictors of high-risk human papillomavirus infection in a population-based sample of women in rural Uganda

    PubMed Central

    Asiimwe, Stephen; Whalen, Christopher C; Tisch, Daniel J; Tumwesigye, Elioda; Sethi, Ajay K

    2010-01-01

    Summary High-risk genital human papillomavirus (HPV) infection is aetiologically linked to cervical cancer; however, data on the prevalence and determinants of high-risk HPV infection in Uganda are limited. We conducted a population-based cross-sectional survey among 18–49-year-old women in rural Southwest Uganda. The primary outcome was presence or absence of high-risk HPV DNA (for genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 or 68) in the genital secretions as determined by HPV DNA Hybrid Capture 2 assay (Digene Corp, Beltsville, MD, USA). In 314 women who participated, the prevalence of high-risk HPV was 17.2% (54/314; 95% confidence interval [CI]: 13–21). Older women had a lower proportion of high-risk HPV infection; with a 9% decrease in the odds ratio (OR) of high-risk HPV infection per year increase in age (OR = 0.91; 95% CI: 0.86, 0.96). The odds of detecting high-risk HPV infection was higher among women who were previously tested positive for HIV (OR = 12.1; 95% CI: 2.8, 52.3). In this population of rural Ugandan women, the prevalence of high-risk cervical HPV infection was high. Information on predictors of high-risk HPV infection and intention to receive a vaccine can guide future immunization initiatives for young sexually active women. PMID:18725551

  5. [Population-based study of human papillomavirus infection in high-risk area for cervical cancer in Shanxi Province, China].

    PubMed

    Shen, Yan-hong; Chen, Feng; Huang, Man-ni; Liu, Bin; Wang, Xi-xia; Zhao, Fang-hui; Li, Shu-min; Li, Nan; Wu, Ling-ying; Rong, Shou-de; Zhang, Wen-hua; Ren, Sheng-da; Huang, Rui-de; Qiao, You-lin

    2003-08-01

    To investigate the prevalence of oncogenic type of human papillomavirus (HPV) infection and identify the high risk population for conducting immuno/chemoprevention of cervical cancer. All married women aged 30 to 50 with no history of hysterectomy, pelvic radiation and non-pregnant from certain villages of Xiangyuan and Yangcheng County were invited. This study was conducted through two phases. In phase one, subjects sampled the vaginal secretions using the collectors after signing the informed consent. And physicians sampled exfoliated cells from cervix in the phase two. All the specimens were tested with the Hybrid Capture 2 test. The data was managed and analyzed by VFP and SPSS software. There were 9,683 women participated in this study. Local women welcomed this study and population compliance rate was 75.4%. In tested population, we found 2,666 subjects of HPV DNA positive and HPV prevalence was 27.5%. The rates of different age group were 24.5% (30-34 yrs), 27.4% (35-39 yrs), 28.2% (40-44 yrs), 27.4% (45-50 yrs) respectively and had no significant differences (P = 0.604). The rates were slightly increased with the higher education level and had no differences (P = 0.106). The rate in mountain areas was higher than that in half-mountain areas (P = 0.001). The prevalence of HPV infection is indeed high in this region. Local women and health professionals welcome the activities of cervical cancer screening and prevention. It is an emergent task to improve their sanitary condition and prevent them from cervical cancer in these women. A women health cohort is established successfully among high HPV exposed women in rural China. The extensive biologic specimen repository has been successfully established to simultaneously study the etiology, early detection, and immuno/chemoprevention of cervical cancer.

  6. The reliability of high-risk human papillomavirus detection by Aptima HPV assay in women with ASC-US cytology.

    PubMed

    Castle, Philip E; Reid, Jennifer; Dockter, Janel; Getman, Damon

    2015-08-01

    The Aptima HPV assay (AHPV) for high-risk human papillomavirus (hrHPV), and the Aptima HPV 16 18/45 Genotype assay (AHPV GT) for HPV16 and for HPV18 and/or HPV45 (HPV18/45) genotypes are approved for cervical cancer screening by the U.S. Food and Drug Administration. There are limited data on the reliability of these tests for detection of hrHPV, HPV16, and HPV18/45. To assess the reliability of AHPV and AHPV GT on paired specimens from women with atypical squamous cells of undetermined significance (ASC-US) cytology. In a population of women with ASC-US cytology (n=988), cervical specimens were collected at a routine screening baseline visit and at the colposcopy visit that occurred a median of 29 days later. Specimens were tested by AHPV and if positive, by AHPV GT. There was no significant difference in the percent AHPV positive between the colposcopy and baseline specimens (41.9% vs. 43.0%, respectively, p=0.3). The percent agreement, percent positive agreement, and the kappa value were 88.6%, 76.3%, and 0.766, respectively. There were no significant differences between AHPV testing of the colposcopy and baseline specimen in the sensitivity (95.2% vs. 92.9%, respectively, p=1) and specificity (60.5% vs. 59.2%, respectively, p=0.3) for CIN3+. Comparing the hierarchical AHPV and AHPV GT results on the two specimens, the percent exact agreement was 86.2%, the percent positive agreement was 68.4%, and the kappa value was 0.746. AHPV and AHPV GT demonstrated good reliability for hrHPV detection and risk stratification. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  7. p16 Expression Is Not a Surrogate Marker for High-Risk Human Papillomavirus Infection in Periocular Sebaceous Carcinoma.

    PubMed

    Stagner, Anna M; Afrogheh, Amir H; Jakobiec, Frederick A; Iacob, Codrin E; Grossniklaus, Hans E; Deshpande, Vikram; Maske, Christopher; Hiss, Donovan C; Faquin, William C

    2016-10-01

    To evaluate the role of high-risk human papillomavirus (HR-HPV) infection in periocular sebaceous carcinoma (SC) using multiple methods of detection, and to determine whether p16 overexpression is present and can be used as a surrogate marker for HR-HPV. Retrospective observational case series with laboratory investigations. Unstained paraffin sections of 35 cases of periocular SC were analyzed with immunohistochemistry for p16 and subjected to polymerase chain reaction (PCR) for HR-HPV. A subset of 18 lesions that were p16-positive was further studied with a novel method of mRNA in situ hybridization (ISH) for the detection of transcriptionally active HR-HPV, an advanced technique with an enhanced sensitivity and specificity. The clinical findings were in keeping with those of comparable earlier studies. Strong immunohistochemical p16 positivity (meeting the criterion of >70% nuclear and cytoplasmic staining) was present in 29 of 35 cases of periocular SC (82.9%). The selected 18 p16-positive cases tested were negative for HR-HPV using mRNA ISH. PCR yielded unequivocal results with adequate DNA isolated in 24 cases, 23 of which were negative for HR-HPV. One case was positive for HPV type 16, which was found to be a false positive as collaterally determined by mRNA ISH negativity. No evidence was found for HR-HPV as an etiologic agent in the development of periocular SC using multiple modalities to maximize sensitivity and specificity and reduce the limitations of any single test. p16 overexpression is common in periocular SC but unrelated to HR-HPV status. Although p16 may be used as a surrogate marker for HR-HPV status in other tissue sites, this interpretation of p16 positivity is not applicable to periocular SC. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Evaluation of any or type-specific persistence of high-risk human papillomavirus for detecting cervical precancer.

    PubMed

    Marks, Morgan A; Castle, Philip E; Schiffman, Mark; Gravitt, Patti E

    2012-02-01

    High-risk human papillomavirus (HR-HPV) testing is increasingly important. We therefore examined the impact on accuracy of repeated versus one-time testing, type-specific versus pooled detection, and assay analytic sensitivity. By using a nested case-control design from the ASCUS-LSIL Triage Study, we selected women with incident cervical intraepithelial neoplasia grade 2 or grade 3 (CIN2/3; n = 325) and a random sample of women with

  9. Role of mucosal high-risk human papillomavirus types in head and neck cancers in central India.

    PubMed

    Gheit, Tarik; Anantharaman, Devasena; Holzinger, Dana; Alemany, Laia; Tous, Sara; Lucas, Eric; Prabhu, Priya Ramesh; Pawlita, Michael; Ridder, Ruediger; Rehm, Susanne; Bogers, Johannes; Maffini, Fausto; Chiocca, Susanna; Lloveras, Belén; Kumar, Rekha Vijay; Somanathan, Thara; de Sanjosé, Silvia; Castellsagué, Xavier; Arbyn, Marc; Brennan, Paul; Sankaranarayanan, Rengaswamy; Pillai, Madhavan Radhakrishna; Gangane, Nitin; Tommasino, Massimo

    2017-07-01

    Mucosal high-risk (HR) human papillomaviruses (HPV) cause a subset of head and neck cancers (HNC). The HPV-attributable fraction of HNC varies substantially between countries. Although HNC has a very high incidence in the Indian subcontinent, information on the contribution of HPV infection is limited. Here, we evaluated the HPV-attributable fraction in HNC (N = 364) collected in a central region of India. HNC from three different anatomical subsites were included, namely, oral cavity (n = 252), oropharynx (n = 53) and hypopharynx/larynx (n = 59). In this retrospective study, HPV-driven HNC were defined by presence of both viral DNA and RNA. Overexpression of p16(INK4a) was also evaluated. HR-HPV DNA was detected in 13.7% of the cases; however, only 2.7% were positive for both HPV DNA and RNA. The highest percentage of HPV DNA/RNA double positivity was found in oropharynx (9.4%), followed by larynx (1.7%) and oral cavity (1.6%) (p = 0.02). More than half of HPV DNA/RNA-positive cases were p16(INK4a) -negative, while a considerable number of HPV RNA-negative cases were p16(INK4a) -positive (17.9%). HPV16 was the major type associated with HNC (60.0%), although cases positive for HPV18, 35 and 56 were also detected. Our data indicate that the proportion and types of mucosal HR-HPV associated with HNC in this central Indian region differ from those in other (developed) parts of the world. This may be explained by differences in smoking and/or sexual behaviour compared with North America and northern Europe. Moreover, we show that p16(INK4a) staining appeared not to be a good surrogate marker of HPV transformation in the Indian HNC cases. © 2017 UICC.

  10. Cross-protection of the Bivalent Human Papillomavirus (HPV) Vaccine Against Variants of Genetically Related High-Risk HPV Infections

    PubMed Central

    Harari, Ariana; Chen, Zigui; Rodríguez, Ana Cecilia; Hildesheim, Allan; Porras, Carolina; Herrero, Rolando; Wacholder, Sholom; Panagiotou, Orestis A.; Befano, Brian; Burk, Robert D.; Schiffman, Mark

    2016-01-01

    Background. Results from the Costa Rica Vaccine Trial (CVT) demonstrated partial cross-protection by the bivalent human papillomavirus (HPV) vaccine, which targets HPV-16 and HPV-18, against HPV-31, -33, and -45 infection and an increased incidence of HPV-51 infection. Methods. A study nested within the CVT intention-to-treat cohort was designed to assess high-risk HPV variant lineage–specific vaccine efficacy (VE). The 2 main end points were (1) long-term incident infections persisting for ≥2 years and/or progression to high-grade squamous intraepithelial lesions (ie, cervical intraepithelial neoplasia grade 2/3 [CIN 2/3]) and (2) incident transient infections lasting for <2 years. For efficiency, incident infections due to HPV-16, -18, -31, -33, -35, -45, and -51 resulting in persistent infection and/or CIN 2/3 were matched (ratio, 1:2) to the more-frequent transient viral infections, by HPV type. Variant lineages were determined by sequencing the upstream regulatory region and/or E6 region. Results. VEs against persistent or transient infections with HPV-16, -18, -33, -35, -45, and -51 did not differ significantly by variant lineage. As the possible exception, VEs against persistent infection and/or CIN 2/3 due to HPV-31 A/B and HPV-31C variants were −7.1% (95% confidence interval [CI], −33.9% to 0%) and 86.4% (95% CI, 65.1%–97.1%), respectively (P = .02 for test of equal VE). No difference in VE was observed by variant among transient HPV-31 infections (P = .68). Conclusions. Overall, sequence variation at the variant level does not appear to explain partial cross-protection by the bivalent HPV vaccine. PMID:26518044

  11. Cross-protection of the Bivalent Human Papillomavirus (HPV) Vaccine Against Variants of Genetically Related High-Risk HPV Infections.

    PubMed

    Harari, Ariana; Chen, Zigui; Rodríguez, Ana Cecilia; Hildesheim, Allan; Porras, Carolina; Herrero, Rolando; Wacholder, Sholom; Panagiotou, Orestis A; Befano, Brian; Burk, Robert D; Schiffman, Mark

    2016-03-15

    Results from the Costa Rica Vaccine Trial (CVT) demonstrated partial cross-protection by the bivalent human papillomavirus (HPV) vaccine, which targets HPV-16 and HPV-18, against HPV-31, -33, and -45 infection and an increased incidence of HPV-51 infection. A study nested within the CVT intention-to-treat cohort was designed to assess high-risk HPV variant lineage-specific vaccine efficacy (VE). The 2 main end points were (1) long-term incident infections persisting for ≥2 years and/or progression to high-grade squamous intraepithelial lesions (ie, cervical intraepithelial neoplasia grade 2/3 [CIN 2/3]) and (2) incident transient infections lasting for <2 years. For efficiency, incident infections due to HPV-16, -18, -31, -33, -35, -45, and -51 resulting in persistent infection and/or CIN 2/3 were matched (ratio, 1:2) to the more-frequent transient viral infections, by HPV type. Variant lineages were determined by sequencing the upstream regulatory region and/or E6 region. VEs against persistent or transient infections with HPV-16, -18, -33, -35, -45, and -51 did not differ significantly by variant lineage. As the possible exception, VEs against persistent infection and/or CIN 2/3 due to HPV-31 A/B and HPV-31C variants were -7.1% (95% confidence interval [CI], -33.9% to 0%) and 86.4% (95% CI, 65.1%-97.1%), respectively (P = .02 for test of equal VE). No difference in VE was observed by variant among transient HPV-31 infections (P = .68). Overall, sequence variation at the variant level does not appear to explain partial cross-protection by the bivalent HPV vaccine. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  12. Factors associated with type-specific persistence of high-risk human papillomavirus infection: A population-based study.

    PubMed

    Stensen, Signe; Kjaer, Susanne K; Jensen, Signe M; Frederiksen, Kirsten; Junge, Jette; Iftner, Thomas; Munk, Christian

    2016-01-15

    Persistent genital infection with high-risk (HR) human papillomavirus (HPV) is a prerequisite for cervical cancer development. The aim of this study was to identify factors associated with type-specific persistence of HR HPV infections. From a population-based cohort of 40,399 women participating in cervical cancer screening established during 2002-2005, we selected all HR HPV-positive women (N = 7,778). During follow-up (2005-2008), we collected cervical samples from these women and tested them for HPV DNA to determine type-specific HR HPV persistence in the interval 1-4.5 years after enrolment. Data on hospitalisations, prescriptions and socioeconomic factors were obtained from nationwide registers. Women with abnormal cytology at baseline or who had undergone conisation during follow-up were excluded. Factors associated with persistence were identified by logistic regression analysis. The overall rate of HR HPV persistence was 31.4%. The risk for persistence was significantly increased among women with a previous episode of genital warts (OR, 1.35; 95% CI, 1.04-1.74), current use of oral contraceptives (OR, 1.35; 95% CI, 1.13-1.63) or use of systemic glucocorticoids (OR, 2.04; 95% CI, 1.16-3.56). The number of pregnancies or births or use of a hormonal intrauterine device, hormonal therapy or nonsteroidal anti-inflammatory drugs was not associated with risk for HR HPV persistence. A history of genital warts and current use of oral contraceptives or systemic glucocorticoids increased the risk, potentially indicating a decreased immune response to HPV infection. These findings suggest that host immune response characteristics are important in HR HPV persistence and consequently in cervical cancer development. © 2015 UICC.

  13. [Distribution of serum antibodies against human papillomavirus 16 and 18 among high-risk women to cervical cancer].

    PubMed

    Fei, Mandong; Li, Jiayuan; Du, Jingchang; You, Jia; Zhang, Shaokai; He, Wei; Kang, Leni; Zhao, Fanghui; Qiao, Youlin; Si, Yuzhi; Fan, Xiaoping; Chen, Wen

    2014-05-01

    To explore the distribution of serum antibodies against human papillomavirus (HPV) 16/18 among women at high-risk for cervical cancer. All women when tested positive for anyone of the cervical cancer screening programs, from Xinmi county of Henan province in 2011, were recruited as the subjects of this study. Cervical exfoliated cells were collected, using cervical brush for HPV DNA testing, and 10 ml venous blood was drawn for HPV-16, 18 serum antibodies testing, by enzyme-linked immunosorbent assay. Among the 952 women under study, 230 cases (24.2%)showed HPV DNA positive, with positivity rates of HPV16 and 18 L1 virus-like particle (VLP)antibodies as 23.2% and 6.5%, respectively. The overall positivity rate of any type of HPV16, 18 VLP antibodies was 26.8% . Geometric means of HPV16, 18 VLP antibody titers were 79.1 (Yangshengtang Unit,YU/ml) and 125.0(YU/ml). Positivity rate of HPV16 antibody was significantly associated with age, viral load of HPV DNA, and cervical lesion severity (P < 0.05). Seropositivity of HPV18 was also increasing with the increase of viral load (P < 0.01) with different cervical lesion significantly showing different titer of HPV18 antibody (P < 0.01). Based on the results of HPV DNA detection among the two years of study, women with HPV persistent infection showed significant higher positive rate of HPV16/18 antibodies than women who did not have HPV infection or emerging infection (P < 0.001). When comparing to those women without HPV infection, the ones with transient infection showed higher seropositivity rates on both HPV16 antibodies and titer of HPV16 antibody (P < 0.001). Seroprevalence rates on HPV16 and 18 among the unvaccinated high-risk women in Henan were high. Prevalence of both HPV16 and 18 antibodies were correlated with age, viral load, cervical lesion and history of infection.Women with high viral load, high grade cervical lesion or history of infection would more likely to be seropositive.

  14. [Investigation on the prevalence of high risk human papillomavirus and cervical cancer among adult women, in Shenzhen].

    PubMed

    DU, Hui; Wu, Rui-fang; Tang, Hui-ru; Wu, Lan-na; Zhang, Li-jie; Liu, Zhi-hong; Li, Juan; Li, Rui-zhen; Wang, Guo-ping; Zhou, Yan-qiu; Wang, Chun; Weng, Lei-ming

    2012-08-01

    To investigate the prevalence of high risk human papillomavirus (HPV) genital infection and cervical cancer in adult women from Shenzhen. Cluster sampling was used to investigate the prevalence of HPV infection and cervical cancer from women aged 20 - 59 years old living in Luohu, Futian, Nanshan, Longgang and Baoan districts in Shenzhen from April 2006 to April 2010. All women were detected for liquid-based cytology test (LCT) or Thinprep cytologic test (TCT) and high-risk HPV-DNA test with hybrid capture II (HC-II). All women with ≥ ASC-US by cytology and/or a positive HC-II test were asked to return for colposcopy and four-quadrant biopsy. Endocervical curettage was performed. Pathological finding were used as the gold standard of the diagnosis of cervical intraepithelial neoplasia. 10 210 women were involved in the study and 10 017 of them having completed data. The overall positive rate of high-risk HPV-DNA was 16.29%. HPV positive rates in 20-, 30-, 35-, 40-, 45-, 50-59 age groups were 17.37%, 15.59%, 16.33%, 14.74%, 17.16% and 17.98%, respectively. The curve of HPV infection rates in different age groups appeared a 'W' shape. HPV infection rates in the 25-years-olds and 50-59 year-olds groups were significantly higher than the other age groups (χ(2) = 4.50, P = 0.03). The overall prevalence rate of cervical intraepithelial lesions (CIN) was 7.52%, of which the prevalence rates of low-grade cervical intraepithelial lesions (CIN I) was 5.32% high-grade cervical intraepithelial lesions (CIN II/III) was 2.21%, cervical cancer was 0.12%. The prevalence of CIN I was significantly higher than the CIN II/III (χ(2) = 134.15, P < 0.001). The prevalence of cervical cancer in 45-age group was 0.12%, the highest. HPV infection rates increased with the grades of cervical lesions including women without CIN as 44.31%, in CINI as 70.73%, in CINII as 86.73%, and in CIN III as 96.75% and in cancer as 100.00%. The HPV infection rates were different in districts (χ(2) = 17

  15. Can human papillomavirus (HPV) genotyping classify non-16/18 high-risk HPV infection by risk stratification?

    PubMed

    Sung, Yeoun Eun; Ki, Eun Young; Lee, Youn Soo; Hur, Soo Young; Lee, Ahwon; Park, Jong Sup

    2016-11-01

    Infection with high-risk genotypes of human papillomavirus (HR-HPV) is the major cause of invasive cervical cancers. HPV-16 and HPV-18 are known to be responsible for two-thirds of all invasive cervical carcinomas, followed by HPV-45, -31, and -33. Current guidelines only differentiate HPV-16/18 (+) by recommending direct colposcopy for treatment. We tried to evaluate whether there are differences in risk among 12 non-16/18 HR-HPV genotypes in this study. The pathology archive database records of 1,102 consecutive gynecologic patients, who had results for cervical cytology and histology and for HPV testing, as determined by HPV 9G DNA chip, were reviewed. Among the 1,102 patients, 346 were non-16/18 HR-HPV (+) and 231 were HPV-16/18 (+). We calculated the odds ratios for ≥cervical intraepithelial neoplasia 2 (CIN 2) of 14 groups of each HR-HPV genotype compared with a group of HR-HPV (-) patients. Based on the odds ratio of each genotype, we divided patients with non-16/18 HR-HPV genotypes (+) into two groups: HPV-31/33/35/45/52/58 (+) and HPV-39/51/56/59/66/68 (+). The age-adjusted odds ratios for ≥CIN 2 of the HPV-31/33/35/45/52/58 (+) and HPV-39/51/56/59/66/68 (+) groups compared with a HR-HPV (-) group were 11.9 (95% CI, 7.6 to 18.8; p<0.001) and 2.4 (95% CI, 1.4 to 4.3; p<0.001), respectively, while that of the HPV-16/18 (+) group was 18.1 (95% CI, 11.6 to 28.3; p=0.003). The 12 non-16/18 HR-HPV genotypes can be further categorized (HPV-31/33/35/45/52/58 vs. HPV-39/51/56/59/66/68) by risk stratification. The HPV-31/33/35/45/52/58 genotypes might need more aggressive action. Large scale clinical trials or cohort studies are necessary to confirm our suggestion.

  16. Prevalence and risk factors for oncogenic human papillomavirus infections in high-risk mid-adult women.

    PubMed

    Winer, Rachel L; Hughes, James P; Feng, Qinghua; Xi, Long Fu; Lee, Shu-Kuang; O'Reilly, Sandra F; Kiviat, Nancy B; Koutsky, Laura A

    2012-11-01

    The epidemiology of high-risk (hr) human papillomavirus (HPV) infections in mid-adult women with new sex partners is undefined. We analyzed baseline data from 518 25- to 65-year-old women online daters. Women were mailed questionnaires and kits for self-collecting vaginal specimens for polymerase chain reaction-based hrHPV testing. Risk factors for infection were identified using Poisson regression models to obtain prevalence ratios (PRs). The prevalence of hrHPV infection was 35.9%. In multivariate analysis restricted to sexually active women, the likelihood of hrHPV infection was associated with abnormal Papanicolaou test history (PR = 1.42, 95% confidence interval [CI]: 1.10-1.84), lifetime number of sex partners >14 (compared with 1-4; PR = 2.13, 95% CI: 1.13-4.02 for 15-24 partners; and PR = 1.91, 95% CI: 1.00-3.64 for ≥25 partners), male partners with ≥1 concurrent partnership (PR = 1.34, 95% CI: 1.05-1.71), and male partners whom the subject met online (PR = 1.39, 95% CI: 1.08-1.79). Age was inversely associated with infection only in women who were sexually inactive (PR = 0.67 per 5-year age difference, adjusted for Papanicolaou history and lifetime number of partners). Compared with sexually inactive women, the likelihood of infection increased with increasing risk level (from low-risk to hr partners; P < 0.0001 by trend test). In multivariate analysis, infection with multiple versus single hrHPV types was inversely associated with ever having been pregnant (PR = 0.64, 95% CI: 0.46-0.90) and recent consistent condom use (PR = 0.56, 95% CI: 0.32-0.97), and positively associated with genital wart history (PR = 1.43, 95% CI: 1.03-1.99). Measures of both cumulative and recent sexual history were associated with prevalent hrHPV infection in this hr cohort of mid-adult women.

  17. Mycoplasma hominis and Mycoplasma genitalium in the Vaginal Microbiota and Persistent High-Risk Human Papillomavirus Infection.

    PubMed

    Adebamowo, Sally N; Ma, Bing; Zella, Davide; Famooto, Ayotunde; Ravel, Jacques; Adebamowo, Clement

    2017-01-01

    Recent studies have suggested that the vaginal microenvironment plays a role in persistence of high-risk human papillomavirus (hrHPV) infection and thus cervical carcinogenesis. Furthermore, it has been shown that some mycoplasmas are efficient methylators and may facilitate carcinogenesis through methylation of hrHPV and cervical somatic cells. We examined associations between prevalence and persistence of Mycoplasma spp. in the vaginal microbiota, and prevalent as well as persistent hrHPV infections. We examined 194 Nigerian women who were tested for hrHPV infection using SPF25/LiPA10 and we identified Mycoplasma genitalium and Mycoplasma hominis in their vaginal microbiota established by sequencing the V3-V4 hypervariable regions of the 16S rRNA gene. We defined the prevalence of M. genitalium, M. hominis, and hrHPV based on positive result of baseline tests, while persistence was defined as positive results from two consecutive tests. We used exact logistic regression models to estimate associations between Mycoplasma spp. and hrHPV infections. The mean (SD) age of the study participants was 38 (8) years, 71% were HIV positive, 30% M. genitalium positive, 45% M. hominis positive, and 40% hrHPV positive at baseline. At follow-up, 16% of the women remained positive for M. genitalium, 30% for M. hominis, and 31% for hrHPV. There was a significant association between persistent M. hominis and persistent hrHPV (OR 8.78, 95% CI 1.49-51.6, p 0.01). Women who were positive for HIV and had persistent M. hominis had threefold increase in the odds of having persistent hrHPV infection (OR 3.28, 95% CI 1.31-8.74, p 0.008), compared to women who were negative for both. We found significant association between persistent M. hominis in the vaginal microbiota and persistent hrHPV in this study, but we could not rule out reverse causation. Our findings need to be replicated in larger, longitudinal studies and if confirmed, could have important diagnostic and therapeutic

  18. High-risk human papillomavirus viral load and persistence among heterosexual HIV-negative and HIV-positive men.

    PubMed

    Grabowski, Mary K; Gray, Ronald H; Serwadda, David; Kigozi, Godfrey; Gravitt, Patti E; Nalugoda, Fred; Reynolds, Steven J; Wawer, Maria J; Watya, Stephen; Quinn, Thomas C; Tobian, Aaron A R

    2014-06-01

    High-risk human papillomavirus (HR-HPV) viral load is associated with HR-HPV transmission and HR-HPV persistence in women. It is unknown whether HR-HPV viral load is associated with persistence in HIV-negative or HIV-positive men. HR-HPV viral load and persistence were evaluated among 703 HIV-negative and 233 HIV-positive heterosexual men who participated in a male circumcision trial in Rakai, Uganda. Penile swabs were tested at baseline and 6, 12 and 24 months for HR-HPV using the Roche HPV Linear Array, which provides a semiquantitative measure of HPV shedding by hybridisation band intensity (graded: 1-4). Prevalence risk ratios (PRR) were used to estimate the association between HR-HPV viral load and persistent detection of HR-HPV. HR-HPV genotypes with high viral load (grade:3-4) at baseline were more likely to persist than HR-HPV genotypes with low viral load (grade: 1-2) among HIV-negative men (month 6: adjPRR=1.83, 95% CI 1.32 to 2.52; month 12: adjPRR=2.01, 95% CI 1.42 to 3.11), and HIV-positive men (month 6: adjPRR=1.33, 95% CI 1.06 to 1.67; month 12: adjPRR=1.73, 95% CI 1.18 to 2.54). Long-term persistence of HR-HPV was more frequent among HIV-positive men compared with HIV-negative men (month 24: adjPRR=2.27, 95% CI 1.47 to 3.51). Persistence of newly detected HR-HPV at the 6-month and 12-month visits with high viral load were also more likely to persist to 24 months than HR-HPV with low viral load among HIV-negative men (adjPRR=1.67, 95% CI 0.88 to 3.16). HR-HPV genotypes with high viral load are more likely to persist among HIV-negative and HIV-positive men, though persistence was more common among HIV-positive men overall. The results may explain the association between high HR-HPV viral load and HR-HPV transmission. 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.

  19. High-risk human papillomavirus detection in oropharyngeal, nasopharyngeal, and, oral cavity cancers: Comparison of multiple methods

    PubMed Central

    Walline, Heather M; Komarck, Chris; McHugh, Jonathan B; Byrd, Serena A; Spector, Matthew E; Hauff, Samantha J.; Graham, Martin P; Bellile, Emily; Moyer, Jeffrey S; Prince, Mark E; Wolf, Gregory T; Chepeha, Douglas B; Worden, Francis P; Stenmark, Matthew H; Eisbruch, Avraham; Bradford, Carol R; Carey, Thomas E

    2014-01-01

    Importance Human papillomaviruses are now recognized as an etiologic factor in a growing subset of head and neck cancers and have critical prognostic importance that affects therapeutic decision making. There is no universally accepted gold standard for high-risk HPV (hrHPV) assessment in formalin-fixed, paraffin-embedded (FFPE) tissue specimens, nor is there a clear understanding of the frequency or role of hrHPV in sites other than oropharynx. Objective To determine the optimal assessment of hrHPV in FFPE head and neck tumors. Design Assessment of hrHPV by p16 immunohistochemical staining, in situ hybridization (ISH), and PCR-MassArray (PCR-MA), with L1 PGMY-PCR (PGMY-PCR) and sequencing to resolve method discordance, was applied to 338 FFPE oropharyngeal, nasopharyngeal, and oral cavity tumors. Relative sensitivity and specificity were compared to develop a standard optimal test protocol. Setting Large Midwestern referral center. Participants Tissue specimens from 338 head and neck cancer patients treated during the period 2001-2011 in the departments of Otolaryngology, Radiation Oncology and Medical Oncology. Patients with oropharyngeal and oral cancer were consented for IRB approved study through the Head and Neck SPORE. Tissue blocks from nasopharyngeal cancer patients were retrieved from pathology archives under IRB approval for existing tissue and data. Intervention Patients received standard therapy. Main outcomes and measurements Optimal hrHPV identification, detection, and activity in head and neck cancers. Results Using combined PCR-MA with PGMY-PCR and sequencing for conclusive results, we found PCR-MA to have 99.5% sensitivity and 100% specificity, p16 to have 94.2% sensitivity and 85.5% specificity, and ISH to have 82.9% sensitivity and 81% specificity. Among HPV-positive tumors, HPV16 was most frequently detected, but 10 non-HPV16 types accounted for 6-50% of tumors, depending on site. Overall, 86% of oropharynx, 50% of nasopharynx and 26% of oral

  20. The College of American Pathologists' first 3 years' experience with high-risk human papillomavirus proficiency testing for cytology and other laboratories.

    PubMed

    Moriarty, Ann T; Bentz, Joel S; Winkler, Barbara; Fischer, Andrew H; Laucirica, Rodolfo; Souers, Rhona J; Thomas, Nicole; Zhao, Chengquan

    2013-05-01

    The College of American Pathologists (CAP) Human Papillomavirus (High-Risk) Survey for Cytopathology and Other Laboratories (CHPV) meets the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) requirements for 5 proficiency testing challenges analyzed 3 times per year. This study reports laboratory performance for CHPV from 2008 through 2010. To identify trends in proficiency testing performance for subscribers to the CAP CHPV. CHPV responses were evaluated by using a nonlinear mixed model (significance level of .05) with a 2-factor interaction term and repeated measures component, comparing year, media, method, and intended response. Media types included Digene transport, SurePath, ThinPrep media, or a mixture of media types. Proficiency testing challenges validated at 80% consensus. All challenges validated; 476 laboratories submitted 14 911 responses with 14 620 correct responses (98%). There were no differences between positive or negative challenges, or rate of correct responses; significant differences existed between media types by year and methods. Digene and ThinPrep media performed better than SurePath (P < .001; P = .03). There was a statistically significant difference between methods (P < .001); "other commercial kits," "other (noncommercial)" tests, and Third Wave performed more poorly than others. Laboratories performed well when testing for human papillomavirus in CHPV during a period of 3 years. All challenges performed to the 80% threshold. Significant differences were found between methods and media. The CAP CHPV survey provides useful information for laboratories choosing human papillomavirus testing methods.

  1. [Human papillomaviruses].

    PubMed

    Gross, G

    2003-10-01

    Human papillomaviruses (HPV) infect exclusively the basal cells of the skin and of mucosal epithelia adjacent to the skin such as the mouth, the upper respiratory tract, the lower genital tract and the anal canal. HPV does not lead to a viremia. Basically there are three different types of HPV infection: Clinically visible lesions, subclinical HPV infections and latent HPV infections. Distinct HPV types induce morphologically and prognostically different clinical pictures. The most common HPV associated benign tumor of the skin is the common wart. Infections of the urogenitoanal tract with specific HPV-types are recognised as the most frequent sexually transmitted viral infections. So-called "high-risk" HPV-types (HPV16, 18 and others) are regarded by the world health organisation as important risk-factors for the development of genital cancer (mainly cervical cancer), anal cancer and upper respiratory tract cancer in both genders. Antiviral substances with a specific anti-HPV effect are so far unknown. Conventional therapies of benign skin warts and of mucosal warts are mainly nonspecific. They comprise tissue-destroying therapies such as electrocautery, cryotherapy and laser. In addition cytotoxic substances such as podophyllotoxin and systemic therapy with retinoids are in use. Systemically and topically administered immunotherapies represent a new approach for treatment. Both interferons and particularly the recently developed imiquimod, an interferon-alpha and cytokine-inductor lead to better results and are better tolerated then conventional therapies. HPV-specific vaccines have been developed in the last 5 years and will be used in future for prevention and treatment of benign and malignant HPV-associated tumors of the genitoanal tract in both sexes.

  2. Type-specific prevalence of high-risk human papillomavirus by cervical cytology and age: Data from the health check-ups of 7,014 Korean women.

    PubMed

    Kim, Min-Jeong; Kim, Jin Ju; Kim, Sunmie

    2013-03-01

    We investigated the type-specific high-risk human papillomavirus (HPV) prevalence and distribution according to cervical cytology and age in healthy Korean women. A retrospective cross-sectional study was conducted with 7,014 consecutive subjects undergoing both liquid-based cervical cytology and HPV genotyping test by DNA chip for cervical cancer screening. The type-specific prevalence and distribution of individual high-risk HPV types were assessed according to cervical cytology and age groups (<30, 30-39, 40-49, 50-59, and ≥60 years old). In total, the most common HPV genotype was HPV58 (23.9% of all high-risk HPV-positive subjects), followed by HPV16 (21.8%), HPV52 (16.6%), and HPV18 (11.7%). Regarding cervical cytology and age groups, the proportion of HPV56 strongly increased with the increasing severity of cervical cytology (P for trend=0.041). An age-specific decline in the overall high-risk HPV prevalence was reaffirmed, and the proportion of HPV52 declined markedly with age (P for trend=0.014). The type-specific prevalence of high-risk HPV types significantly varies according to cervical cytology and age. It may imply that these types have different to develop into precancerous lesions in normal cervix.

  3. Human Papillomavirus-Related Cancer Surveillance, Prevention, and Screening Among Transgender Men and Women: Neglected Populations at High Risk.

    PubMed

    Brown, Brandon; Poteat, Tonia; Marg, Logan; Galea, Jerome T

    2017-09-06

    Researchers and healthcare surveillance systems must clearly disaggregate data for transgender men and women from data for cisgender men and women to identify population-level health disparities and give every person an opportunity for cancer prevention. The limited human papillomavirus (HPV) vaccine recommendations for transgender men and women may be due to the scant literature on cancer prevalence coupled with poor understanding of HPV risks for these populations. Comprehensive cancer screening and prevention initiatives centered on relevant anatomy and sexual risk behaviors that are inclusive of transgender men and women are needed. Moreover, we need specific research to understand the impact of HPV and associated cancers on both transgender men's and women's lives.

  4. Associations between sexually transmitted infections, high-risk human papillomavirus infection, and abnormal cervical Pap smear results in OB/GYN outpatients.

    PubMed

    Kim, Hye Sun; Kim, Tae Jin; Lee, In Ho; Hong, Sung Ran

    2016-09-01

    This study aimed to examine the meaning and usefulness of sexually transmitted infection (STI) test when caring for patients who have abnormal cervical cytology and/or positive high-risk human papillomavirus (HPV) DNA test results. Among patients who underwent liquid-based cervical cytology and HPV DNA tests at the Obstetrics and Gynecology outpatient clinic, 800 patients who showed abnormal cervical cytology were compared with 200 patients in the control group. Both groups were simultaneously tested via multiplex real-time polymerase chain reaction for seven types of STI-causative microorganisms. The positive rate of high-risk HPV infection in total STIs positive group was 1.47 times higher than that of total STIs negative group. The probability of a cytological diagnosis of a grade equal to or higher than atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion (ASC-H) was significantly higher in patients testing positive for total STIs (1.46 times), Chlamydia trachomatis (3.21 times), or Mycoplasma genitalicum (3.58 times) than in those testing negative. The total STIs positive rate was significantly higher for those having a cytological diagnosis of a grade equal to or higher than atypical squamous cells of undetermined significance (ASC-US) when high-risk HPV test result was negative. Correlations were present not only between STIs and high-risk HPV infection but also between abnormal cervical cytology and STIs. Therefore, additional evaluation of STIs will be helpful to appropriately diagnose and treat patients with abnormal cervical cytology, positive results on high-risk HPV DNA test, or a cytological diagnosis of ASC-US despite negative high-risk HPV DNA test result.

  5. Detection of high-risk human papillomavirus type 16/18 in cutaneous warts in immunocompetent patients, using polymerase chain reaction.

    PubMed

    Payal, R; Gupta, S; Aggarwal, R; Handa, S; Radotra, B D; Arora, S K

    2006-10-31

    Cutaneous warts are caused by human papillomavirus (HPV). Prevalence studies of the types of HPV present in cutaneous warts have been carried out more frequently in immunosuppressed patients. The present study was designed to study the association of high-risk HPV in cutaneous warts of immunocompetent patients. A total of 45 cases of cutaneous warts from various sites in immunocompetent subjects were analyzed for HPV. Samples included both archival material i.e., paraffin embedded and fresh tissue. Highly sensitive and comprehensive polymerase chain reaction (PCR) methodology for detection of HPV of high oncogenic potential, HPV 16/18, was employed. Human papillomavirus 16 was detected in 3 (6.6%) patients. None of the lesions demonstrated HPV 18. None of the cutaneous warts demonstrated histopathological features associated with dysplasia or neoplasia. The identification of HPV 16 in cutaneous warts, which are benign proliferations of the skin, further expands the spectrum of HPV-linked lesions. It remains of critical interest to determine whether these types are specifically associated with the development of malignant lesions analogous to those seen in anogenital cancer.

  6. Consistent condom use reduces the genital human papillomavirus burden among high-risk men: the HPV infection in men study.

    PubMed

    Pierce Campbell, Christine M; Lin, Hui-Yi; Fulp, William; Papenfuss, Mary R; Salmerón, Jorge J; Quiterio, Manuel M; Lazcano-Ponce, Eduardo; Villa, Luisa L; Giuliano, Anna R

    2013-08-01

    Data supporting the efficacy of condoms against human papillomavirus (HPV) infection in males are limited. Therefore, we examined the effect of consistent condom use on genital HPV acquisition and duration of infection. A prospective analysis was conducted within the HPV Infection in Men Study, a multinational HPV cohort study. Men who were recently sexually active (n = 3323) were stratified on the basis of sexual risk behaviors and partnerships. Using Cox proportional hazards regression, type-specific incidence of HPV infection and clearance were modeled for each risk group to assess independent associations with condom use. The risk of HPV acquisition was 2-fold lower among men with no steady sex partner who always used condoms, compared with those who never used condoms (hazard ratio, 0.54), after adjustment for country, age, race, education duration, smoking, alcohol, and number of recent sex partners. The probability of clearing an oncogenic HPV infection was 30% higher among nonmonogamous men who always used condoms with nonsteady sex partners, compared with men who never used condoms (hazard ratio, 1.29), after adjustment for country, age, race, education duration, marital status, smoking, alcohol, and number of recent sex partners. No protective effects of condom use were observed among monogamous men. Condoms should be promoted in combination with HPV vaccination to prevent HPV infection in men.

  7. Identification of high-risk human papillomavirus (hrHPV)-associated genes in early stage cervical squamous cell carcinomas.

    PubMed

    Hu, Y; Liu, Y; Liu, C-B; Ling, Z-Q

    2011-01-01

    This retrospective study investigated gene expression in tumour samples from 38 patients with early stage human papillomavirus (HPV)-associated cervical squamous cell carcinoma (CSCC). The patients were divided into two groups based on the presence of viral markers of HPV16 or HPV18 infection. Gene expression profiles of tumour samples and the corresponding normal cervical epithelium were analysed using cDNA microarrays. Several genes showed differential expression between the two groups of HPV-infected CSCC patients, although seven genes showed similar changes in both groups. The four genes encoding cyclin-dependent kinase inhibitor 2A, matrix metallopeptidase 9, laminin γ-1, and epidermal growth factor receptor were up-regulated, and the three genes encoding transforming growth factor β receptor 1, interleukin-1α and insulin-like growth factor-binding protein 6 were down-regulated, in both HPV16(+) and HPV18(+) CSCC. These proteins are involved in cell proliferation, cell structure and cell attachment, so their expression might be involved in the mechanism of HPV-induced carcino genesis. A clearer understanding of HPV type-specific gene expression might aid diagnosis and treatment.

  8. 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.

  9. Incidence, Duration, Persistence, and Factors Associated With High-risk Anal Human Papillomavirus Persistence Among HIV-negative Men Who Have Sex With Men: A Multinational Study

    PubMed Central

    Nyitray, Alan G.; Carvalho da Silva, Roberto J.; Chang, Mihyun; Baggio, Maria Luiza; Ingles, Donna J.; Abrahamsen, Martha; Papenfuss, Mary; Lin, Hui-Yi; Salmerón, Jorge; Quiterio, Manuel; Lazcano-Ponce, Eduardo; Villa, Luisa L.; Giuliano, Anna R.

    2016-01-01

    Background. Given high rates of anal disease, we investigated the natural history of high-risk anal human papillomavirus (HPV) among a multinational group of men who have sex with men (MSM) aged 18–64 years. Methods. Anal specimens from human immunodeficiency virus–negative men from Brazil, Mexico, and the United States were genotyped. Over 2 years, 406 MSM provided evaluable specimens every 6 months for ≥2 visits. These men were stratified into men who have sex only with men (MSOM, n = 70) and men who have sex with women and men (MSWM, n = 336). Persistence was defined as ≥12 months’ type-specific duration and could begin with either a prevalent or incident infection. Prevalence ratios and 95% confidence intervals were calculated by Poisson regression. Results. Median follow-up time was 2.1 years. Retention was 82%. Annual cumulative incidence of 9-valent vaccine types was 19% and 8% among MSOM and MSWM, respectively (log-rank P = .02). Duration of anal HPV did not differ for MSOM and MSWM and was a median of 6.9 months for HPV-16 after combining men from the 2 groups. Among men with prevalent high-risk infection (n = 106), a total of 36.8%, retained the infection for at least 24 months. For those with prevalent HPV-16 (n = 27), 29.6% were persistent for at least 24 months. Persistence of high-risk HPV was associated with number of male anal sex partners and inversely associated with number of female sex partners. Conclusions. MSM with prevalent high-risk HPV infection should be considered at increased risk for nontransient infection. PMID:26962079

  10. Human papillomavirus (HPV) in Egyptian females: study by cytology, histopathology, colposcopy and molecular diagnosis of high risk types.

    PubMed

    Nayel, M A; Shaker, O G; Hosni, A N; Hosni, H N; Khalifa, S E; Shazly, A F

    2016-12-01

    In Northern Africa, the region Egypt belongs to, about 10.7% of women are estimated to harbour cervical human papillomavirus (HPV) infection and 78.4% of invasive cancers are attributed to HPVs 16 or 18. We aimed at comparing HPV detection by ISH-PCR tissue with other conventional available cheaper techniques, finding which of them can be relied upon in a developing country like Egypt for HPV detection. Sixty patients were included. For them colposcopy, PAP smear, histopathology and detection of HPV using ISH PCR tissue and PCR swab were achieved. PCR-ISH tissue was positive in 53.33%, 46.6% were negative. Pap smear was negative in 26 cases (43.33%) and 43 cases (56.67%) were positive. LSIL with perinuclear halo represented nearly half of the positive cases (16/34; 47.05%), 10 cases were diagnosed as HSIL, 4 cases as ASCUS and 4 as AGC. Histopathology was negative in 12 (20%) cases and 48 (80%) cases were positive. CIN I and CIN I+ koliocytosis represented half of the cases (30/60) and more than half of positive cases (30/48; 62.5%). Comparing the results of pap smear, histopathology, colposcopy and PCR swab with ISH PCR tissue, highly significant results were seen with sensitivity of 87.5%, 100%, 62.5% and 56.2% respectively but the specificity were 78.6%, 42.9%, 28.6% and 100% respectively. Conventional cytology and histopathology were sensitive tests for detection of HPV. This may help for early detection of cancer cervix in a developing country like Egypt. PCR swab showed the highest specificity and the lowest sensitivity.

  11. Update on the College of American Pathologists Experience With High-Risk Human Papillomavirus Proficiency Testing for Cytology.

    PubMed

    Ghofrani, Mohiedean; Zhao, Chengquan; Davey, Diane D; Fan, Fang; Husain, Mujtaba; Laser, Alice; Ocal, Idris T; Shen, Rulong Z; Goodrich, Kelly; Souers, Rhona J; Crothers, Barbara A

    2016-12-01

    - Since 2008, the College of American Pathologists has provided the human papillomavirus for cytology laboratories (CHPV) proficiency testing program to help laboratories meet the requirements of the Clinical Laboratory Improvement Amendments of 1988. - To provide an update on trends in proficiency testing performance in the College of American Pathologists CHPV program during the 4-year period from 2011 through 2014 and to compare those trends with the preceding first 3 years of the program. - Responses of laboratories participating in the CHPV program from 2011 through 2014 were analyzed using a nonlinear mixed model to compare different combinations of testing medium and platform. - In total, 818 laboratories participated in the CHPV program at least once during the 4 years, with participation increasing during the study period. Concordance of participant responses with the target result was more than 98% (38 280 of 38 892). Overall performance with all 3 testing media-ThinPrep (Hologic, Bedford, Massachusetts), SurePath (Becton, Dickinson and Company, Franklin Lakes, New Jersey), or Digene (Qiagen, Valencia, California)-was equivalent (P = .51), and all 4 US Food and Drug Administration (FDA)-approved platforms-Hybrid Capture 2 (Qiagen), Cervista (Hologic), Aptima (Hologic), and cobas (Roche Molecular Systems, Pleasanton, California)-outperformed laboratory-developed tests, unspecified commercial kits, and other (noncommercial) methods in ThinPrep medium (P < .001). However, certain off-label combinations of platform and medium, most notably Cervista with SurePath, demonstrated suboptimal performance (P < .001). - Laboratories demonstrated proficiency in using various combinations of testing media and platforms offered in the CHPV program, with statistically significant performance differences in certain combinations. These observations may be relevant in the current discussions about FDA oversight of laboratory-developed tests.

  12. Cytological Anal Squamous Intraepithelial Lesions Associated with Anal High-Risk Human Papillomavirus Infections among Men Who Have Sex with Men in Northern Thailand.

    PubMed

    Ruanpeng, Darin; Chariyalertsak, Suwat; Kaewpoowat, Quanhathai; Supindham, Taweewat; Settakorn, Jongkolnee; Sukpan, Kornkanok; Utaipat, Utaiwan; Miura, Toshiyuki; Kosashunhanan, Natthapol; Saokhieo, Pongpun; Songsupa, Radchanok; Wongthanee, Antika

    2016-01-01

    Anal cancer, one of human papillomavirus (HPV) related malignancies, has increased in recent decades, particularly among men who have sex with men (MSM) and HIV-infected (HIV+) persons. We aimed to explore the prevalence of anal squamous intraepithelial lesions (ASIL) using Papanicolau (Pap) screening among MSM in northern Thailand and its associated factors. Two hundreds MSM aged ≥18 years reporting receptive anal intercourse in the prior 6 months were recruited from July 2012 through January 2013. Medical history and behavioral data were collected by staff interview and computer-assisted self interview. Anal Pap smear, HPV genotyping, and HIV testing were performed. Two pathologists blinded to HPV and HIV status reported cytologic results by Bethesda classification. Mean age was 27.2 years (range 18-54). Overall, 86 (43.0%) had ASIL: 28 (14.2%) with atypical cells of undetermined significance (ASCUS), 1 (0.5%) with atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H), 56 (28.4%) with low-grade squamous intraepithelial lesion (LSIL), and 1 (0.5%) with high-grade squamous intraepithelial lesion (HSIL). ASIL was associated by univariate analysis (p ≤0.05) with older age, gender identity other than bisexual (i.e., gay men and transgender women), rectal douching, anal symptoms, genital warts, HIV positivity, and high-risk-HPV infection. However, on multiple logistic regression ASIL was associated only with high-risk HPV type (p = 0.002) and HIV infection (p = 0.01). ASIL is quite common in high-risk MSM in northern Thailand and is associated with high-risk HPV types and HIV infection. Routine anal Pap screening should be considered, given the high frequency of ASIL, particularly in the HIV+. High resolution anoscopy (HRA), not done here, should be to confirm PAP smears whose sensitivity and specificity are quite variable. Timely HPV vaccination should be considered for this population.

  13. Development of a Multiplex PCR Test with Automated Genotyping Targeting E7 for Detection of Six High-Risk Human Papillomaviruses.

    PubMed

    Paes, Eliana Ferreira; de Assis, Angela Maria; Teixeira, Cirbia S Campos; Aoki, Francisco Hideo; Teixeira, Julio Cesar

    2015-01-01

    Cervical cancer is caused by high-risk human papillomaviruses (HPV) and viral detection tests aid in the diagnosis of precursor lesions. In the present study, a molecular test for detection of high-risk HPV DNA, called E7-HPV, was standardized and assessed in samples from women with pre-cancerous lesions. The development of the E7-HPV test for detection and genotyping of six high-risk HPV (types 16, 18, 31, 33, 45 and 52), consisted of evaluating primer quality and adjusting the multiplex PCR conditions. Primer design was based on the E7 region of each HPV, and the fluorochrome 6-FAM was added to PCR primers. Viral detection was performed by capillary electrophoresis in automated sequencer in samples obtained from 60 women (55 with ASC-H/HSIL cytology) from August to September 2013. A non-inferiority analysis was conducted with the cobas HPV test as a reference and following international guidelines for the development of new tests. The two tests had a high concordance rate in HPV16 detection (kappa=0.972), with only one discordant case (cervical intraepithelial neoplasia grade 3, negative with cobas and positive for HPV16 by E7-HPV) and complete agreement in HPV18 detection. When comparing detection of all high-risk HPV, three cases were positive with cobas but negative with E7-HPV, and another three cases were negative with cobas but positive with E7-HPV (HPV16, 31 and 52). When we evaluate the cases initially suspected by cytology, the two tests had the same sensitivity in detection CIN2 or worse. In conclusion, the E7-HPV test has satisfactory initial results, and its development can be continued.

  14. Prevalence of high-risk human papillomavirus cervical infection in female kidney graft recipients: an observational study

    PubMed Central

    2012-01-01

    Background Immunosuppressive therapy protects the transplanted organ but predisposes the recipient to chronic infections and malignancies. Transplant patients are at risk of cervical intraepithelial neoplasia (CIN) and cervical cancer resulting from an impaired immune response in the case of primary infection or of reactivation of a latent infection with human papillomavirus of high oncogenic potential (HR-HPV). Methods The aim of this study was to assess the prevalence of HR-HPV cervical infections and CIN in 60 female kidney graft recipients of reproductive age in comparison to that in healthy controls. Cervical swabs were analyzed for the presence of HR-HPV DNA. HR-HPV-positive women remained under strict observation and were re-examined after 24 months for the presence of transforming HR-HPV infection by testing for HR-HPV E6/E7 mRNA. All the HR-HPV-positive patients were scheduled for further diagnostic tests including exfoliative cytology, colposcopy and cervical biopsy. Results The prevalence of HR-HPV did not differ significantly between the study group and the healthy controls (18% vs 25%, p = 0.37). There was no correlation between HR-HPV presence and the immunosuppresive regimen, underlying disease, graft function or time interval from transplantation. A higher prevalence of HR-HPV was observed in females who had had ≥2 sexual partners in the past. Among HR-HPV-positive patients, two cases of CIN2+ were diagnosed in each group. In the course of follow-up, transforming HR-HPV infections were detected in two kidney recipients and in one healthy female. Histologic examination confirmed another two cases of CIN2+ developing in the cervical canal. Conclusions Female kidney graft recipients of reproductive age are as exposed to HR-HPV infection as are healthy individuals. Tests detecting the presence of HR-HPV E6/E7 mRNA offer a novel diagnostic opportunity in those patients, especially in those cases where lesions have developed in the cervical canal

  15. Prevalence of high-risk human papillomavirus and cervical intraepithelial neoplasias in a previously unscreened population--a pooled analysis from three studies.

    PubMed

    Basu, Partha; Mittal, Srabani; Bhaumik, Suchismita; Mandal, Shyam Sunder; Samaddar, Anusree; Ray, Chinmayi; Siddiqi, Maqsood; Biswas, Jaydip; Sankaranarayanan, Rengaswamy

    2013-04-01

    Population prevalence of human papillomavirus (HPV) and cervical intraepithelial neoplasias (CIN) is an important indicator to judge the disease burden in the community, to monitor the performance of cervical cancer screening program and to assess the impact of HPV vaccination program. India being a country without any cervical cancer screening program has no published data on the population prevalence of CIN and only a few large community-based studies to report the high-risk HPV prevalence. The objective of our study was to study HPV and CIN prevalence in a previously unscreened population. We pooled together the results of three research studies originally designed to assess the performance of visual inspection after acetic acid application and Hybrid Capture 2 (HC 2). Nearly 60% of the screened women had colposcopy irrespective of their screening test results. The diagnosis and grading of cervical neoplasias were based on histology. The age standardized prevalence of HPV by HC 2 test was 6.0%. Age-adjusted prevalence of CIN1 and CIN2 was 2.3% and 0.5%, respectively. The age-adjusted prevalence of CIN3 was 0.4% and that of invasive cancer was 0.2%. The prevalence of high-risk HPV was relatively low in the population we studied, which is reflected in the low prevalence of high-grade CIN. The prevalence of CIN3 remained constant across age groups due to absence of screening. Copyright © 2012 UICC.

  16. Human papillomavirus and cervical cancer.

    PubMed

    Crosbie, Emma J; Einstein, Mark H; Franceschi, Silvia; Kitchener, Henry C

    2013-09-07

    Cervical cancer is caused by human papillomavirus infection. Most human papillomavirus infection is harmless and clears spontaneously but persistent infection with high-risk human papillomavirus (especially type 16) can cause cancer of the cervix, vulva, vagina, anus, penis, and oropharynx. The virus exclusively infects epithelium and produces new viral particles only in fully mature epithelial cells. Human papillomavirus disrupts normal cell-cycle control, promoting uncontrolled cell division and the accumulation of genetic damage. Two effective prophylactic vaccines composed of human papillomavirus type 16 and 18, and human papillomavirus type 16, 18, 6, and 11 virus-like particles have been introduced in many developed countries as a primary prevention strategy. Human papillomavirus testing is clinically valuable for secondary prevention in triaging low-grade cytology and as a test of cure after treatment. More sensitive than cytology, primary screening by human papillomavirus testing could enable screening intervals to be extended. If these prevention strategies can be implemented in developing countries, many thousands of lives could be saved.

  17. Isothermal Method of a Recombinase Polymerase Amplification Assay for the Detection of Most Common High-Risk Human Papillomavirus Type 16 and Type 18 DNA.

    PubMed

    Ma, Biao; Fang, Jiehong; Wang, Ye; He, Haizhen; Dai, Mingyan; Lin, Wei; Su, Wei; Zhang, Mingzhou

    2017-01-01

    Cervical cancer is a common gynecologic malignant tumor and has a great impact on women's health. Human papillomavirus (HPV) is implicated in cervical cancer and precancerous lesions and the two are possibly two stages of disease progression. With the technological development of molecular biology and epidemiology, detection and treatment of HPV has become an important means to prevent cervical cancer. Here we present a novel, rapid, sensitive and specific isothermal method of recombinase polymerase amplification (RPA), which is established to detect the two most common high-risk human papillomavirus type 16 and type 18 DNA. In this study, we evaluate the efficacy of the RPA assay, incubating clinical specimens of HPV16 and HPV18 using plasmids standard. It operates at constant low temperature without the thermal instrumentation for incubation. The products can be detected via agarose gel electrophoresis assay, reverse dot blot assay, and quantitative real-time assay with SYBR Green I. We assess the diagnostic performance of the RPA assay for detecting of HPV16 and HPV18 in 335 clinical samples from patients suspected of cervical cancer. The results revealed no cross-reaction with other HPV genotypes and the RPA assay achieve a sensitivity of 100 copies. Compared with TaqMan qPCR, the RPA technique achieves exponential amplification with no need for pretreatment of sample DNA at 37°C for 20 minutes, which reveals more satisfactory performance. The agreement between the RPA and qPCR assays was 97.6% (κ = 0.89) for HPV16 positivity and 98.5% (κ = 0.81) for HPV18 positivity, indicating very good correlation between both tests. Importantly, the RPA assay was demonstrated to be a useful and powerful method for detection of HPV virus, which therefore may serve as a valuable tool for rapid diagnosis of HPV infection in both commercial and clinical applications.

  18. Influence of age and geographical origin in the prevalence of high risk human papillomavirus in migrant female sex workers in Spain

    PubMed Central

    del Amo, J; Gonzalez, C; Losana, J; Clavo, P; Munoz, L; Ballesteros, J; Garcia-Saiz, A; Belza, M; Ortiz, M; Menendez, B; del Romero, J; Bolumar, F

    2005-01-01

    Objectives: To estimate the prevalence and risk factors of high risk human papillomavirus (HPV) infection in migrant female sex workers (FSW) according to age and geographical origin. Methods: Cross sectional study of migrant FSW attending a sexually transmitted infection (STI) clinic in Madrid during 2002. Information on sociodemographic characteristics, reproductive and sexual health, smoking, time in commercial sex work, history of STIs, HIV, hepatitis B, hepatitis C, syphilis, and genitourinary infections was collected. High risk HPV Infection was determined through the Digene HPV Test, Hybrid Capture II. Data were analysed through multiple logistic regression. Results: 734 women were studied. Overall HPV prevalence was 39%; 61% in eastern Europeans, 42% in Ecuadorians, 39% in Colombians, 29% in sub-Saharan Africans, and 24% in Caribbeans (p = 0.057). HPV prevalence showed a decreasing trend by age; 49% under 20 years, 35% in 21–25 years,14% over 36 years% (p<0.005). In multivariate analyses, area of origin (p = 0.07), hormonal contraception in women not using condoms (OR 19.45 95% CI: 2.45 to 154.27), smoking, age, and an interaction between these last two variables (p = 0.039) had statistically significant associations with HPV prevalence. STI prevalence was 11% and was not related to age or geographical origin. Conclusions: High risk HPV prevalence in migrant FSW is elevated and related to age, area of origin, and use of oral contraceptives in women not using condoms. These data support the role of acquired immunity in the epidemiology of HPV infection and identifies migrant FSW as a priority group for sexual health promotion. PMID:15681729

  19. Prevalence of anal infection due to high-risk human papillomavirus and analysis of E2 gene integrity among women with cervical abnormalities.

    PubMed

    Gonzalez-Losa, María Del Refugio; Puerto-Solís, Marylin; Ayora-Talavera, Guadalupe; Gómez-Carvallo, Jesús; Euán-López, Alejandra; Cisneros-Cutz, José I; Rosado-López, Ariel; Echeverría Salazar, Jesúa; Conde-Ferráez, Laura

    2017-01-06

    High-risk human papillomaviruses (HR-HPV) infection has been associated with 90% of anal cancer cases. Women with abnormal cytology are a high-risk group to develop anal neoplasia. The aim of this study is to describe the prevalence and epidemiology of HR-HPV 16, 18, 45, and 58 anal infections in women with cervical abnormalities, as well as to assess E2 gene integrity. A cross-sectional study was performed on 311 cervical and 311 anal samples from patients with abnormal cytology in two colposcopy clinics in Yucatan, Mexico. A specific PCR for oncogenes was performed in order to identify HVP 16, 18, 45 and 58. Real time PCR was used to amplify the whole HPV 16, 18, and 58 E2 gene to verify its integrity in anal samples. High risk HPV 16, 18, 58, and/or 45 were found in 41.47% (129/311) of cervical samples, and in 30.8% (96/331) of anal samples, with 18% (57/311) of the patients being positive in both samples. The same genotypes in both anatomical sites were observed in 11.25% (35/311). The E2 gene was disrupted in 82% of all tested samples. The frequency of genome disruption viral integration in anal samples by genotype was: HPV 58 (97.2%); HPV 16 (72.4%), and HPV 18 (0%). Women with cervical disease have HR-HPV anal infections, and most of them have the E2 gene disrupted, which represents a risk to develop anal cancer. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  20. The effect of single nucleotide polymorphisms in G-rich regions of high-risk human papillomaviruses on structural diversity of DNA.

    PubMed

    Marušič, Maja; Hošnjak, Lea; Krafčikova, Petra; Poljak, Mario; Viglasky, Viktor; Plavec, Janez

    2017-05-01

    Infection with high-risk human papillomaviruses (HPVs) can lead to development of cancer of the head and neck and anogenital regions. G-rich sequences found in genomes of high-risk HPVs can fold into non-canonical secondary structures that could serve as 3D motifs distinct from double-stranded DNA and present recognition sites for ligands and opportunity for gene expression modulation. Combination of UV, CD and NMR spectroscopy and PAGE electrophoresis were used as they offer complementary insights into structural changes of G-rich oligonucleotides. G-rich region of HPV16 is shown to preferentially form hairpin structures, while regions of HPV18, HPV52 and HPV58 fold into four-stranded DNA structures called G-quadruplexes. Single nucleotide polymorphisms found in G-rich sequences have been found to promote formation of hairpin structures of HPV16 and have affected number of species formed in G-rich region of HPV52, whereas they have exhibited minimal effect on the formation of HPV18 and HPV58 G-quadruplex structures. These structural changes were reflected in differences in apparent thermal stabilities. Potential of G-rich sequences as drug targets was evaluated based on the results of the current study. HPV16 and HPV18 are considered less appropriate targets due to several single nucleotide polymorphisms and low stability, respectively. On the other hand, HPV52 and HPV58 could be used for small-molecule mediated stabilization. G-rich sequences occurring in high-risk HPVs can fold into hairpin and G-quadruplex structures that could be potentially utilized as drug targets. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. [Prevalence of non-vaccinable high risk genotypes of human papillomavirus in the Early Detection of Cervical Cancer Program in Cantabria].

    PubMed

    Paz-Zulueta, María; Fernández-Feito, Ana; Amparán Ruiz, Marina; Azofra Olave, Asunción; Martín Seco, Yolanda; Ojugas Zabala, Sonia; Otero García, Aurora; Royano Rasines, Carmen; Sarabia-Lavín, Raquel; Torres Manrique, Blanca; Santibáñez Margüello, Miguel

    2016-01-01

    To estimate the prevalence of infection with non-vaccinable high risk genotypes of human papillomavirus (HPV). Cross-sectional study. Seven randomly selected health centres in Cantabria (Northern Spain). All women with an evaluable vaginal smear (n=3,359) between 2010 and 2011. The variables collected were cytological diagnosis, PCR results, and family planning method. The vaginal smear results were classified with the Bethesda system. The classification by Muñoz et al. was used for typing as oncogenic risk HPV. Proportions and odds ratio (OR) were estimated with corresponding confidence intervals at 95% (95% CI). The prevalence of HPV infection was 2.71% (95% CI: 2.15 to 3.27). The prevalence of high oncogenic risk HPV genotypes was 2.26%; (95% CI: 1.75 to 2.78). The most frequent genotype was 16 (28.89%). More than half of the women were positive for one of the non-vaccinable high risk genotypes: 51 (18.89%) and 58 (13.33%) and 68 (12.22%) or 31 (11.11%). At least two non-vaccinable high-risk genotypes co-existed in 23.33% of women. Younger women (≤30 years) had twice the risk of any HPV infection: OR 2.01 (95% CI: 1.02 to 3.96); and were twice as likely to use condoms compared to hormonal contraceptives, OR 2.09 (95% CI: 1.64 to 2.67). According to the high percentage of non-vaccinable high oncogenic risk HPV types, there should be a re-think of the prevention strategy in the population, who may have a false sense of protection. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  2. Prevalence of high-risk human papillomavirus and abnormal pap smears in female sex workers compared to the general population in Antwerp, Belgium.

    PubMed

    Vorsters, Alex; Cornelissen, Tine; Leuridan, Elke; Bogers, Johannes; Vanden Broeck, Davy; Benoy, Ina; Goossens, Herman; Hens, Niel; Van Damme, Pierre

    2016-06-07

    Although female sex workers (FSWs) are a well-known high-risk group for Human Papillomavirus (HPV) infections, few tailored intervention programmes for HPV have been established worldwide. The lack of reliable data on the prevalence of HPV and related cervical lesions hampers the establishment of evidence-based intervention programmes. The objectives of this study were to describe the prevalence of high-risk Human Papillomavirus (hrHPV) infections and abnormal pap smears in FSWs compared to a control group in Antwerp, Belgium. HPV genotyping and cytology data were analysed from routine Pap smear tests that were collected from both FSWs and the general population (1334 samples for each group) between June 2006 and June 2010. Within the laboratory database, all FSWs were matched 1:1 for age and testing date to determine the ORs of hrHPV genotypes, DNA and cytology outcome. The prevalence of hrHPV DNA in FSWs was 41.7 % compared to 19.8 % in the age-matched controls with an overall OR of 2.8 (95 % CI: 2.3-3.4). Significant differences were observed in all age groups, and the most significant differences were observed in the cohort under 21 years of age (prevalence of 64.4 % in FSWs versus 14.8 % in controls; OR 10.3 (95 % CI: 5.0-21.2). Significantly more cervical lesions were observed in FSWs, particularly in the 17- to 21-year old age group (OR for LSIL or HSIL: 10.3 (95 % CI: 3.2-33.8). In both groups, HPV 16 was the most prevalent at 12.1 and 6.6 % in the FSW and control groups, respectively. HPV 18 was the 8(th) and 7(th) most frequent genotype at 5.0 and 2.5 % in the FSW and control groups, respectively. FSWs have a significantly higher prevalence of hrHPV and more abnormal Pap smears than does the general population in Antwerp, Belgium. The hrHPV prevalence in FSWs is similar to that reported in the literature. The need for tailored intervention programmes should be investigated further.

  3. What drives the number of high-risk human papillomavirus types in the anal canal in HIV-positive men who have sex with men?

    PubMed

    del Amo, Julia; González, Cristina; Geskus, Ronald B; Torres, Montse; Del Romero, Jorge; Viciana, Pompeyo; Masiá, Mar; Blanco, Jose R; Hernández-Novoa, Beatriz; Ortiz, Marta

    2013-04-15

    We estimated the effect of sexual behavior, age, and immunodeficiency on the number of high-risk human papillomavirus (HR-HPV) types in the anal canal among human immunodeficiency virus-positive men who have sex with men (MSM). Anal samples were genotyped with the Linear Array HPV Genotyping Test, and risk factors were investigated with Poisson regression. Of 586 MSM, 69% were Spanish, and 25.6% were Latin American; the median age was 34.9 years (interquartile range [IQR], 30.1-40.8). The median number of recent sex partners was 6 (IQR, 2-24 sex partners), and the median CD4(+) T-cell count was 531.5 cells/mm(3) (IQR, 403-701 cells/mm(3)). The prevalence of any and multiple HR-HPV infections was 83.4% and 60.5%, respectively. The most common types were HPV-16 (42%), HPV-51 (24%), HPV-39 (23.7%), and HPV-59 (23.5%). Age had a statistically significant, nonlinear association with the number of types, with the highest number detected around 35 years of age (P < .001). The number of recent sex partners had a statistically significant, fairly linear association on the log scale (P = .033). The high prevalence of HR-HPV types is associated with recent sexual behavior and age.

  4. 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 ...

  5. HPV (Human Papillomavirus)

    MedlinePlus

    ... For Consumers Consumer Information by Audience For Women HPV (human papillomavirus) Share Tweet Linkedin Pin it More ... outside of the body. To Learn More About HPV Human Papillomavirus Vaccine More in For Women Medication ...

  6. Cost-effectiveness analysis of cervical cancer prevention based on a rapid human papillomavirus screening test in a high-risk region of China.

    PubMed

    Levin, Carol E; Sellors, John; Shi, Ju-Fang; Ma, Li; Qiao, You-lin; Ortendahl, Jesse; O'Shea, Meredith K H; Goldie, Sue J

    2010-09-01

    This study assessed the cost-effectiveness of a new, rapid human papillomavirus (HPV)-DNA screening test for cervical cancer prevention in the high-risk region of Shanxi, China. Using micro-costing methods, we estimated the resources needed to implement preventive strategies using cervical cytology or HPV-DNA testing, including the Hybrid Capture 2 (hc2) test (QIAGEN Corp., Gaithersburg, MD) and the rapid HPV-DNA careHPV test (QIAGEN). Data were used in a previously published model and empirically calibrated to country-specific epidemiological data. Strategies differed by initial test, targeted age, frequency of screening, number of clinic visits required (1, 2 or 3) and service delivery setting (national, county and township levels). Outcomes included lifetime risk of cancer, years of life saved (YLS), lifetime costs and incremental cost-effectiveness ratios (cost per YLS). For all screening frequencies, the most efficient strategy used 2-visit rapid HPV-DNA testing at the county level, including screening and diagnostics in the first visit, and treatment in the second visit. Screening at ages 35, 40 and 45 reduced cancer risk by 50% among women compliant with all 3 screening rounds, and was US$ 150 per YLS, compared with this same strategy applied twice per lifetime. This would be considered very cost-effective evaluated against China's per-capita gross domestic product (US$ 1,702). By enhancing the linkage between screening and treatment through a reduced number of visits, rapid HPV-DNA testing 3 times per lifetime is more effective than traditional cytology, and is likely to be cost-effective in high-risk regions of China.

  7. Verrucous carcinomas of the head and neck, including those with associated squamous cell carcinoma, lack transcriptionally active high-risk human papillomavirus.

    PubMed

    Patel, Kalyani R; Chernock, Rebecca D; Zhang, Tian R; Wang, Xiaowei; El-Mofty, Samir K; Lewis, James S

    2013-11-01

    Most oropharyngeal squamous cell carcinomas (SCC) and histologic variants harbor transcriptionally active human papillomavirus (HPV). While HPV DNA can be found in many non-oropharyngeal head and neck carcinomas, transcriptionally active HPV is rare. Verrucous carcinoma is a variant with bland cytology, warty appearance, locally destructive growth, and lack of metastasis when lacking a frankly invasive carcinoma component. Studies have shown variable rates of HPV DNA and p16 protein expression in such tumors but still have not clearly addressed if the virus has biological activity or clinical relevance in the positive cases. Department files were searched for verrucous neoplasms, including pure verrucous carcinoma, verrucous carcinoma with dysplasia or minimal invasion, and SCC arising in verrucous carcinoma (ie, having a major component of frankly invasive carcinoma). p16 immunohistochemistry, HPV DNA polymerase chain reaction (PCR) and E6/E7 mRNA reverse transcription PCR for high-risk HPV types were performed. Of the 49 cases, 6 (12.2%) showed strong (>50%) staining for p16. HPV DNA was detected in 7/49 (14.3%) cases, but only one case was positive for both p16, and HPV DNA. A total of 36 cases yielded sufficient RNA for RT-PCR (18 verrucous carcinomas, 13 atypical verrucous carcinomas, and 5 SCC arising in verrucous carcinoma). All 36 were negative, including the four p16-positive and three HPV DNA-positive tumors tested. Although a minority of verrucous carcinoma lesions are p16 and HPV DNA positive, transcriptionally active high-risk HPV is uniformly absent. These findings argue that verrucous carcinoma and its related squamous cell carcinomas are not HPV-driven tumors. © 2013.

  8. Efficacy of an HIV intervention in reducing high-risk human papillomavirus, nonviral sexually transmitted infections, and concurrency among African American women: a randomized-controlled trial.

    PubMed

    Wingood, Gina M; Diclemente, Ralph J; Robinson-Simpson, Lashun; Lang, Delia L; Caliendo, Angela; Hardin, James W

    2013-06-01

    This trial evaluated the efficacy of an HIV-intervention condition, relative to a health-promotion condition, in reducing incidence of nonviral sexually transmitted infections (STIs; Chlamydia, gonorrhea, and trichomoniasis), oncogenic human papillomavirus (HPV) subtypes 16 and 18, sexual concurrency, and other HIV-associated behaviors over a 12-month period. Randomized-controlled trial. Data analysts blinded to treatment allocation. Kaiser Permanente, GA. A random sample of 848 African American women. The two 4-hour HIV intervention sessions were based on Social Cognitive Theory and the Theory of Gender and Power. The intervention was designed to enhance participants' self-sufficiency and attitudes and skills associated with condom use. The HIV intervention also encouraged STI testing and treatment of male sex partners and reducing vaginal douching and individual and male partner concurrency. Incident nonviral STIs. In generalized estimating equations' analyses, over the 12-month follow-up, participants in the HIV intervention, relative to the comparison, were less likely to have nonviral incident STIs (odds ratio [OR] = 0.62; 95% confidence interval [CI]: 0.40 to 0.96; P = 0.033) and incident high-risk HPV infection (OR = 0.37; 95% CI: 0.18 to 0.77; P = 0.008) or concurrent male sex partners (OR = 0.55; 95% CI: 0.37 to 0.83; P = 0.005). In addition, intervention participants were less likely to report multiple male sex partners, more likely to use condoms during oral sex, more likely to inform their main partner of their STI test results, encourage their main partner to seek STI testing, report that their main partner was treated for STIs, and report not douching. This is the first trial to demonstrate that an HIV intervention can achieve reductions in nonviral STIs, high-risk HPV, and individual concurrency.

  9. High-risk human papillomavirus DNA test: could it be useful in low-grade cervical lesion triage? Five-year follow-up.

    PubMed

    Saccardi, Carlo; Gizzo, Salvatore; Noventa, Marco; Anis, Omar; Di Gangi, Stefania; Patrelli, Tito Silvio; D'Antona, Donato; Nardelli, Giovanni Battista

    2014-02-01

    We conducted a retrospective, observational study in order to evaluate the role of high-risk human papillomavirus (hrHPV)-DNA test in patients with first diagnosis of low-grade squamous intraepithelial lesions (L-SILs).Patients were divided into group A, annual Papanicolaou test and hrHPV-DNA tests (167 patients) and group B, immediate colposcopy, followed by annual papanicolaou test and hrHPV-DNA tests (164 patients). We assessed sensitivity, specificity, negative predictive value (NPV), positive predictive value, positive-negative likelihood ratio of hrHPV-DNA test, and 5-year relative risk of cervical intraepithelial neoplasia grade 2 in hrHPV-DNA+. Colposcopy is still considered the best choice for women with L-SIL and hrHPV-DNA+ test. High sensitivity and NPV of hrHPV-DNA test permit to use it in the follow-up of L-SIL with a HPV-negative status, without necessity of referring to colposcopy.

  10. Primary cervical cancer truly negative for high-risk human papillomavirus is a rare but distinct entity that can affect virgins and young adolescents.

    PubMed

    Liebrich, C; Brummer, O; Von Wasielewski, R; Wegener, G; Meijer, C; Iftner, T; Petry, K U

    2009-01-01

    Cancer of the uterine cervix is almost exclusively associated with human papillomavirus (HPV). Carcinogenesis is slow, the minimal time from initial HPV infection to invasive carcinoma seems to be less than ten years. In order to identify rapid onset cervical cancer, we carried out a retrospective re-analysis of an extended cohort of patients with invasive cervical cancer, and reviewed cases identified within the cancer registry of Lower Saxony or using Medline or ISI data. No instances of a rapid-onset cancer or true HPV-DNA negative cancer were found among our hospital cohort of 178 women with primary cancer of the uterine cervix. Registry data identified four out of 5,878 patients who were diagnosed with primary cervical cancer at 14 to 20 years of age. They were classified as clear-cell and endometriod adenocarcinoma and tested persistently negative for high-risk HPV-DNA. Fourteen more cases of cervical cancer in virgins and very young women were identified by a Medline search, mostly with unknown histologic type or rare subtypes of adenocarcinoma. In conclusion, rare adenocarcinoma of the uterine cervix may represent an entity unrelated to HPV, thus explaining instances of rapid onset cervical cancer.

  11. Results of a Health Education Message Intervention on HPV Knowledge and Receipt of Follow-up Care among Latinas Infected with High-risk Human Papillomavirus.

    PubMed

    Sanderson, Maureen; Khabele, Dineo; Brown, Claudine L; Harbi, Khalil; Alexander, Leah R; Coker, Ann L; Fernandez, Maria E; Brandt, Heather M; Fadden, Mary K; Hull, Pamela C

    2015-11-01

    A clinic-based intervention study was conducted among high-risk human papillomavirus (HPV)-infected Latinas aged 18-64 years between April 2006 and May 2008 on the Texas-Mexico border. Women were randomly assigned to receive a printed material intervention (n=186) or usual care (n=187) and were followed at three months, six months, and 12 months through telephone surveys and review of medical records. The HPV knowledge of nearly all women had increased greatly, but only two-thirds of women reported they had received follow-up care within one year of diagnosis regardless of additional health education messaging. Our findings suggest that, regardless of type of health education messaging, Latinas living on the Texas-Mexico border are aware that follow-up care is recommended, but they may not receive this care. Individual, familial and medical care barriers to receipt of follow-up care may partially account for the higher rates of cervical cancer mortality in this region.

  12. Competing-risks regression models in analysis of biomarkers as predictors of high-risk human papillomavirus (HPV) infection outcomes and incident CIN in the LAMS cohort.

    PubMed

    Syrjänen, Stina; Longhato-Filho, Adhemar; Sarian, Luis O; Naud, Paulo; Derchain, Sophie; Rottelli-Martins, Cecilia; Tatti, Silvio; Branca, Margherita; Eržen, Mojca; Hammes, Luciano S; Matos, Jean; Gontijo, Renata; Bragança, Joana; Arlindo, Francisco C; Maeda, Mariana Y S; Costa, Silvano; Syrjänen, Kari

    2013-07-01

    To assess the prediction potential of a 5-biomarker panel for detecting high-risk human papillomavirus (HR-HPV) infections and/or cervical intraepithelial neoplasia (CIN) progression. Five biomarkers, lipocalin, plasminogen activator inhibitor-2, p300, interleukin-10, and stratifin, were assessed in cervical biopsies from 225 women of the Latin American Screening Study. Competing-risks regression models were constructed to assess their predictive power for (i) HR-HPV outcomes (negative, transient, or persistent infection) and (ii) CIN outcomes (no progression, incident CIN1, CIN2, or CIN3). p300, LCN2, stratifin were significantly associated with prevalent HR-HPV but lost their significance in multivariate analysis. In the multivariate model, only p300 was an independent predictor of CIN3 (odds ratio=2.63; 95% confidence interval, 1.05-6.61; P=0.039). In univariate competing-risks regression, lipocalin predicted permanent HR-HPV-negative status, but in the multivariate model, IL-10 emerged as a independent predictor of HPV-negative status (subhazard ratio=4.04; 95% confidence interval, 1.81-9.01; P=0.001). The clinical value of the panel in predicting longitudinal outcomes of HR-HPV infection and/or incident CIN is limited.

  13. Prevalence of High-Risk Genotypes of Human Papillomavirus: Women Diagnosed with Premalignant and Malignant Pap Smear Tests in Southern Ecuador

    PubMed Central

    Loján González, Cisne; Córdova Rodríguez, Ana; Acurio Páez, Katherine; Arévalo, Ana Paulina; Bobokova, Jana

    2017-01-01

    Human papillomavirus (HPV) is the primary infectious agent for the development of cervical cancer, although the presence of the virus alone is insufficient for viral development and proliferation; this can be attributed to the increase in potential oncogenic risk, along with other risk factors. In the present investigation, the prevalence of high-risk HPV was determined from samples of premalignant or malignant cervical cytology in women from the southern region of Ecuador. The kit we used was able to detect genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. In addition, 64.5% of the analyzed samples were positive for HPV, with genotypes 16 and 18 being the most prevalent (16 was detected in 148 samples and 18 in 108). Genotypes 58 and 51 were the third most frequent simple and multiple infections, respectively. The data are very similar to those obtained worldwide, suggesting that the strategy of sex education, and the use of vaccines as primary prevention agents, could significantly decrease the incidence and mortality rate of cervical cancer in the southern region of Ecuador. PMID:28717342

  14. RNA Chromogenic in situ Hybridization Assay with Clinical Automated Platform is a Sensitive Method in Detecting High-risk Human Papillomavirus in Squamous Cell Carcinoma.

    PubMed

    Mendez-Pena, Javier E; Sadow, Peter M; Nose, Vania; Hoang, Mai P

    2017-03-13

    Detection of active human papillomavirus (HPV) is clinically important, as its presence has been shown to correlate with favorable clinical outcomes and better response to treatment in oropharyngeal squamous cell carcinomas (SCC). Using a clinical automated platform, we compared the performance of commercially available HPV DNA and RNA in situ hybridization (ISH) probes in archival tissues of 57 SCC. Importantly, a clinical automated platform gives 1) consistent and reproducible results for HPV ISH and 2) better standardization across clinical laboratories. Compared to polymerase chain reaction (PCR) results, RNA ISH exhibited 93% concordance versus 81% of DNA ISH. RNA ISH was more sensitive than DNA ISH (100% versus 88%), and more specific (87% versus 74%). When only accounting for 2-3+ positivity, sensitivity was 92% for RNA ISH versus 73% for DNA ISH, highlighting the ease of interpretation. p16 exhibited 96% sensitivity while specificity was only 55%. In 3 cases both RNA and DNA ISH were positive while PCR results were negative, suggesting that ISH methods might be a more sensitive method. Performing on a clinical automated platform, RNA ISH is sensitive in determining high-risk HPV status in formalin-fixed paraffin-embedded tissues and has the potential of being a standalone clinical test.

  15. High risk human papillomavirus testing: guidelines for use in screening, triage, and follow-up for the prevention and early detection of cervical cancer.

    PubMed

    Moore, Kathleen N; Walker, Joan L

    2004-11-01

    The changes in cervical cytology characterization agreed on by the Bethesda committee meeting in 2001 created a category of atypical findings that has caused some management confusion. By description, the characterization of cervical cytology as only atypical implies a less worrisome prognosis. However, more than 40% of high-grade (CIN II or III or cancer) will be discovered within this category. The development and Food and Drug Administration approval of the Hybrid Capture 2 (HC-2; Digene Corporation, Gaithersburg, MD) for detecting high-risk human papillomavirus (HR-HPV) subtypes and the subsequent level I evidence supporting use of this test in the triage of women with atypical cytology has revolutionized the management of this cytology. With this success has come numerous additional uses for HR-HPV testing in the treatment and follow-up of women with a variety of cytologic abnormalities. This article reviews the literature on uses of HR-HPV testing in this population, with reference to currently accepted guidelines.

  16. miR-1 inhibits progression of high-risk papillomavirus-associated human cervical cancer by targeting G6PD

    PubMed Central

    Liu, Guang-Cai; Hong, Ying; Chen, Hong-Lan; Kong, Shu-Yi; Huang, Yan-Mei; Xiyang, Yan-Bin; Jin, Hua

    2016-01-01

    Ectopic glucose-6-phosphate dehydrogenase (G6PD) expression may contribute to tumorigenesis in cervical cancer associated with high-risk human papillomavirus (HR-HPV 16 and 18) infections. Here, we demonstrate that microRNA-1 (miR-1) in association with AGO proteins targets G6PD in HR-HPV-infected human cervical cancer cells. miR-1 inhibited expression of a reporter construct containing a putative G6PD 3′-UTR seed region and suppressed endogenous G6PD expression. Down-regulation of miR-1 increased G6PD expression in cervical cancer cells. Regression analysis revealed that miR-1 levels correlate negatively with the clinicopathologic features in HR-HPV 16/18-infected cervical cancer patients. miR-1 overexpression inhibited proliferation and promoted apoptosis in cervical cancer cells and reduced xenograft tumor growth in nude mice. Conversely, sponge-mediated miR-1 knockdown markedly increased viability and reduced apoptosis in cervical cancer cells and supported neoplasm growth. Restoration of G6PD expression partially reversed the effects of miR-1 overexpression both in vitro and in vivo. In addition, co-transfection of G6PD siRNA and miR-1 sponge partially reversed miR-1 sponge-induced reductions in cell viability and neoplasm growth. These results suggest that miR-1 suppresses the development and progression of HR-HPV 16/18-infected cervical cancer by targeting G6PD and may be a promising novel therapeutic candidate. PMID:27861141

  17. Elevated glucose-6-phosphate dehydrogenase expression in the cervical cancer cases is associated with the cancerigenic event of high-risk human papillomaviruses

    PubMed Central

    Hu, Tao; Li, Ya-Shan; Chen, Bo; Chang, Ye-Fei; Liu, Guang-Cai; Hong, Ying; Chen, Hong-Lan

    2015-01-01

    The most important etiologic agent in the pathogenesis of cervical cancers (CCs) is human papillomavirus (HPV), while the mechanisms underlying are still not well known. Glucose-6-phosphate dehydrogenase (G6PD) is reported to elevate in various tumor cells. However, no available references elucidated the correlation between the levels of G6PD and HPV-infected CC until now. In the present study, we explored the possible role of G6PD in the pathology of CC induced by HPV infection. Totally 48 patients with HPV + CC and another 63 healthy women enrolled in the clinical were employed in the present study. Overall, prevalence of cervical infection with high-risk-HPV (HR-HPV) type examined was HPV-16, followed by HPV-18. The expressions of G6PD in CC samples were also detected by immunohistochemistry (IHC), qRT-PCR, and Western blot. Regression analysis showed elevated G6PD level was positively correlated with the CC development in 30–40 aged patients with HR-HPV-16/18 infection. The HPV16 + Siha, HPV18 + Hela, and HPV-C33A cell lines were employed and transfected with G6PD deficient vectors developed in vitro. MTT and flow cytometry were also employed to determine the survival and apoptosis of CC cells after G6PD expressional inhibition. Our data revealed that G6PD down-regulation induced poor proliferation and more apoptosis of HPV18 + Hela cells, when compared with that of HPV16 + Siha and HPV-C33A cells. These findings suggest that G6PD expressions in the HR-HPV + human CC tissues and cell lines play an important role in tumor growth and proliferation. PMID:25616277

  18. miR-1 inhibits progression of high-risk papillomavirus-associated human cervical cancer by targeting G6PD.

    PubMed

    Hu, Tao; Chang, Ye-Fei; Xiao, Zhangang; Mao, Rui; Tong, Jun; Chen, Bo; Liu, Guang-Cai; Hong, Ying; Chen, Hong-Lan; Kong, Shu-Yi; Huang, Yan-Mei; Xiyang, Yan-Bin; Jin, Hua

    2016-12-27

    Ectopic glucose-6-phosphate dehydrogenase (G6PD) expression may contribute to tumorigenesis in cervical cancer associated with high-risk human papillomavirus (HR-HPV 16 and 18) infections. Here, we demonstrate that microRNA-1 (miR-1) in association with AGO proteins targets G6PD in HR-HPV-infected human cervical cancer cells. miR-1 inhibited expression of a reporter construct containing a putative G6PD 3'-UTR seed region and suppressed endogenous G6PD expression. Down-regulation of miR-1 increased G6PD expression in cervical cancer cells. Regression analysis revealed that miR-1 levels correlate negatively with the clinicopathologic features in HR-HPV 16/18-infected cervical cancer patients. miR-1 overexpression inhibited proliferation and promoted apoptosis in cervical cancer cells and reduced xenograft tumor growth in nude mice. Conversely, sponge-mediated miR-1 knockdown markedly increased viability and reduced apoptosis in cervical cancer cells and supported neoplasm growth. Restoration of G6PD expression partially reversed the effects of miR-1 overexpression both in vitro and in vivo. In addition, co-transfection of G6PD siRNA and miR-1 sponge partially reversed miR-1 sponge-induced reductions in cell viability and neoplasm growth. These results suggest that miR-1 suppresses the development and progression of HR-HPV 16/18-infected cervical cancer by targeting G6PD and may be a promising novel therapeutic candidate.

  19. Expression of P16 in high-risk human papillomavirus related lesions of the uterine cervix in a government hospital, Malaysia.

    PubMed

    Krishnappa, Purushotham; Mohamad, Ibtisam Binti; Lin, Yip Jo; Barua, Ankur

    2014-11-01

    Cervical cancer is one of the most common cancers affecting women worldwide. It is well established that human papilloma virus (HPV) infection is the prime risk factor in the development of cervical cancer. The current screening and diagnostic tests have limitations in identifying the range of lesions caused by HPV. The current study aims to evaluate the diagnostic value of p16 immunohistochemical (IHC) investigation in high-risk human papillomavirus (HR-HPV) related lesions of the uterine cervix in Hospital Tuanku Jaafar, Seremban, Malaysia. A total of 75 cases were selected from the records of Pathology services, Hospital Tuanku Ja'afar, Seremban. The samples were collected in three separate groups (n=25 per group) as Carcinoma cervix, Carcinoma in situ and Chronic cervicitis. The demographic data of the patients and the representative paraffin blocks were retrieved from Hospital Tuanku Ja'afar, Seremban. The immunohistochemical staining with p16 and HPV 16 L1 were done on all cases. The staining intensity and density were observed and compared among the three groups of cases. Immunohistochemistry of p16INK4A staining shows nil (0/25) expression in the cervicitis patients, 72% (18/25) in CIN patients and 100% (25/25) in cervical carcinoma. HPV 16 L1 was positive in 100% (25/25) of cervicitis patients, 96% (24/25) of CIN patients and 40% (10/25) of cervical cancers patients. A chi square test was used to analyze the result and the obtained p value was <0.05. p16 expression was strongly observed in cervical cancer and minimally observed in cervicitis. Thus indicating p16 immunohistochemistry investigations can aid in diagnosing the different categories of cervical lesions into benign, insitu and malignant. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_202.

  20. Assessing the role of education in women's knowledge and acceptance of adjunct high-risk human Papillomavirus testing for cervical cancer screening.

    PubMed

    Papa, Debra; Moore Simas, Tiffany A; Reynolds, Megan; Melnitsky, Hannah

    2009-04-01

    To assess women's knowledge, concerns, and willingness for adjunct high-risk human papillomavirus (HR-HPV) testing before and after an educational intervention. At the time of their annual gynecologic examination, women aged 30 years and older received an educational intervention about HR-HPV. Subjects completed preintervention and postintervention questionnaires. Demographic characteristics were summarized using frequency measures. Comparisons between the pre-education and posteducation questionnaires were performed using Fisher exact test. Fifty women completed the study. After the educational intervention, 77% of women were willing to be tested for HR-HPV. Sixty-seven percent of women would be likely to return for their annual gynecologic examination even if a Pap smear was not required for 3 years. Education statistically reduced concern regarding a positive HR-HPV result with 60% pre-education and 27% posteducation very concerned (p =.002). When surveyed about what their concerns would be if tested positive for HR-HPV, women associate future cervical cancer diagnosis (38% pre-education vs 48% posteducation, p =.903) but not partner infidelity (0%) with testing positive for HR-HPV. Knowledge concerning HPV, cervical cancer, and cervical cancer screening was statistically improved after the educational intervention in all but 2 questions. Women 30 years and older are willing to have adjunct HR-HPV testing, with education reducing their degree of concern about testing positive. Women who test positive would be most concerned about getting cervical cancer. Women would be willing to return for yearly gynecologic examinations, even if a Pap smear was not needed for 3 years. Education improves women's knowledge of HPV, cervical cancer, and cervical cancer screening, but did not allay the concern for getting cervical cancer.

  1. Clinical characteristics of women diagnosed with carcinoma who tested positive for cervical and anal high-risk human papillomavirus DNA and E6 RNA.

    PubMed

    Veo, Carlos A R; Saad, Sarhan S; Fregnani, José Humberto T G; Scapulatempo-Neto, Cristovam; Tsunoda, Audrey Tieko; Resende, Júlio César Possati; Lorenzi, Adriana Tarlá; Mafra, Allini; Cinti, Claudia; Cotrim, Ismael Dale; Rosa, Luciana Albina Reis; de Oliveira, Cristina Mendes; Martins, Toni Ricardo; Centrone, Cristiane; Levi, José Eduardo; Longatto-Filho, Adhemar

    2015-07-01

    High-risk human papillomavirus (hrHPV) is an essential cause of cervical carcinoma and is also strongly related to anal cancer development. The hrHPV E6 oncoprotein plays a major role in carcinogenesis. We aimed to evaluate the frequency of hrHPV DNA and E6 oncoprotein in the anuses of women with cervical carcinoma. We analyzed 117 women with cervical cancer and 103 controls for hrHPV and the E6 oncogene. Positive test results for a cervical carcinoma included 66.7 % with hrHPV-16 and 7.7 % with hrHPV-18. One case tested positive for both HPV variants (0.9 %). The samples from the anal canal were positive for HPV-16 in 59.8 % of the cases. Simultaneous presence of HPV in the cervix and anal canal was found in 53.8 % of the cases. Regarding expression of E6 RNA, positivity for HPV-16 in the anal canal was found in 21.2 % of the cases, positivity for HPV-16 in the cervix was found in 75.0 %, and positivity for HPV-18 in the cervix was found in 1.9 %. E6 expression in both the cervix and anal canal was found in 19.2 % of the cases. In the controls, 1 % tested positive for HPV-16 and 0 % for HPV-18. Anal samples from the controls showed a hrHPV frequency of 4.9 % (only HPV16). The presence of hrHPV in the anal canal of women with cervical cancer was detected at a high frequency. We also detected E6 RNA expression in the anal canal of women with cervical cancer, suggesting that these women are at risk for anal hrHPV infection.

  2. Clinical evaluation of a GP5+/6+-based luminex assay having full high-risk human papillomavirus genotyping capability and an internal control.

    PubMed

    Geraets, D T; Cuschieri, K; de Koning, M N C; van Doorn, L J; Snijders, P J F; Meijer, C J L M; Quint, W G V; Arbyn, M

    2014-11-01

    The LMNX genotyping kit HPV GP (LMNX) is based on the clinically validated GP5+/6+ PCR, with a genotyping readout as an alternative for the more established enzyme immunoassay (EIA) detection of 14 targeted high-risk human papillomavirus (HPV) types. LMNX is additionally provided with an internal control probe. Here, we present an analysis of the clinical performance of the LMNX using a sample panel and infrastructure provided by the international VALGENT (Validation of Genotyping Tests) project. This panel consisted of cervical specimens from approximately 1,000 women attending routine screening, "enriched" with 300 women with abnormal cytology. Cases were defined as women classified with cervical intraepithelial neoplasia (CIN) grade 2+ (CIN2+) (n = 102) or CIN3+ (n = 55) within the previous 18 months. Controls were women who had normal cytology results over two subsequent screening rounds at a 3-year interval (n = 746). The GP5+/6+-PCR EIA (EIA) was used as a comparator assay and showed sensitivities of 94.1% and 98.2% for CIN2+ and CIN3+, respectively, with a clinical specificity of 92.4% among women aged ≥ 30 years. The LMNX demonstrated clinical sensitivities of 96.1% for CIN2+ and of 98.2% for CIN3+ and a clinical specificity of 92.6% for women aged ≥ 30 years. The LMNX and EIA were in high agreement (Cohen's kappa = 0.969) for the detection of 14 hrHPVs in aggregate, and no significant difference was observed (McNemar's P = 0.629). The LMNX internal control detected 0.6% inadequate specimens. Based on our study results, we consider the LMNX, similarly to the EIA, useful for HPV-based cervical cancer screening.

  3. Awareness and knowledge of human papillomavirus (HPV) infection among high-risk men of Hispanic origin attending a sexually transmitted infection (STI) clinic.

    PubMed

    Colón-López, Vivian; Ortiz, Ana P; Del Toro-Mejías, Lizbeth M; García, Hermes; Clatts, Michael C; Palefsky, Joel

    2012-12-12

    Genital human papillomavirus (HPV) is one of the most commonly diagnosed sexually transmitted infection (STIs) in men and women. Knowledge about HPV infection among men is limited. This study aims to determine correlates of adequate knowledge of HPV infection among men who attend an STI clinic in Puerto Rico. A cross-sectional study of 206 men was conducted at an STI clinic in San Juan, PR. Adequate knowledge was defined as a score of at least 70% of correct responses among those men who reported having ever heard of HPV. Variables that achieved statistical significance in the bivariate analysis (p<0.05) were included in the multivariate logistic regression model. Although 52.5% of men reported having heard of HPV infection before the survey, only 29.3% of this sub-group had an adequate knowledge of HPV. Most men did not know that HPV is a risk factor for anal (38.7%), penile (50.0%) and oral (72.6%) cancer. Factors associated with adequate knowledge of HPV in age-adjusted models were being men who have sex with men (MSM) (OR=2.6;95%CI=1.1-6.1), self-report of genital warts (OR=3.2;95%CI=1.3-7.9) and herpes (OR=7.4;95% CI=2.2-25.1). MSM was marginally associated with adequate knowledge (OR=2.3;95% CI=0.9-5.9) and self-report of herpes remained significantly associated (OR=5.0;95%CI=1.3-18.4) in multivariate logistic regression analysis. Awareness and knowledge of HPV was very low in this group of men. Interventions to increase knowledge and awareness in this group are necessary to promote preventive practices for HPV-related cancers in high-risk groups.

  4. High-Risk Human Papillomavirus (HPV) Infection and Cervical Cancer Prevention in Britain: Evidence of Differential Uptake of Interventions from a Probability Survey.

    PubMed

    Tanton, Clare; Soldan, Kate; Beddows, Simon; Mercer, Catherine H; Waller, Jo; Field, Nigel; Clifton, Soazig; Copas, Andrew J; Panwar, Kavita; Manyenga, Precious; da Silva, Filomeno; Wellings, Kaye; Ison, Catherine A; Johnson, Anne M; Sonnenberg, Pam

    2015-05-01

    The third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3) provides an opportunity to explore high-risk human papillomavirus (HR-HPV) and uptake of cervical screening and HPV vaccination in the general population. Natsal-3, a probability sample survey of men and women ages 16 to 74, resident in Britain, interviewed 8,869 women in 2010 to 2012. We explored risk factors for HR-HPV (in urine from 2,569 sexually experienced women ages 16 to 44), nonattendance for cervical screening in the past 5 years, and noncompletion of HPV catch-up vaccination. HR-HPV was associated with increasing numbers of lifetime partners, younger age, increasing area-level deprivation, and smoking. Screening nonattendance was associated with younger and older age, increasing area-level deprivation (age-adjusted OR 1.91, 95% confidence interval, 1.48-2.47 for living in most vs. least deprived two quintiles), Asian/Asian British ethnicity (1.96, 1.32-2.90), smoking (1.97, 1.57-2.47), and reporting no partner in the past 5 years (2.45, 1.67-3.61 vs. 1 partner) but not with HR-HPV (1.35, 0.79-2.31). Lower uptake of HPV catch-up vaccination was associated with increasing area-level deprivation, non-white ethnicity, smoking, and increasing lifetime partners. Socioeconomic markers and smoking were associated with HR-HPV positivity, nonattendance for cervical screening, and noncompletion of catch-up HPV vaccination. The cervical screening program needs to engage those missing HPV catch-up vaccination to avoid a potential widening of cervical cancer disparities in these cohorts. As some screening nonattenders are at low risk for HR-HPV, tailored approaches may be appropriate to increase screening among higher-risk women. ©2015 American Association for Cancer Research.

  5. High sensitivity, loop-mediated isothermal amplification combined with colorimetric gold-nanoparticle probes for visual detection of high risk human papillomavirus genotypes 16 and 18.

    PubMed

    Kumvongpin, Ratchanida; Jearanaikool, Patcharee; Wilailuckana, Chotechana; Sae-Ung, Nattaya; Prasongdee, Prinya; Daduang, Sakda; Wongsena, Metee; Boonsiri, Patcharee; Kiatpathomchai, Wansika; Swangvaree, Sukumarn Sanersak; Sandee, Alisa; Daduang, Jureerut

    2016-08-01

    High-risk human papillomavirus (HR-HPV) causes cervical cancer. HPV16 and HPV18 are the most prevalent strains of the virus reported in women worldwide. Loop-mediated isothermal amplification (LAMP) is an alternative method for DNA detection under isothermal conditions. However, it results in a turbid amplified product which is not easily detected by the naked eye. This study aimed to develop an improved technique by using gold nanoparticles (AuNPs) attached to a single-stranded DNA probe for the detection of HPV16 and HPV18. Detection of the LAMP product by AuNP color change was compared with detection by visual turbidity. The optimal conditions for this new LAMP-AuNP assay were an incubation time of 20min and a temperature of 65°C. After LAMP amplification was complete, its products were hybridized with the AuNP probe for 5min and then detected by the addition of magnesium salt. The color changed from red to blue as a result of aggregation of the AuNP probe under high ionic strength conditions produced by the addition of the salt. The sensitivity of the LAMP-AuNP assay was greater than the LAMP turbidity assay by up to 10-fold for both HPV genotypes. The LAMP-AuNP assay showed higher sensitivity and ease of visualization than did the LAMP turbidity for the detection of HPV16 and HPV18. Additionally, AuNP-HPV16 and AuNP-HPV18 probes were stable for over 1year. The combination of LAMP and the AuNP-probe colorimetric assay offers a simple, rapid and highly sensitive alternative diagnostic tool for the detection of HPV16 and HPV18 in district hospitals or field studies.

  6. Pre-vaccination prevalence of infections with 25 non-high-risk human papillomavirus types among 1,000 Slovenian women in cervical cancer screening.

    PubMed

    Učakar, Veronika; Poljak, Mario; Oštrbenk, Anja; Klavs, Irena

    2014-10-01

    Cervical infections with non-high-risk human papillomavirus (non-HR-HPV) types have been associated with genital warts and a fraction of atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions. The pre-vaccination prevalence of cervical infections with 25 non-HR-HPV types has been estimated, regardless of and without the coexistence of infection with HR-HPV types among Slovenian women 20-64 years old in cervical cancer screening, overall and according to age and cytology result. One thousand cervical specimens selected randomly from 4,455 specimens collected in 2010 in the Slovenian HPV prevalence survey were tested with Linear Array HPV Genotyping Test. Prevalence of cervical infections with any of the 25 non-HR-HPV types was 10.0% (95% CI: 8.1-11.9%) and with exclusively non-HR-HPV types 4.5% (95% CI: 3.2-5.8%). Prevalence of infections with any non-HR-HPV types among women with normal cytology was 8.8%, with atypical squamous cells of undetermined significance 30.4%, with low-grade squamous intraepithelial lesions 60.0%, and with high-grade squamous intraepithelial lesions 7.7%. Non-HR-HPV types without coexisting HR-HPV types were found in 4.0% of women with normal cytology, 26.1% with atypical squamous cells of undetermined significance, 6.7% with low-grade squamous intraepithelial lesions, and none with high-grade squamous intraepithelial lesion. Non-HR-HPV type cervical infections without coexisting HR-HPV infections were common among Slovenian women in cervical cancer screening with atypical squamous cells of undetermined significance, while rare in those with low-grade squamous intraepithelial lesions or worse. J. Med. Virol. 86: 1772-1779, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

  7. p16/Ki-67 co-expression associates high risk human papillomavirus persistence and cervical histopathology: a 3-year cohort study in China.

    PubMed

    Yu, Lu-Lu; Guo, Hui-Qin; Lei, Xiao-Qin; Qin, Yu; Wu, Ze-Ni; Kang, Le-Ni; Zhang, Xun; Qiao, You-Lin; Chen, Wen

    2016-10-04

    To evaluate the association of p16/Ki-67 co-expression and persistence of high-risk human papillomavirus (HR-HPV) infection as well as cervical abnormalities. We performed a 3-year cohort study among which 2498 Chinese women aged 25 to 65 years were screened by different HPV tests in 2011. 690 women who were positive at any of the tests and a random sample of 164 women with all negative results received colposcopy, cervical specimens for cobas HPV test (Roche diagnostics) were collected before colposcopy; of this group, 737 cervical specimens were collected to perform cobas, Liquid-based cytology, HPV E6 test (Arbor Vita Corporation) and p16/Ki-67 dual staining (Roche diagnostics) in 2014. Colposcopy and biopsies was performed on women with any abnormal result. Compared to women without HR-HPV persistent infection, women in the HR-HPV persistence group had a higher risk of p16/Ki-67 positive, with an adjusted Odds Ratio(OR) and 95% confidence interval (CI) of 6.29 (4.07-9.72); moreover, adjusted odds ratio for women who had HPV16/18 persistent infection was nearly 4-folder higher than women with other 12 HR-HPV persistent infection (adjusted OR = 17.15, 95% CI: 7.11-41.33 vs adjusted OR = 4.68, 95% CI: 2.89-7.58). Additionally, p16/Ki-67 positivity rate significantly increased with the severity of the cytological and histological abnormalities, and resulted strongly associated with a CIN2+ diagnosis (OR = 16.03, 95% CI: 4.46-57.59). p16/Ki-67 co-expressions associated strongly with HR-HPV persistence, especially with HPV16/18, and the presence of a CIN2+ lesion. Therefore, p16/Ki-67 could be considered as a suitable biomarker for cervical cancer screening, particularly in HPV-based screening programs.

  8. P16 and Ki-67 expression improves the diagnostic accuracy of cervical lesions but not predict persistent high risk human papillomavirus infection with CIN1

    PubMed Central

    Zhong, Pingping; Li, Jifeng; Gu, Yiqun; Liu, Yu; Wang, Aichun; Sun, Yunfei; Lu, Lijuan

    2015-01-01

    Objective: To determine the association between the expression of p16 and Ki-67 and cervical lesions, and to evaluate the role of p16 and Ki-67 as prognostic markers for persistent high risk human papillomavirus (hr-HPV) infection. Methods: Totally 1,154 cases of cervical biopsies were enrolled, 331 cases with negative for dysplasia (NEG), 462 with cervical intraepithelial neoplasia 1 (CIN1), 176 with CIN2, 163 with CIN3 and 22 with cervical squamous cell carcinoma (SCC). Furthermore, 283 women with CIN1 were recruited into 12-month follow-up, and HPV specific gene detection by polymerase chain reaction was used to detect hr-HPV of cervical secretions at 6-month-interval for 12-month follow-up period. 40 women were infected with persistent hr-HPV, 182 with transient infection and 61 unfected with hr-HPV. The expression of p16 and Ki-67 were evaluated by immunohistochemical method. The immunostaining results of p16 and Ki-67 were classified into four categories: negative, 1+, 2+ and 3+. Results: There was significant increase in the expression of p16 (P < 0.001) and Ki-67 (P < 0.001) from NEG to SCC. The expression of Ki-67 (P < 0.001) but not p16 (P = 0.254) significantly increased in CIN2, CIN3. Ratio of p16 (P = 0.215) and Ki-67 (P = 0.495) positivity were not correlated with persistent hr-HPV infection. Conclusion: P16 and Ki-67 can improve the diagnostic accuracy of cervical lesions but can not predict persistent hr-HPV infection with CIN1. PMID:26045807

  9. P16 and Ki-67 expression improves the diagnostic accuracy of cervical lesions but not predict persistent high risk human papillomavirus infection with CIN1.

    PubMed

    Zhong, Pingping; Li, Jifeng; Gu, Yiqun; Liu, Yu; Wang, Aichun; Sun, Yunfei; Lu, Lijuan

    2015-01-01

    To determine the association between the expression of p16 and Ki-67 and cervical lesions, and to evaluate the role of p16 and Ki-67 as prognostic markers for persistent high risk human papillomavirus (hr-HPV) infection. Totally 1,154 cases of cervical biopsies were enrolled, 331 cases with negative for dysplasia (NEG), 462 with cervical intraepithelial neoplasia 1 (CIN1), 176 with CIN2, 163 with CIN3 and 22 with cervical squamous cell carcinoma (SCC). Furthermore, 283 women with CIN1 were recruited into 12-month follow-up, and HPV specific gene detection by polymerase chain reaction was used to detect hr-HPV of cervical secretions at 6-month-interval for 12-month follow-up period. 40 women were infected with persistent hr-HPV, 182 with transient infection and 61 unfected with hr-HPV. The expression of p16 and Ki-67 were evaluated by immunohistochemical method. The immunostaining results of p16 and Ki-67 were classified into four categories: negative, 1+, 2+ and 3+. There was significant increase in the expression of p16 (P<0.001) and Ki-67 (P<0.001) from NEG to SCC. The expression of Ki-67 (P<0.001) but not p16 (P=0.254) significantly increased in CIN2, CIN3. Ratio of p16 (P=0.215) and Ki-67 (P=0.495) positivity were not correlated with persistent hr-HPV infection. P16 and Ki-67 can improve the diagnostic accuracy of cervical lesions but can not predict persistent hr-HPV infection with CIN1.

  10. Performance of a Branch Chain RNA In Situ Hybridization Assay for the Detection of High-risk Human Papillomavirus in Head and Neck Squamous Cell Carcinoma.

    PubMed

    Kerr, Darcy A; Arora, Kshitij S; Mahadevan, Krishnan K; Hornick, Jason L; Krane, Jeffrey F; Rivera, Miguel N; Ting, David T; Deshpande, Vikram; Faquin, William C

    2015-12-01

    High-risk human papillomavirus (HR-HPV) is a major etiologic agent in a subset of head and neck squamous cell carcinomas (HNSCCs), and its recognition has prognostic and predictive implications. The availability of a sensitive and specific test to assess HR-HPV status is limited. We evaluate an RNA in situ hybridization (ISH) method using branch chain technology to detect HR-HPV and compare its results with DNA ISH, p16 immunohistochemistry, and polymerase chain reaction (PCR). Tissue sections from 54 patients were stained with a manual RNA ISH assay (ViewRNA), which detects 14 HR-HPV types, an automated DNA ISH assay, and p16 immunohistochemistry. Most cases (83%, n=45) were also tested on an automated platform for 14 HR-HPV types and 1 limited to HPV 16/18. PCR was performed in all cases and was successful in 93% (n=50). The RNA ISH assay produced results in 96% of the cases with strong signals and was easily interpreted. HR-HPV was detected in more cases (63%, n=34) by RNA ISH than by DNA ISH (39%, n=21). Compared with PCR, both ISH platforms were 94% specific. RNA ISH was more sensitive (91%) than DNA ISH (65%), and RNA ISH correlated more strongly with p16 immunostaining. HPV 16 represented 89% of HR-HPV detected. The cocktail HPV 16/18 platform was concordant with the pooled HR-HPV assay in all expected cases. The automated assay demonstrated high concordance (96%) with the manual version, showed decreased background, and should allow for easy implementation into the workflow of the diagnostic pathology laboratory.

  11. Clinical Evaluation of a GP5+/6+-Based Luminex Assay Having Full High-Risk Human Papillomavirus Genotyping Capability and an Internal Control

    PubMed Central

    Cuschieri, K.; de Koning, M. N. C.; van Doorn, L. J.; Snijders, P. J. F.; Meijer, C. J. L. M.; Quint, W. G. V.; Arbyn, M.

    2014-01-01

    The LMNX genotyping kit HPV GP (LMNX) is based on the clinically validated GP5+/6+ PCR, with a genotyping readout as an alternative for the more established enzyme immunoassay (EIA) detection of 14 targeted high-risk human papillomavirus (HPV) types. LMNX is additionally provided with an internal control probe. Here, we present an analysis of the clinical performance of the LMNX using a sample panel and infrastructure provided by the international VALGENT (Validation of Genotyping Tests) project. This panel consisted of cervical specimens from approximately 1,000 women attending routine screening, “enriched” with 300 women with abnormal cytology. Cases were defined as women classified with cervical intraepithelial neoplasia (CIN) grade 2+ (CIN2+) (n = 102) or CIN3+ (n = 55) within the previous 18 months. Controls were women who had normal cytology results over two subsequent screening rounds at a 3-year interval (n = 746). The GP5+/6+-PCR EIA (EIA) was used as a comparator assay and showed sensitivities of 94.1% and 98.2% for CIN2+ and CIN3+, respectively, with a clinical specificity of 92.4% among women aged ≥30 years. The LMNX demonstrated clinical sensitivities of 96.1% for CIN2+ and of 98.2% for CIN3+ and a clinical specificity of 92.6% for women aged ≥30 years. The LMNX and EIA were in high agreement (Cohen's kappa = 0.969) for the detection of 14 hrHPVs in aggregate, and no significant difference was observed (McNemar's P = 0.629). The LMNX internal control detected 0.6% inadequate specimens. Based on our study results, we consider the LMNX, similarly to the EIA, useful for HPV-based cervical cancer screening. PMID:25210073

  12. Prevalence of anal high-risk human papillomavirus infections among HIV-positive and HIV-negative men who have sex with men (MSM) in Nigeria

    PubMed Central

    Nowak, Rebecca G.; Gravitt, Patti E.; He, Xin; Ketende, Sosthenes; Anom, Wuese; Omuh, Helen; Blattner, William A.; Charurat, Manhattan E.

    2016-01-01

    Background Prevalence estimates of anal high-risk human papillomavirus (HR-HPV) are needed in sub-Saharan Africa where HIV is endemic. This study evaluated anal HR-HPV in Nigeria among HIV-positive and HIV-negative men who have sex with men (MSM) for future immunization recommendations. Methods We conducted a cross-sectional study to compare the prevalence of anal HR-HPV infections between 64 HIV-negative and 90 HIV-positive MSM. Multivariate Poisson regression analyses were used to examine demographic and behavioral risk factors associated with any HR-HPV infections. Results The median age of the 154 participants was 25 years (interquartile range [IQR]: 22-28, range: 16-38) and the median age at initiation of anal sex with another man was 16 years (IQR: 13-18, range: 7-29). The prevalence of anal HR-HPV was higher among HIV-positive than HIV-negative MSM (91.1% vs. 40.6%, p<0.001). In the multivariate analysis, HIV infection (adjusted prevalence ratio [aPR]: 2.02, 95% CI: 1.49-2.72), ten years or more since anal sexual debut (aPR: 1.26, 95% CI: 1.07-1.49), and concurrent relationships with men (aPR: 1.32, 95% CI: 1.04-1.67) were associated with increased anal HR-HPV prevalence. Conclusions Anal HR-HPV infection is high for young Nigerian MSM and rates are amplified in those co-infected with HIV. Providing universal coverage as well as catchup immunization for young MSM may be an effective anal cancer prevention strategy in Nigeria. PMID:26967301

  13. Performance of the Roche cobas 4800 high-risk human papillomavirus test in cytologic preparations of squamous cell carcinoma of the head and neck.

    PubMed

    Kerr, Darcy A; Pitman, Martha B; Sweeney, Brenda; Arpin, Ronald N; Wilbur, David C; Faquin, William C

    2014-03-01

    Determining high-risk human papillomavirus (HR-HPV) status of head and neck squamous cell carcinoma (HNSCC) defines a tumor subset with important clinical implications. Cytologic sampling often provides the sentinel or sole diagnostic specimen. The authors assessed the performance characteristics for the Roche cobas 4800 HPV real-time polymerase chain reaction (PCR)-based system (cobas) on cytologic specimens of HNSCC compared with standard methods of in situ hybridization (ISH) for HR-HPV and immunohistochemistry (IHC) for p16 on formalin-fixed, paraffin-embedded (FFPE) tissue. Samples of HNSCC were collected by fine-needle aspiration and from surgical biopsies or resections, fixed, and processed with the cobas system. Available corresponding FFPE samples were synchronously evaluated for HR-HPV using ISH and IHC. Discrepant cases underwent additional PCR studies for adjudication. Thirty-six samples from 33 patients were analyzed. Forty-two percent (n = 15) of tumors were positive for HR-HPV according to cobas. Corresponding histology with ISH (n = 30) was concordant in 91% of samples. Compared with the adjudication PCR standard, there were 3 false-positive cases according to cobas. Ninety-two percent (n = 12) of cases were the HPV16 subtype. The overall sensitivity for the cobas system was 100%, and the specificity was 86%. Concordance in HNSCC HR-HPV status between cobas and ISH/IHC was > 90%, and cobas demonstrated a sensitivity of 100% and a specificity of 86%, broadening options for HR-HPV testing of fine-needle aspiration samples. Advantages for this system include subtyping of HR-HPV and the ability to discern HR-HPV status earlier in a patient's treatment course. © 2013 American Cancer Society.

  14. p16/Ki-67 co-expression associates high risk human papillomavirus persistence and cervical histopathology: a 3-year cohort study in China

    PubMed Central

    Yu, Lu-Lu; Guo, Hui-Qin; Lei, Xiao-Qin; Qin, Yu; Wu, Ze-Ni; Kang, Le-Ni; Zhang, Xun; Qiao, You-Lin; Chen, Wen

    2016-01-01

    Purpose To evaluate the association of p16/Ki-67 co-expression and persistence of high-risk human papillomavirus (HR-HPV) infection as well as cervical abnormalities. Methods We performed a 3-year cohort study among which 2498 Chinese women aged 25 to 65 years were screened by different HPV tests in 2011. 690 women who were positive at any of the tests and a random sample of 164 women with all negative results received colposcopy, cervical specimens for cobas HPV test (Roche diagnostics) were collected before colposcopy; of this group, 737 cervical specimens were collected to perform cobas, Liquid-based cytology, HPV E6 test (Arbor Vita Corporation) and p16/Ki-67 dual staining (Roche diagnostics) in 2014. Colposcopy and biopsies was performed on women with any abnormal result. Results Compared to women without HR-HPV persistent infection, women in the HR-HPV persistence group had a higher risk of p16/Ki-67 positive, with an adjusted Odds Ratio(OR) and 95% confidence interval (CI) of 6.29 (4.07-9.72); moreover, adjusted odds ratio for women who had HPV16/18 persistent infection was nearly 4-folder higher than women with other 12 HR-HPV persistent infection (adjusted OR = 17.15, 95% CI: 7.11-41.33 vs adjusted OR = 4.68, 95% CI: 2.89-7.58). Additionally, p16/Ki-67 positivity rate significantly increased with the severity of the cytological and histological abnormalities, and resulted strongly associated with a CIN2+ diagnosis (OR = 16.03, 95% CI: 4.46-57.59). Conclusions p16/Ki-67 co-expressions associated strongly with HR-HPV persistence, especially with HPV16/18, and the presence of a CIN2+ lesion. Therefore, p16/Ki-67 could be considered as a suitable biomarker for cervical cancer screening, particularly in HPV-based screening programs. PMID:27588487

  15. Evaluation of the detection of 14 high-risk human papillomaviruses with HPV 16 and HPV 18 genotyping for cervical cancer screening

    PubMed Central

    BIAN, MEI-LU; CHENG, JIAO-YING; MA, LI; CONG, XIAO; LIU, JUN; CHEN, YING; CHEN, XI

    2013-01-01

    The American Society for Colposcopy and Cervical Pathology (ASCCP) suggests that women ≥30 years old, with a negative cytopathological test but a positive high-risk (HR) human papillomavirus (HPV) test should undergo HPV 16 and HPV 18 genotyping. If this test is positive, immediate cervical pathology is required. Therefore, the aim of this study was to evaluate the effectiveness and clinical value of testing for 14 HR HPVs with HPV 16 and HPV 18 genotyping for cervical cancer (CC) screening. A total of 424 females from the China-Japan Friendship Hospital were selected and randomly divided into two groups (A and B). All participants underwent two different testing methods: the liquid-based cytology test (LCT) and a HPV DNA test. For the HPV DNA test, participants in group A underwent the hybrid capture II (HC-II) testing method while participants in group B were tested using the quantitative polymerase chain reaction (qPCR; HBRT-H14) method. The sensitivity, specificity, positive predictive value and negative predictive value for the detection of cervical intraepithelial neoplasia (CIN) grade II or greater using HBRT-H14 were 96.30, 78.17, 23.21 and 99.68%, respectively. In Group B, compared with other HR HPV types, HPV 16 and HPV 18 infection led to the increased possibility of cervical lesions graded CIN II or higher (8.11 and 51.28%, respectively). A significant difference in the rates of CC and CIN II or higher was observed among women who were i) infected with HPV 16 and/or HPV 18, ii) infected with other HR HPV types and iii) diagnosed as negative for HR HPV infection (χ2=93.976, P=0.0001). In conclusion, HBRT-H14 is applicable for CC screening with the advantage of genotyping for HPV 16 and HPV 18, which may help to improve triage management for women with negative cytology. PMID:24223668

  16. Genotyping of high-risk human papillomaviruses in p16/Ki-67-positive urothelial carcinoma cells: even a worm will turn.

    PubMed

    Advenier, A-S; Casalegno, J-S; Mekki, Y; Decaussin-Petrucci, M; Mège-Lechevallier, F; Ruffion, A; Piaton, E

    2015-04-01

    Co-expression of p16INK4a protein and Ki-67 (p16/Ki-67) is noted in almost all high-grade urothelial lesions. However, the aetiological role or, conversely, the absence of causative effect of high-risk human papillomaviruses (hr-HPVs) has not been documented. The purpose of this study is to evaluate HPV DNA in p16/Ki-67-positive, high-grade urothelial tumour cells. Fifty-seven urine samples collected from 50 patients, including 55 histologically proven high-grade proliferations and two cases with clinical evidence of malignancy, were analysed for p16/Ki-67. Immunolabelling was performed in destained Papanicolaou-stained slides after ThinPrep(®) processing. HPV genotyping was performed by polymerase chain reaction (PCR) using a DNA microarray for 35 HPV types. Confirmation of the presence (or absence) of HPV in tissue samples was verified using a reasoned approach combining PCR and in situ hybridization (ISH) for hr-HPVs. Co-expression of p16/Ki-67 was noted in 43 of 57 (75.4%) cases. In these, hr-HPVs 16, 31 and 70, and low risk HPV 84, were detected in the urine in four patients (8%). Upregulation of p16INK4a protein was confirmed on bladder biopsy or transurethral resection specimens, but PCR and ISH for hr-HPVs were both negative on the tissue sections. Our results show a low prevalence of HPV infection in the urinary tract of patients with p16/Ki-67-positive urothelial malignancy. The study confirms that the deregulated cell cycle, as demonstrated by p16/Ki-67 dual labelling, is independent of the oncogenic action of hr-HPVs in high-grade urothelial proliferations. © 2014 John Wiley & Sons Ltd.

  17. Vaginal high-risk human papillomavirus infection in a cross-sectional study among women of six different ethnicities in Amsterdam, the Netherlands: the HELIUS study.

    PubMed

    Alberts, C J; Vos, R A; Borgdorff, H; Vermeulen, W; van Bergen, J; Bruisten, S M; Geerlings, S E; Snijder, M B; van Houdt, R; Morré, S A; de Vries, H J C; van de Wijgert, J H H M; Prins, M; Schim van der Loeff, M F

    2016-12-01

    In the Netherlands the incidence of cervical cancer is higher among ethnic minority populations compared with the general Dutch population. We investigated the prevalence of, and risk factors associated with, vaginal high-risk human papillomavirus (hrHPV) infection in women of six different ethnicities living in Amsterdam. For this cross-sectional study we selected women aged 18-34 years old of six ethnicities from the large-scale multiethnic HEalthy LIfe in an Urban Setting study. Self-collected vaginal swabs were tested for HPV DNA and genotyped using a highly sensitive PCR and reverse line blot assay (short PCR fragment (SPF)10-PCR DNA enzyme immunoassay/LiPA25-system version-1, delft diagnostic laboratory (DDL)). Participants completed a questionnaire regarding demographics and sexual behaviour. Logistic regression using generalised estimating equations was used to assess risk factors of hrHPV, and to investigate whether prevalence of hrHPV differed among ethnicities. The study population consisted of 592 women with a median age of 27 (IQR: 23-31) years. Dutch and African Surinamese women reported the highest sexual risk behaviour. HrHPV prevalence was highest in the Dutch (40%) followed by the African Surinamese (32%), Turkish (29%), Ghanaian (26%), Moroccan (26%) and South-Asian Surinamese (18%). When correcting for sexual risk behaviour, the odds to be hrHPV-positive were similar for all non-Dutch groups when compared with that of the Dutch group. We found an overall higher hrHPV prevalence and higher sexual risk behaviour in the native Dutch population. Further research is needed to unravel the complex problem concerning cervical cancer disparities, such as differences in participation in the cervical cancer screening programme, or differences in clearance and persistence of hrHPV. 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/.

  18. High-risk human papillomavirus seroprevalence in men and women of six different ethnicities in Amsterdam, the Netherlands: The HELIUS study.

    PubMed

    Alberts, C J; Michel, A; Bruisten, S; Snijder, M B; Prins, M; Waterboer, T; Schim van der Loeff, M F

    2017-06-01

    Ethnic variations in the (sero)prevalence of Human Papillomavirus (HPV) and HPV related diseases have been observed previously. We explored if high-risk HPV (hrHPV) seropositivity indeed differs among 6 ethnic groups in Amsterdam the Netherlands and assessed if hrHPV seroprevalence is higher among women than men within each ethnic group, both after adjustment for confounders. From the multi-ethnic HEalthy Life In an Urban Setting (HELIUS) study in Amsterdam (the Netherlands) we randomly selected 4637 men and women aged 18-44 years with a Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Moroccan, or Turkish ethnicity. Blood samples were tested for HPV-16,-18,-31,-33,-45,-52, and -58 antibodies using a validated Luminex-based multiplex serology assay. We assessed the association of both ethnicity and gender with hrHPV seropositivity using logistic regression models with generalised estimating equations. The hrHPV seroprevalence in Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Moroccan, and Turkish participants was 18%, 12%, 23%, 19%, 17%, and 15% in men, and 30%, 22%, 34%, 31%, 14%, and 15% in women, respectively. HrHPV seroprevalence of non-Dutch men did not differ significantly from Dutch men. HrHPV seroprevalence was significantly higher among African Surinamese women, and significantly lower among Moroccan and Turkish women when compared to Dutch women. These differences were not significant anymore after adjustment for demographic, health, and sexual behavioural differences between ethnicities. HrHPV seroprevalence varied by age, age of sexual debut, and lifetime sexual partners among women but not among men. Seroprevalence of hrHPV was higher among women than among men, except in the Turkish group. Among women hrHPV seroprevalence differed by ethnicity, yet among men no pronounced differences were observed across ethnicities. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Population-based prevalence of cervical infection with human papillomavirus genotypes 16 and 18 and other high risk types in Tlaxcala, Mexico.

    PubMed

    Rudolph, Samantha E; Lorincz, Attila; Wheeler, Cosette M; Gravitt, Patti; Lazcano-Ponce, Eduardo; Torres-Ibarra, Leticia; León-Maldonado, Leith; Ramírez, Paula; Rivera, Berenice; Hernández, Rubí; Franco, Eduardo L; Cuzick, Jack; Méndez-Hernández, Pablo; Salmerón, Jorge

    2016-09-01

    Cervical cancer remains an important cause of cancer mortality for Mexican women. HPV 16/18 typing may help to improve cervical cancer screening. Here we present the prevalence of high-risk human papillomavirus (hrHPV) including HPV16 and HPV18 from the FRIDA (Forwarding Research for Improved Detection and Access) population. Beginning in 2013, we recruited 30,829 women aged 30-64 in Tlaxcala, Mexico. Cervical samples were collected and tested for 14 hrHPV genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68). We used logistic regression to estimate odds ratios with 95 % confidence intervals for hrHPV infections according to putative risk factors. Prevalence of infection with any of the 14 hrHPV types was 11.0 %. The age-specific prevalence of all hrHPV formed a U-shaped curve with a higher prevalence for women aged 30-39 and 50-64 than women aged 40-49. Across all age groups, 2.0 % of women were positive for HPV16 and/or HPV18 (HPV16/18), respectively. HPV16/18 prevalence also showed a U-shaped curve with increased prevalence estimates for women aged both 30-39 and 60-64. Both prevalence curves had a significant quadratic age coefficient. Infections with hrHPV were positively associated with an increased number of lifetime sexual partners, a history of sexually transmitted disease, being unmarried, use of hormonal contraception, having a history of smoking and reported condom use in the multivariate model. The FRIDA population has a bimodal distribution of both hrHPV and HPV16/18 positivity with higher prevalences at ages 30-39 and 60-64. These findings will help to evaluate triage algorithms based on HPV genotyping. The trial is registered with ClinicalTrials.gov, number NCT02510027 .

  20. High-risk human papillomavirus types in HIV-infected and HIV-uninfected young women in KwaZulu-Natal, South Africa: implications for vaccination.

    PubMed

    Mbatha, Joyce N; Taylor, Myra; Kleppa, Elisabeth; Lillebo, Kristine; Galapaththi-Arachchige, Hashini N; Singh, Deepak; Kjetland, Eyrun F; Baay, Marc F D; Mkhize-Kwitshana, Zilungile L

    2017-08-01

    High-risk human papillomavirus (hr-HPV) infections and low-grade squamous intraepithelial lesions occur frequently in young women. The available vaccines cover up to seven hr-HPV genotypes (HPV16, HPV18, HPV31, HPV33, HPV45, HPV52 and HPV58) and two low-risk HPV types (HPV6 and HPV11). The objective of this study was to describe the hr-HPV genotypes present among HIV-uninfected and HIV-infected young women in rural high schools. Cervicovaginal lavages were obtained from sexually active young women recruited from high schools in KwaZulu-Natal (n = 1223). HPV testing was done by the polymerase chain reaction using GP5+/GP6 + primers and enzyme immunoassay. HIV testing was done using rapid test kits. Of the 1223 cervicovaginal lavages, 301 (25%) were positive for hr-HPV. The HPV prevalence was higher in HIV infected (32.20%, 95% CI: 0.27-0.38) than in HIV-uninfected women (22.50%, 95% CI: 0.21-0.26), (p = .001). Similarly, multiple infections were slightly more common in HIV infected (59.32%) than in HIV-uninfected women (53.51%), (p = .37). The nine predominant genotypes in descending order were HPV types 16 (n = 99, 22.10%), 51 (n = 58, 12.91%), 18 (n = 56, 12.50%), 35 (n = 50, 11.10%), 33 (n = 47, 10.82%), 56 (n = 42, 9.31%), 45 (n = 34, 7.60%), 52 (n = 32, 7.14%) and 59 (n = 31, 6.91%). HPV 35, 51, 56 and 59 (40.62%), which are not covered by any vaccine, were among the most prevalent in the schools of KwaZulu-Natal. Four of the most predominant high-risk HPV types in this region are not covered by the new nine-valent HPV vaccine.

  1. Prevalence of High-Risk Human Papillomavirus (HR-HPV) Genotypes and Multiple Infections in Cervical Abnormalities from Northern Xinjiang, China.

    PubMed

    Wang, Lina; Wang, Pengyan; Ren, Yan; Du, Jingyun; Jiang, Jianjun; Jia, Xuesong; Chen, Chuangfu; Wang, Yuanzhi

    2016-01-01

    Multiple human papillomavirus (HPV) genotypes often coexist within the cervical epithelia and are frequently detected together in various grades of the cervical neoplasia. To date, only a few reports exist on multiple HPV infections of HPV in Xinjiang Uygur Autonomous Region (XUAR). In the present study, we investigated the prevalence of High-Risk HPV (HR-HPV) genotypes and multiple infections. Cervical cytology samples were collected from 428 women who presented cervical abnormalities. Genotyping of HPV was performed by polymerase chain reaction-sequencing based typing (PCR-SBT) using consensus primers and specific primers. Of them, 166 samples were positive for HPV according to PCR results using the consensus primers. These samples contained cervical abnormalities enriched with inflammation (n = 107), cervical intraepithelial neoplasia (CIN) I (n = 19), CINII-III (n = 9) and cervical cancer (n = 31). Of the 166 HPV positive samples as determined by PCR analysis, 151 were further typed by PCR-SBT using 19 pairs of genotype-specific primers. Using this method, 17 different HR-HPV genotypes were identified. The most frequently observed HPV genotypes were HPV16 (44.0%, 73/166), 53 (28.9%, 48/166), 52 (25.3%, 42/166), 58 (22.3%, 37/166) and 35 (17.5%, 29/166). The proportions of single and multiple infections in the HPV-positive specimens were 34.9% and 65.1%, respectively. Multiple HPV types were most prevalent in the inflammatory state (63.0%), followed by cervical cancer (24.1%), CINI (11.1%), and CINII-III (1.9%). The results of our data analyses suggested that i) multiple HPV infection is not necessarily correlated with the severity of cervical abnormalities; and ii) among the multiple HPV infections, double infections combined with HPV16 is the most common. In addition, L1 full-length sequences of the top five high-risk HPV genotypes were amplified and sequenced. According to the L1 sequence of the epidemic genotypes that were amplified, we found that these

  2. Prevalence of High-Risk Human Papillomavirus (HR-HPV) Genotypes and Multiple Infections in Cervical Abnormalities from Northern Xinjiang, China

    PubMed Central

    Du, Jingyun; Jiang, Jianjun; Jia, Xuesong; Chen, Chuangfu; Wang, Yuanzhi

    2016-01-01

    Multiple human papillomavirus (HPV) genotypes often coexist within the cervical epithelia and are frequently detected together in various grades of the cervical neoplasia. To date, only a few reports exist on multiple HPV infections of HPV in Xinjiang Uygur Autonomous Region (XUAR). In the present study, we investigated the prevalence of High-Risk HPV (HR-HPV) genotypes and multiple infections. Cervical cytology samples were collected from 428 women who presented cervical abnormalities. Genotyping of HPV was performed by polymerase chain reaction–sequencing based typing (PCR-SBT) using consensus primers and specific primers. Of them, 166 samples were positive for HPV according to PCR results using the consensus primers. These samples contained cervical abnormalities enriched with inflammation (n = 107), cervical intraepithelial neoplasia (CIN) I (n = 19), CINII-III (n = 9) and cervical cancer (n = 31). Of the 166 HPV positive samples as determined by PCR analysis, 151 were further typed by PCR-SBT using 19 pairs of genotype-specific primers. Using this method, 17 different HR-HPV genotypes were identified. The most frequently observed HPV genotypes were HPV16 (44.0%, 73/166), 53 (28.9%, 48/166), 52 (25.3%, 42/166), 58 (22.3%, 37/166) and 35 (17.5%, 29/166). The proportions of single and multiple infections in the HPV-positive specimens were 34.9% and 65.1%, respectively. Multiple HPV types were most prevalent in the inflammatory state (63.0%), followed by cervical cancer (24.1%), CINI (11.1%), and CINII-III (1.9%). The results of our data analyses suggested that i) multiple HPV infection is not necessarily correlated with the severity of cervical abnormalities; and ii) among the multiple HPV infections, double infections combined with HPV16 is the most common. In addition, L1 full-length sequences of the top five high-risk HPV genotypes were amplified and sequenced. According to the L1 sequence of the epidemic genotypes that were amplified, we found that these

  3. p16 immunohistochemistry in oropharyngeal squamous cell carcinoma: a comparison of antibody clones using patient outcomes and high-risk human papillomavirus RNA status.

    PubMed

    Shelton, Jeremy; Purgina, Bibianna M; Cipriani, Nicole A; Dupont, William D; Plummer, Dale; Lewis, James S

    2017-09-01

    High-risk human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas have a more favorable prognosis than HPV-negative ones. p16 immunohistochemistry has been recommended as a prognostic test in clinical practice. Several p16 antibodies are available, and their performance has not been directly compared. We evaluated three commercially available p16 antibody clones (E6H4, JC8 and G175-405) utilizing 199 cases of oropharyngeal squamous cell carcinoma from a tissue microarray, read by three pathologists with three different cutoffs for positivity: any staining, >50% and >75%. Positive predictive values for high-risk HPV status by RNA in situ hybridization for the E6H4, JC8 and G175-405 clones were 98%, 100% and 99% at the 75% cutoff, but negative predictive values were much more variable at 86%, 69% and 56%, respectively. These improved using the 50% cutoff, becoming similar for all three antibodies. Intensity varied substantially, with 85% of E6H4, 72% of JC8 and 67% of G175-405 showing strong (3+) intensity. With Kaplan-Meier survival plots at the 75% cutoff, the E6H4 clone showed the largest differential in disease specific and overall survival between p16-positive and -negative results. Decreasing the cutoff to 50% increased correlation with HPV in situ hybridization and improved the survival differential for the JC8 and G175-405 clones without worsening of performance for the E6H4 clone. Interobserver agreement was also assessed by kappa scores and was highest for the E6H4 clone. Overall, these study results show modest but important performance differences between the three different p16 antibody clones, suggesting that the E6H4 clone performs best because of strongest staining intensity, greatest differential in outcomes between positive and negative results, lowest interobserver variability, and lowest background, nonspecific staining. The results also suggest that a 75% cutoff is very functional but that, in this patient population with high

  4. Human papillomavirus molecular biology.

    PubMed

    Harden, Mallory E; Munger, Karl

    Human papillomaviruses are small DNA viruses with a tropism for squamous epithelia. A unique aspect of human papillomavirus molecular biology involves dependence on the differentiation status of the host epithelial cell to complete the viral lifecycle. A small group of these viruses are the etiologic agents of several types of human cancers, including oral and anogenital tract carcinomas. This review focuses on the basic molecular biology of human papillomaviruses. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Post-Transcriptional Regulation of KLF4 by High-Risk Human Papillomaviruses Is Necessary for the Differentiation-Dependent Viral Life Cycle.

    PubMed

    Gunasekharan, Vignesh Kumar; Li, Yan; Andrade, Jorge; Laimins, Laimonis A

    2016-07-01

    Human papillomaviruses (HPVs) are epithelial tropic viruses that link their productive life cycles to the differentiation of infected host keratinocytes. A subset of the over 200 HPV types, referred to as high-risk, are the causative agents of most anogenital malignancies. HPVs infect cells in the basal layer, but restrict viral genome amplification, late gene expression, and capsid assembly to highly differentiated cells that are active in the cell cycle. In this study, we demonstrate that HPV proteins regulate the expression and activities of a critical cellular transcription factor, KLF4, through post-transcriptional and post-translational mechanisms. Our studies show that KLF4 regulates differentiation as well as cell cycle progression, and binds to sequences in the upstream regulatory region (URR) to regulate viral transcription in cooperation with Blimp1. KLF4 levels are increased in HPV-positive cells through a post-transcriptional mechanism involving E7-mediated suppression of cellular miR-145, as well as at the post-translational level by E6-directed inhibition of its sumoylation and phosphorylation. The alterations in KLF4 levels and functions results in activation and suppression of a subset of KLF4 target genes, including TCHHL1, VIM, ACTN1, and POT1, that is distinct from that seen in normal keratinocytes. Knockdown of KLF4 with shRNAs in cells that maintain HPV episomes blocked genome amplification and abolished late gene expression upon differentiation. While KLF4 is indispensable for the proliferation and differentiation of normal keratinocytes, it is necessary only for differentiation-associated functions of HPV-positive keratinocytes. Increases in KLF4 levels alone do not appear to be sufficient to explain the effects on proliferation and differentiation of HPV-positive cells indicating that additional modifications are important. KLF4 has also been shown to be a critical regulator of lytic Epstein Barr virus (EBV) replication underscoring the

  6. Post-Transcriptional Regulation of KLF4 by High-Risk Human Papillomaviruses Is Necessary for the Differentiation-Dependent Viral Life Cycle

    PubMed Central

    Gunasekharan, Vignesh Kumar; Li, Yan; Laimins, Laimonis A.

    2016-01-01

    Human papillomaviruses (HPVs) are epithelial tropic viruses that link their productive life cycles to the differentiation of infected host keratinocytes. A subset of the over 200 HPV types, referred to as high-risk, are the causative agents of most anogenital malignancies. HPVs infect cells in the basal layer, but restrict viral genome amplification, late gene expression, and capsid assembly to highly differentiated cells that are active in the cell cycle. In this study, we demonstrate that HPV proteins regulate the expression and activities of a critical cellular transcription factor, KLF4, through post-transcriptional and post-translational mechanisms. Our studies show that KLF4 regulates differentiation as well as cell cycle progression, and binds to sequences in the upstream regulatory region (URR) to regulate viral transcription in cooperation with Blimp1. KLF4 levels are increased in HPV-positive cells through a post-transcriptional mechanism involving E7-mediated suppression of cellular miR-145, as well as at the post-translational level by E6–directed inhibition of its sumoylation and phosphorylation. The alterations in KLF4 levels and functions results in activation and suppression of a subset of KLF4 target genes, including TCHHL1, VIM, ACTN1, and POT1, that is distinct from that seen in normal keratinocytes. Knockdown of KLF4 with shRNAs in cells that maintain HPV episomes blocked genome amplification and abolished late gene expression upon differentiation. While KLF4 is indispensable for the proliferation and differentiation of normal keratinocytes, it is necessary only for differentiation-associated functions of HPV-positive keratinocytes. Increases in KLF4 levels alone do not appear to be sufficient to explain the effects on proliferation and differentiation of HPV-positive cells indicating that additional modifications are important. KLF4 has also been shown to be a critical regulator of lytic Epstein Barr virus (EBV) replication underscoring the

  7. Comparative performance of novel self-sampling methods in detecting high-risk human papillomavirus in 30,130 women not attending cervical screening.

    PubMed

    Bosgraaf, Remko P; Verhoef, Viola M J; Massuger, Leon F A G; Siebers, Albert G; Bulten, Johan; de Kuyper-de Ridder, Gabriëlle M; Meijer, Chris J M; Snijders, Peter J F; Heideman, Daniëlle A M; IntHout, Joanna; van Kemenade, Folkert J; Melchers, Willem J G; Bekkers, Ruud L M

    2015-02-01

    We determined whether the participation rate for a brush-based cervicovaginal self-sampling device is noninferior to the participation rate for a lavage-based one for testing for hrHPV (high-risk human papillomavirus). Additionally, positivity rates for hrHPV, the detection rates for cervical intraepithelial neoplasia grades 2 and 3 or worse (CIN2+/3+), and user comfort were compared. A total of 35,477 non-responders of the regular cervical screening program aged 33-63 years were invited to participate. Eligible women (n = 30,130) were randomly assigned to receive either a brush-based or a lavage-based device, and a questionnaire for reporting user convenience. Self-sampling responders testing hrHPV-positive were invited for a physician-taken sample for cytology; triage-positive women were referred for colposcopy. A total of 5,218 women participated in the brush-based sampling group (34.6%) and 4809 women in the lavage-based group (31.9%), i.e. an absolute difference of 2.7% (95%CI 1.8-4.2). The hrHPV-positivity rates in the two groups were identical (8.3%, relative risk (RR) 0.99, 95%CI 0.87-1.13). The detection of CIN2+ and CIN3+ in the brush group (2.0% for CIN2+; 1.3% for CIN3+) was similar to that in the lavage group (1.9% for CIN2+; 1.0% for CIN3+) with a cumulative RR of 1.01, 95%CI 0.83-1.24 for CIN2+ and 1.25, 95%CI 0.92-1.70 for CIN3+. The two self-sampling devices performed similarly in user comfort. In conclusion, offering a brush-based device to non-responders is noninferior to offering a lavage-based device in terms of participation. The two self-sampling methods are equally effective in detecting hrHPV, CIN2+/CIN3+ and are both well accepted. © 2014 UICC.

  8. The High-Risk Human Papillomavirus E6 Oncogene Exacerbates the Negative Effect of Tryptophan Starvation on the Development of Chlamydia trachomatis

    PubMed Central

    Sherchand, Shardulendra P.; Ibana, Joyce A.; Zea, Arnold H.; Quayle, Alison J.; Aiyar, Ashok

    2016-01-01

    Chlamydia trachomatis is an obligate intracellular pathogen that requires specific essential nutrients from the host cell, one of which is the amino acid tryptophan. In this context interferon gamma (IFNγ) is the major host protective cytokine against chlamydial infections because it induces the expression of the host enzyme, indoleamine 2,3-dioxygenase 1, that degrades tryptophan, thereby restricting bacterial replication. The mechanism by which IFNγ acts has been dissected in vitro using epithelial cell-lines such as HeLa, HEp-2, or the primary-like endocervical cell-line A2EN. All these cell-lines express the high-risk human papillomavirus oncogenes E6 & E7. While screening cell-lines to identify those suitable for C. trachomatis co-infections with other genital pathogens, we unexpectedly found that tryptophan starvation did not completely block chlamydial development in cell-lines that were HR-HPV negative, such as C33A and 293. Therefore, we tested the hypothesis that HR-HPV oncogenes modulate the effect of tryptophan starvation on chlamydial development by comparing chlamydial development in HeLa and C33A cell-lines that were both derived from cervical carcinomas. Our results indicate that during tryptophan depletion, unlike HeLa, C33A cells generate sufficient intracellular tryptophan via proteasomal activity to permit C. trachomatis replication. By generating stable derivatives of C33A that expressed HPV16 E6, E7 or E6 & E7, we found that E6 expression alone was sufficient to convert C33A cells to behave like HeLa during tryptophan starvation. The reduced tryptophan levels in HeLa cells have a biological consequence; akin to the previously described effect of IFNγ, tryptophan starvation protects C. trachomatis from clearance by doxycycline in HeLa but not C33A cells. Curiously, when compared to the known Homo sapiens proteome, the representation of tryptophan in the HR-HPV E6 & E6AP degradome is substantially lower, possibly providing a mechanism that

  9. 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 Central

    Constantinidis, Theocharis; Constantinidis, Theodoros C.

    2015-01-01

    Objectives 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. Methods 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. Results 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). Conclusion 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

  10. Incidence and clearance of anal high-risk human papillomavirus in HIV-positive men who have sex with men: estimates and risk factors

    PubMed Central

    Geskus, Ronald B.; González, Cristina; Torres, Montserrat; Del Romero, Jorge; Viciana, Pompeyo; Masiá, Mar; Blanco, José R.; Iribarren, Mauricio; De Sanjosé, Silvia; Hernández-Novoa, Beatriz; Ortiz, Marta; Del Amo, Julia

    2016-01-01

    Background: To estimate incidence and clearance of high-risk human papillomavirus (HR-HPV), and their risk factors, in men who have sex with men (MSM) recently infected by HIV in Spain; 2007–2013. Methods: Multicenter cohort. HR-HPV infection was determined and genotyped with linear array. Two-state Markov models and Poisson regression were used. Results: We analysed 1570 HR-HPV measurements of 612 MSM over 13 608 person-months (p-m) of follow-up. Median (mean) number of measurements was 2 (2.6), median time interval between measurements was 1.1 years (interquartile range: 0.89–1.4). Incidence ranged from 9.0 [95% confidence interval (CI) 6.8–11.8] per 1000 p-m for HPV59 to 15.9 (11.7–21.8) per 1000 p-m for HPV51. HPV16 and HPV18 had slightly above average incidence: 11.9/1000 p-m and 12.8/1000 p-m. HPV16 showed the lowest clearance for both ‘prevalent positive’ (15.7/1000 p-m; 95% CI 12.0–20.5) and ‘incident positive’ infections (22.1/1000 p-m; 95% CI 11.8–41.1). More sexual partners increased HR-HPV incidence, although it was not statistically significant. Age had a strong effect on clearance (P-value < 0.001) due to the elevated rate in MSM under age 25; the effect of HIV-RNA viral load was more gradual, with clearance rate decreasing at higher HIV-RNA viral load (P-value 0.008). Conclusion: No large variation in incidence by HR-HPV type was seen. The most common incident types were HPV51, HPV52, HPV31, HPV18 and HPV16. No major variation in clearance by type was observed, with the exception of HPV16 which had the highest persistence and potentially, the strongest oncogenic capacity. Those aged below 25 or with low HIV-RNA- viral load had the highest clearance. PMID:26355673

  11. [Expression and significance of P16INK4A and PTEN in high-risk human papillomavirus-related cervical cancer].

    PubMed

    Zhao, Xian-Lan; Cheng, Shu-Xia; Kong, Xiang-Dong

    2007-05-01

    High-risk human papillomavirus (HR-HPV) is the most important etiologic factor for cervical cancer. Recent studies have revealed that abnormal expression of tumor suppressor gene P16INK4A is closely associated with HR-HPV infection during carcinogenesis of cervical epithelium. Tumor suppressor gene PTEN is also involved in cervical tumorigenesis. This study was to investigate the correlations of HR-HPV infection to P16INK4A and PTEN expression and its clinical significance in the carcinogenesis of cervical epithelium. The expression of P16INK4A and PTEN in 30 specimens of normal cervical tissues, 11 specimens of cancer in situ (CIS), and 24 specimens of invasive cervical carcinoma (ICC) was detected by SP immunohistochemistry; 13 types of HR-HPV DNA in these cases were detected by Hybrid Capture 2 (HC-2) assay. The positive rates of HR-HPV and P16INK4A were significantly higher in ICC and CIS than in normal tissues (91.7% and 90.9% vs. 30.0%, P<0.001; 87.5% and 81.8% vs. 6.7%, P<0.001). Both HR-HPV DNA and P16INK4A overexpression (moderate or strong expression) were observed simultaneously in 21 specimens of ICC and 9 specimens of CIS; they were simultaneously negative in 20 specimens of normal cervical tissues and 1 specimen of CIS and 2 specimens of ICC. Overexpression of P16INK4A was positively correlated to HR-HPV infection in cervical cancer (rs = 0.690, P<0.001). PTEN was moderately or strongly expressed in 26 specimens of normal cervical tissues. The positive rate of PTEN was significantly lower in ICC and CIS than in normal cervical tissues (37.5% and 36.4% vs. 83.3%, P<0.01). No obvious relationship between PTEN and HR-HPV was found (rs = -0.174, P = 0.167). P16INK4A is overexpressed in HR-HPV-infected cervical cancer, but its tumor suppressor action might be inhibited. In contrast, the functional down-regulation of PTEN contributes to cervical tumorigenesis through HR-HPV-independent mechanism.

  12. [Association between life style, diet intake and high risk-human papillomavirus persistent infection among rural women in Xinmi City, Henan Province].

    PubMed

    Lei, Xiaoqin; Chen, Wen; Yu, Lulu; Wu, Zeni; Qin, Yu; Gao Guoqi; Zheng, Fengxian; Li, Caihong; Lian, Xuemei

    2016-01-01

    To explore the association between life style, diet intake and high risk human papillomavirus (HR-HPV) persistent infection among Chinese rural women living in Xinmi City, Henan Province. In 2010, a 3-year prospective study in which 2500 women were enrolled and screened by different HR-HPV DNA tests was conducted, part of women among them was followed and tested for HR-HPV DNA in 2012 and 2014. Furthermore, socio demographic factors, gynecological information and diet intake in the past 12 months were collected by self-designed questionnaire in 2014. A total of 721 women with complete test results were eligible for the final analysis. Study participants were divided into 3 groups (persistent infection group, transient infection group, and negative group) by HR-HPV status, and the association between life style, diet intake and HR-HPV persistence was evaluated using ordinal logistic regression model. The average age of 721 women included in the analysis was 50 years old. 141 women had HR-HPV persistent infection, 180 women had HR-HPV transient infection, and 400 women were negative for HR-HPV in 3 years. Age (Χ2 = 58.449, P < 0.001, P(trend) < 0.001), smoking (Χ2 = 6.981, P = 0.021), contraception method (Χ2 = 8.448, P = 0.015) , menopause (Χ2 = 35.712, P < 0.001), number of live births (Χ2 = 16.340, P < 0.001, P(trend) < 0.001), and the intake frequency of cereals (Χ2 = 17.937, P = 0.001) or others (Χ2 = 12.107, P = 0.017) varied significantly between women grouped by different HR-HPV status. Compared to women who were older than 59 years, women in the younger groups had a much lower risk of HR-HPV persistence (adjusted OR1 = 0.39, 95% CI 0.26 - 0.59, OR2 = 0.40, 95% CI 0.23 - 0.69, and OR3 = 0.28, 95% CI 0.12 - 0.68). Age is the main risk factor of HR-HPV persistent infection. Lifestyle, diet intake do not associate with HR-HPV persistence after adjustment by age.

  13. Previous cervical cytology and high-risk human papillomavirus testing in a cohort of patients with invasive cervical carcinoma in Shandong Province, China

    PubMed Central

    Wang, Xinguo; Peng, Dezhi; Bi, Chunrui; Jiang, Lingbo; Zhao, Dongman; Tian, Xinxin

    2017-01-01

    Background Currently, available data regarding previous cervical cytology and high-risk human papillomavirus (hrHPV) test results to detect invasive cervical cancer are limited and controversial in China. Therefore, this retrospective study in a population of Chinese women with invasive cervical carcinoma aimed to gain further insight into the roles of cytology and hrHPV testing in cervical cancer screening. Methods A total of 1214 cases with a histological diagnosis of invasive cervical cancer were retrieved from the Pathology Database of Jinan KingMed Diagnostics (JKD) over a 5-year period. Previous cytology and hrHPV test results of 469 patients carried out within the year before cancer diagnosis were documented. Results A higher percentage of patients who had undergone prior screening had micro-invasive cervical carcinoma than patients who had no prior screening (25.4% vs. 12.1%, P < 0.001). Of the 469 patients with available prior screening results, 170 had cytology alone, 161 had hrHPV testing alone, and 138 had both cytology and hrHPV testing. There was a significantly lower percentage of hrHPV-positive cases with adenocarcinoma than with squamous cell carcinoma (77.8% vs. 96.4%, P = 0.001). The hrHPV test showed a significantly higher sensitivity than cytology alone (94.4% vs. 85.3%, P = 0.006). The overall sensitivity of the combination of cytology and hrHPV testing (98.6%) was much higher than that of cytology alone (P < 0.001) but only marginally higher than that of hrHPV testing alone (P = 0.058). Conclusions The results revealed that prior cervical screening can detect a significantly larger number of micro-invasive cervical cancers. The hrHPV test can provide a more sensitive and efficient strategy than cytology alone. As the addition of cytology to hrHPV testing can only marginally increase the efficiency of the hrHPV test, hrHPV testing should be used as the primary screening approach, especially in the low-resource settings of China. PMID:28662160

  14. Incidence and clearance of anal high-risk human papillomavirus in HIV-positive men who have sex with men: estimates and risk factors.

    PubMed

    Geskus, Ronald B; González, Cristina; Torres, Montserrat; Del Romero, Jorge; Viciana, Pompeyo; Masiá, Mar; Blanco, José R; Iribarren, Mauricio; De Sanjosé, Silvia; Hernández-Novoa, Beatriz; Ortiz, Marta; Del Amo, Julia

    2016-01-02

    To estimate incidence and clearance of high-risk human papillomavirus (HR-HPV), and their risk factors, in men who have sex with men (MSM) recently infected by HIV in Spain; 2007-2013. Multicenter cohort. HR-HPV infection was determined and genotyped with linear array. Two-state Markov models and Poisson regression were used. We analysed 1570 HR-HPV measurements of 612 MSM over 13 608 person-months (p-m) of follow-up. Median (mean) number of measurements was 2 (2.6), median time interval between measurements was 1.1 years (interquartile range: 0.89-1.4). Incidence ranged from 9.0 [95% confidence interval (CI) 6.8-11.8] per 1000 p-m for HPV59 to 15.9 (11.7-21.8) per 1000 p-m for HPV51. HPV16 and HPV18 had slightly above average incidence: 11.9/1000 p-m and 12.8/1000 p-m. HPV16 showed the lowest clearance for both 'prevalent positive' (15.7/1000 p-m; 95% CI 12.0-20.5) and 'incident positive' infections (22.1/1000 p-m; 95% CI 11.8-41.1). More sexual partners increased HR-HPV incidence, although it was not statistically significant. Age had a strong effect on clearance (P-value < 0.001) due to the elevated rate in MSM under age 25; the effect of HIV-RNA viral load was more gradual, with clearance rate decreasing at higher HIV-RNA viral load (P-value 0.008). No large variation in incidence by HR-HPV type was seen. The most common incident types were HPV51, HPV52, HPV31, HPV18 and HPV16. No major variation in clearance by type was observed, with the exception of HPV16 which had the highest persistence and potentially, the strongest oncogenic capacity. Those aged below 25 or with low HIV-RNA- viral load had the highest clearance.

  15. Genital human papillomavirus infection.

    PubMed Central

    Lowy, D R; Kirnbauer, R; Schiller, J T

    1994-01-01

    Genital human papillomavirus (HPV) infection is a common sexually transmitted disease that at the present time is not effectively controlled or treated. Many infections are inapparent and transient. However, some HPV infections result in persistent lesions that in some cases undergo carcinogenic progression. A subset of genital HPVs, designated high-risk types, are preferentially associated with high-grade dysplasias and carcinomas. About 90% of cervical cancers contain high-risk HPV DNA, most often HPV16. Development of a subunit vaccine against high-risk genital HPVs is a desirable and, it appears, an increasingly feasible long-term goal. The viral E6 and E7 oncoproteins are selectively maintained and expressed in progressed HPV tumors and could potentially be targets for therapeutic vaccines. The L1 major virion structural proteins have recently been shown to self-assemble into virus-like particles when expressed in insect cells. These particles might serve as the basis for a prophylactic vaccine to prevent genital HPV infection. Images PMID:8146136

  16. Serum immunoglobulin A response to human papillomavirus type 16 virus-like particles in human immunodeficiency virus (HIV)-positive and high-risk HIV-negative women.

    PubMed

    Viscidi, Raphael P; Ahdieh-Grant, Linda; Schneider, Michael F; Clayman, Barbara; Massad, L Stewart; Anastos, Kathryn M; Burk, Robert D; Minkoff, Howard; Palefsky, Joel; Levine, Alexandra; Strickler, Howard

    2003-12-15

    Serum samples from 2008 human immunodeficiency virus (HIV)-positive and 551 HIV-negative women were tested for immunoglobulin A (IgA) to human papillomavirus (HPV) type 16 capsids. IgA seropositivity was lower than previously reported IgG seropositivity (7% vs. 51%), but, like IgG antibodies, HPV 16 IgA was associated with sexual behavior, cervicovaginal HPV 16 DNA, and cytological abnormalities. IgA seropositivity was higher in HIV-positive women than in HIV-negative women (7.7% vs. 4.9%; P=.02), but the association was lost after adjustment for HPV 16 cervicovaginal infection. IgA, but not IgG, seropositivity was associated with progression to high-grade cytological abnormalities (relative hazard [RH], 2.2 [95% confidence interval, 1.2-4.2]), raising the possibility that an IgA response to HPV 16, as described for other DNA viruses, may be a marker of persistent viral replication. The risk of incident infection with non-16-related HPV types was increased in IgA seropositive women (RH, 1.8 [95% confidence interval, 1.3-2.6]), compared with seronegative women (RH, 2.2 [95% confidence interval, 0.9-5.4]), but there was no difference in the risk of incident HPV 16 or HPV 16-related infections. This may be evidence of partial type-specific or clade-specific immunity conferred by seropositivity to HPV 16 capsids.

  17. Vaccination against human papillomavirus

    PubMed Central

    Mello, Claudia Figueiredo

    2013-01-01

    ABSTRACT Human papillomavirus infection is common and causes different manifestations. This infection is a public health concern because it has been associated with genital tract malignant diseases among men and women. Currently two vaccines are available to prevent the human papillomavirus infection and its associated diseases. PMID:24488402

  18. Effect of Glacial Acetic Acid Treatment of Liquid-Based Cytology Collections on Performance of Cervista HPV HR for Detection of High-Risk Human Papillomavirus

    PubMed Central

    Du Chateau, Brian K.; Nelson, Bridget E.; Griep, Judith; Czarnecka, Jolanta; Amrhein, Robert D.; Schroeder, Elizabeth R.

    2012-01-01

    Inadequate cervical cytological analysis can be facilitated by glacial acetic acid (GAA) treatment of primary liquid-based collections to remove mucus, erythrocytes, inflammatory cells, and cellular debris. In the context of a commercial human papillomavirus (HPV) hybridization assay performed on 465 tandem specimens with and without GAA treatment, we show that GAA treatment significantly reduces genomic DNA content (P < 0.0001) and creates an increased potential for indeterminate and false-negative results. In the context of cytological workflow, laboratories should consider providing a specimen aliquot for HPV DNA detection prior to GAA treatment. PMID:22442317

  19. Effect of glacial acetic acid treatment of liquid-based cytology collections on performance of Cervista HPV HR for detection of high-risk human papillomavirus.

    PubMed

    Munson, Erik; Du Chateau, Brian K; Nelson, Bridget E; Griep, Judith; Czarnecka, Jolanta; Amrhein, Robert D; Schroeder, Elizabeth R

    2012-06-01

    Inadequate cervical cytological analysis can be facilitated by glacial acetic acid (GAA) treatment of primary liquid-based collections to remove mucus, erythrocytes, inflammatory cells, and cellular debris. In the context of a commercial human papillomavirus (HPV) hybridization assay performed on 465 tandem specimens with and without GAA treatment, we show that GAA treatment significantly reduces genomic DNA content (P < 0.0001) and creates an increased potential for indeterminate and false-negative results. In the context of cytological workflow, laboratories should consider providing a specimen aliquot for HPV DNA detection prior to GAA treatment.

  20. Human papillomaviruses and cancer.

    PubMed

    Haedicke, Juliane; Iftner, Thomas

    2013-09-01

    Human papillomaviruses (HPV) are small oncogenic DNA viruses of which more than 200 types have been identified to date. A small subset of these is etiologically linked to the development of anogenital malignancies such as cervical cancer. In addition, recent studies established a causative relationship between these high-risk HPV types and tonsillar and oropharyngeal cancer. Clinical management of cervical cancer and head and neck squamous cell carcinomas (HNSCCs) is largely standardized and involves surgical removal of the tumor tissue as well as adjuvant chemoradiation therapy. Notably, the response to therapeutic intervention of HPV-positive HNSCCs has been found to be better as compared to HPV-negative tumors. Although the existing HPV vaccine is solely licensed for the prevention of cervical cancer, it might also have prophylactic potential for the development of high-risk HPV-associated HNSCCs. Another group of viruses, which belongs to the beta-HPV subgroup, has been implicated in nonmelanoma skin cancer, however, the etiology remains to be established. Treatment of HPV-induced nonmelanoma skin cancer is based on local excision. However, topically applied immune-modulating substances represent non-surgical alternatives for the management of smaller cutaneous tumors. In this review we present the current knowledge of the role of HPV in cancer development and discuss clinical management options as well as targets for the development of future intervention therapies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. Human papillomaviruses-related cancers

    PubMed Central

    Al Moustafa, Ala-Eddin; Al-Awadhi, Rana; Missaoui, Nabiha; Adam, Ishag; Durusoy, Raika; Ghabreau, Lina; Akil, Nizar; Ahmed, Hussain Gadelkarim; Yasmeen, Amber; Alsbeih, Ghazi

    2014-01-01

    Human papillomavirus (HPV) infections are estimated to be the most common sexually transmitted infections worldwide. Meanwhile, it is well established that infection by high-risk HPVs is considered the major cause of cervical cancer since more than 96% of these cancers are positive for high-risk HPVs, especially types 16 and 18. Moreover, during the last 2 decades, numerous studies pointed-out the possible involvement of high-risk HPV in several human carcinomas including head and neck, colorectal and breast cancers. The association between high-risk HPVs and cervical cancer and potentially other human malignancies would necessitate the introduction of vaccines which were generated against the 2 most frequent high-risk HPVs (types 16 and 18) worldwide, including the Middle East (ME) as well as North African countries. The presence of high-risk HPVs in the pathogenesis of human cancers in the ME, which is essential in order to evaluate the importance of vaccination against HPVs, has not been fully investigated yet. In this review, we present an overview of the existing epidemiological evidence regarding the presence of HPV in human cancers in the ME and the potential impact of vaccination against HPV infections and its outcome on human health in this region. PMID:25424787

  2. Human Papillomavirus (HPV) Vaccines

    MedlinePlus

    ... Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training at ... of Cancer, 1975-2009, featuring the burden and trends in human papillomavirus (HPV)-associated cancers and HPV ...

  3. Carcinogenic human papillomavirus infection.

    PubMed

    Schiffman, Mark; Doorbar, John; Wentzensen, Nicolas; de Sanjosé, Silvia; Fakhry, Carole; Monk, Bradley J; Stanley, Margaret A; Franceschi, Silvia

    2016-12-01

    Infections with human papillomavirus (HPV) are common and transmitted by direct contact. Although the great majority of infections resolve within 2 years, 13 phylogenetically related, sexually transmitted HPV genotypes, notably HPV16, cause - if not controlled immunologically or by screening - virtually all cervical cancers worldwide, a large fraction of other anogenital cancers and an increasing proportion of oropharyngeal cancers. The carcinogenicity of these HPV types results primarily from the activity of the oncoproteins E6 and E7, which impair growth regulatory pathways. Persistent high-risk HPVs can transition from a productive (virion-producing) to an abortive or transforming infection, after which cancer can result after typically slow accumulation of host genetic mutations. However, which precancerous lesions progress and which do not is unclear; the majority of screening-detected precancers are treated, leading to overtreatment. The discovery of HPV as a carcinogen led to the development of effective preventive vaccines and sensitive HPV DNA and RNA tests. Together, vaccination programmes (the ultimate long-term preventive strategy) and screening using HPV tests could dramatically alter the landscape of HPV-related cancers. HPV testing will probably replace cytology-based cervical screening owing to greater reassurance when the test is negative. However, the effective implementation of HPV vaccination and screening globally remains a challenge.

  4. [Human papillomavirus prophylactic vaccine].

    PubMed

    Kawana, Kei

    2012-06-01

    Human papillomavirus causes viral-dependent cancers, including cervical, anal, vulvar, penile, vaginal, and oropharyngeal, and condyloma acuminata. In the last decade, HPV prophylactic vaccine has been developed and spread worldwide after many large-scale clinical studies. These studies demonstrate significant clinical efficacy for prevention of HPV16/18/6/11-related diseases. In particular, prevention of cervical cancer should be the most important role in the world. In Japan, incidence of cervical cancer does not increase, but the peak of age of the patients at 2005 is 25-45 years old and became 20 years younger than that at 1985. The current two HPV vaccines can prevent the infection of HPV16/18 among high-risk HPVs and will provide a significant impact especially on young-age onset cervical cancer. Furthermore, quadrivalent HPV vaccine, Gardasil, has shown population impact that is decrease of patients with condyloma acuminate in several countries. The clinical efficacy seems to be convincing. Here HPV vaccine will be reviewed based on the literatures.

  5. Comparison of the Third Wave Invader Human Papillomavirus (HPV) Assay and the Digene HPV Hybrid Capture 2 Assay for Detection of High-Risk HPV DNA▿

    PubMed Central

    Ginocchio, C. C.; Barth, D.; Zhang, F.

    2008-01-01

    This study compared the clinical performance of the Digene Hybrid Capture 2 (HC2) assay to that of a prototype Third Wave Invader human papillomavirus (HPV) (IHPV) analyte-specific reagent-based assay for the detection of oncogenic or “high-risk” (HR) HPV DNA using liquid-based cytology specimens. In total, 821 ThinPrep vials were tested using both assays. In accordance with the type-specific probes contained within each test, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the IHPV assay were 95.9%, 97.6%, 97.5%, and 96.1%, respectively, and those for the HC2 assay were 98.1%, 86.2%, 87.1%, and 97.9%. Overall, the sensitivity and NPV were comparable between the assays, but the IHPV assay demonstrated a better specificity and PPV, since the IHPV assay had fewer false-positive HR HPV results. The incorporation of an internal control to evaluate the cellularity of the test material is an important feature of the IHPV assay and should reduce the risk of false-negative results due to insufficient sample collection rather than the lack of HR HPV DNA. An additional benefit of the IHPV assay was the smaller sample volume required (1 ml versus 4 ml for the HC2 assay). PMID:18367578

  6. Prevalence of high-risk human papillomavirus type 16 and 18 in oral and cervical cancers in population from Gujarat, West India.

    PubMed

    Patel, Kinjal R; Vajaria, Bhairavi N; Begum, Rasheedunnisa; Desai, Ava; Patel, Jayendra B; Shah, Franky D; Shukla, Shilin N; Patel, Prabhudas S

    2014-04-01

    Oral and cervical cancers are major malignancies in men and women, respectively, in India. This study evaluated occurrence of human papillomavirus (HPV) 16 and 18 infections in oral and cervical cancers to estimate HPV-associated burden of these cancers in the population from Gujarat, West India. A total of 97 malignant oral carcinoma tissues and 52 cervical carcinoma tissues were analyzed by type-specific PCR for the presence of HPV type 16 and 18 infections. None of the oral cancer patients revealed the presence of HPV type 16 and 18 infection. In cervical cancer, 31 (59.6%) patients were infected with HPV 16 and 18. Of these 31 HPV-positive cervical cancer patients, 28 (90.3%) were infected with HPV 16 and 3 (9.7%) were infected with HPV 18. The results suggested that HPV 16 and 18 do not play an important role in oral carcinogenesis in the population from Gujarat, West India. However, HPV 16 is highly prevalent in the cervical cancer patients, which may be considered for planning of prevention programs such as screening and vaccination in women from this region. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Tobacco Smoke Activates Human Papillomavirus 16 p97 Promoter and Cooperates with High-Risk E6/E7 for Oxidative DNA Damage in Lung Cells

    PubMed Central

    Muñoz, Juan P.; Chnaiderman, Jonás; Urzúa, Ulises; León, Oscar; Tornesello, Maria L.; Corvalán, Alejandro H.; Soto-Rifo, Ricardo; Aguayo, Francisco

    2015-01-01

    We have previously shown a functional interaction between human papillomavirus type 16 (HPV-16) E6 and E7 oncoproteins and cigarette smoke condensate (CSC) in lung cells suggesting cooperation during carcinogenesis. The molecular mechanisms of such interaction, however, remain to be elucidated. Here we first present evidence showing that cigarette smoke condensate (CSC) has the ability to activate the HPV-16 p97 promoter by acting on the long control region (LCR) in lung epithelial cells. Interestingly, we observed that CSC-induced p97 promoter activation occurs in a dose-dependent manner in both tumor A-549 (lung adenocarcinoma), H-2170 (bronchial carcinoma), SiHa or Hela (cervical carcinoma) cells but not in non-tumor BEAS-2B (bronchial) or NL-20 (alveolar) lung cells unless they ectopically expressed the HPV-16 E6 and E7 oncogenes. In addition, we also observed a significant increase of primary DNA damage in tumor and non-tumor CSC-treated lung cells expressing HPV-16 E6 and E7 oncogenes suggesting a cooperative effect in this process, even though the contribution of E7 was significantly higher. Taken together, our results strongly suggest that tobacco smoke is able to induce the activation of the HPV-16 p97 promoter in cooperation with HPV-16 E6 and E7 oncogenes that, in turn, sensitize lung cells to tobacco smoke-induced DNA damage. PMID:25830243

  8. The human papillomaviruses.

    PubMed

    Orth, G; Jablonska, S; Breitburd, F; Favre, M; Croissant, O

    1978-01-01

    Recent biochemical and serological studies have shown the existence of at least four distinct types of human papillomaviruses (HPVs) causing benign skin lesions. These viruses show hardly no antigenic relationships; their DNAs differ by their sensitivity to restriction endonucleases, and show little, if any, sequence homology, as detected by molecular hybridization using complementary RNAs transcribed in vitro. Data on the pathogenicity of HPVs are still incomplete but indicate that some types of benign skin lesions (plantar warts, common warts, flat warts) may be preferentially associated with some types of HPV. Most interesting is that epidermodysplasia verruciformis has been found associated with two types of virus, and that malignant conversion of some lesions has been observed in all the patients infected with one of them. This suggests that at least a HPV may have a higher oncogenic potential, as do rabbit (Shope) papillomavirus and bovine alimentary tract papillomavirus. Much remains to be known on human papilloma-viruses and further studies may lead to the characterization of additional types of HPVs, especially in genital condylomata acuminata and laryngeal papillomas whose malignant conversion, although rare, may be observed. Progress in this field has been and remains hampered by the lack of cell culture systems allowing replication of these highly host and tissue specific viruses, and by the widely variable virus content of the different human lesions known to be associated with a papillomavirus. Further studies are warranted by the possible role of these widespread and epitheliotropic viruses in the origin of some carcinomas in man.

  9. Papillomaviruses and human disease

    SciTech Connect

    Syrjanen, K.; Gissman, L.; Koss, L.G.

    1987-01-01

    This book contains 17 selections. Some of the titles are: Papillomaviruses: particles, genome organization and proteins; Physical state of papillomavirus DNA in tumors; Transforming and regulatory functions of bovine papillomavirus Type 1; and Transcription of papillomavirus genomes.

  10. Use of a high-risk human papillomavirus DNA test as the primary test in a cervical cancer screening programme: a population-based cohort study.

    PubMed

    Zorzi, M; Del Mistro, A; Farruggio, A; de'Bartolomeis, L; Frayle-Salamanca, H; Baboci, L; Bertazzo, A; Cocco, P; Fedato, C; Gennaro, M; Marchi, N; Penon, M G; Cogo, C; Ferro, A

    2013-09-01

    To present the results of the first 2 years of a human papillomavirus (HPV) test-based screening programme outside the research context. Population-based cohort study. A cervical service screening programme in Italy. Women aged 25-64 years invited to screening from April 2009 to April 2011. Eligible women were invited to undergo an HPV test: those with a negative HPV test went on to the next screening episode; those with a positive HPV went on to triage with a Pap smear. Women with positive cytology (i.e. positive for atypical squamous cells of undetermined significance or worse, ASC-US+) were referred to colposcopy, whereas those with negative cytology were referred to repeat HPV testing 1 year later. Participation rate, positivity at HPV and at triage, referral rate to colposcopy, positive predictive value for cervical intraepithelial neoplasia grade 2+ (CIN2+) at colposcopy, and detection rate for CIN2+. Participation increased compared with the previous Pap programme (60.6 versus 43.9%). The HPV positivity rate was 7.0; 39.6% of Pap smears were scored as positive, and therefore 2.8% of the women screened were referred for immediate colposcopy. The compliance of women who scored positive for HPV and negative for Pap for repeat HPV testing at 12 months was 78.6%, and the HPV positivity rate was 56.6%. The overall referral rate to colposcopy was 4.6%. The overall detection rate for CIN2+ was 4.5 versus 1.5% of the Pap programme (25-34 years, 8.2%; 35+ years, 3.6%). Compared with the traditional Pap test, the HPV programme recorded a higher response to invitation and an increased DR for CIN2+. The most critical aspects were the reading of cytology in women that were positive for HPV and the increased workload at colposcopy. © 2013 RCOG.

  11. High-risk human papillomavirus is sexually transmitted: evidence from a follow-up study of virgins starting sexual activity (intercourse).

    PubMed

    Kjaer, S K; Chackerian, B; van den Brule, A J; Svare, E I; Paull, G; Walbomers, J M; Schiller, J T; Bock, J E; Sherman, M E; Lowy, D R; Meijer, C L

    2001-02-01

    Genital human papillomavirus (HPV) infection is generally considered to be sexually transmitted. However, nonsexual spread of the virus has also been suggested. The goal of this study was to assess: (a) the role of sexual intercourse in the transmission of HPV; (b) the determinants for seroconversion; and (c) the correlation between HPV DNA, abnormal cervical cytology, and serological response to HPV16. One hundred virgins and 105 monogamous women were randomly selected from a population-based cohort study in Copenhagen, Denmark, in which the women were examined twice with 2-year interval (interview, cervical swabs, Pap smear, blood samples). The presence of HPV DNA was determined by GP5+/6+ primers based HPV-PCR-EIA. HPV 16 virus-like particles (VLP) antibodies were detected by ELISA. All of the virgins were both HPV DNA negative and seronegative to VLP16, except for one woman who was weakly HPV 6 DNA positive. Only those virgins who initiated sexual activity became HPV DNA positive and/or VLP16 positive. The most important determinant of HPV DNA acquisition was the number of partners between the two examinations. The only significant risk factor for HPV 16 VLP seroconversion among women acquiring HPV DNA was HPV type. Our results show that sexual intercourse is important in the transmission of HPV, and that HPV 16 VLP seroconversion and the development of cervical lesions only occur after HPV transmission. Remarkably, no cervical lesions were found in HPV 16 DNA positive women who had seroconverted. Although based on small numbers, this may suggest that the development of antibodies had a protective effect.

  12. 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

  13. Candidate Soluble Immune Mediators in Young Women with High-Risk Human Papillomavirus Infection: High Expression of Chemokines Promoting Angiogenesis and Cell Proliferation

    PubMed Central

    Zanotta, Nunzia; Tornesello, Maria Lina; Annunziata, Clorinda; Stellato, Giovanni; Buonaguro, Franco Maria; Comar, Manola

    2016-01-01

    Background The causal interpretation of cervical immune response to Human Papillomavirus (HPV) infection is complex and poorly characterized mainly due to the delicate balance that exists between viral infection, increase of inflammatory cytokines and host risk factors. This study aims to explore the significance of cervical immune mediators associated to cell survival, angiogenesis and interaction with immune response, in predicting the risk to develop HPV-related intraepithelial lesions. Methods A panel of 48 cytokines and growth factors were explored in a selected cohort of 168 immunocompetent women including 88 diagnosed with low (LSIL) or high (HSIL) squamous intraepithelial lesions of the cervix and 80 with normal cervical cytology (NIL). HPV genotyping was performed by Linear Array HPV test and the soluble concentration of 48 immune molecules was analyzed using the Bio-Plex platform. Results The prevalence of single HR-HPV infection was 30% in NIL and 100% in LSIL and HSIL women. The expression of 13 cytokines, including interleukins IL-6, IL-3, IL-12p40, IL-12p70, IL-16, IL-18, LIF, of chemokines CCL7 (MCP-3), CXCL9 (MIG), CXCL12 (SDF-1α) and of the tropic factors VEGF, G-CSF, M-CSF were significantly associated with the presence of infection, with levels being higher in women with precancerous lesions compared to NIL HPV negative women. Only the growth factor GM-CSF was positively associated with the cytological abnormalities. Conclusions The ability of HR-HPV to escape from innate immune recognition and to orchestrate the production of specific inflammatory and growth factors, involved in early inflammatory response and in the cell-proliferating phase of intraepithelial damage, was documented in women before the development of cervical lesions. PMID:26990868

  14. Screening and detection of human papillomavirus (HPV) high-risk strains HPV16 and HPV18 in saliva samples from subjects under 18 years old in Nevada: a pilot study.

    PubMed

    Flake, Colton; Arafa, Jamal; Hall, Alex; Ence, Eryn; Howard, Katherine; Kingsley, Karl

    2012-10-22

    Human papillomaviruses (HPV) are oncogenic and mainly associated with cervical cancers. Recent evidence has demonstrated HPV infection in other tissues, including oral epithelia and mucosa. Although a recent pilot study provided new information about oral HPV status in healthy adults from Nevada, no information was obtained about oral HPV prevalence among children or teenagers, therefore, the goal of this study is to provide more detailed information about oral prevalence of high-risk HPV among children and teenagers in Nevada. This retrospective study utilized previously collected saliva samples, obtained from pediatric dental clinic patients (aged 2 - 11) and local school district teenagers (aged 12-17) for high-risk HPV screening (n=118) using qPCR for quantification and confirmation of analytical sensitivity and specificity. A small subset of saliva samples were found to harbor high-risk HPV16 (n=2) and HPV18 (n=1), representing a 2.5% of the total. All three were obtained from teenage males, and two of these three samples were from White participants. Although this retrospective study could not provide correlations with behavioral or socioeconomic data, this project successfully screened more than one hundred saliva samples for high-risk HPV, confirming both HPV16 and HPV18 strains were present in a small subset. With increasing evidence of oral HPV infection in children, this study provides critical information of significant value to other dental, medical, oral and public health professionals who seek to further an understanding of oral health and disease risk in pediatric populations.

  15. Screening and detection of human papillomavirus (HPV) high-risk strains HPV16 and HPV18 in saliva samples from subjects under 18 years old in Nevada: a pilot study

    PubMed Central

    2012-01-01

    Background Human papillomaviruses (HPV) are oncogenic and mainly associated with cervical cancers. Recent evidence has demonstrated HPV infection in other tissues, including oral epithelia and mucosa. Although a recent pilot study provided new information about oral HPV status in healthy adults from Nevada, no information was obtained about oral HPV prevalence among children or teenagers, therefore, the goal of this study is to provide more detailed information about oral prevalence of high-risk HPV among children and teenagers in Nevada. Methods This retrospective study utilized previously collected saliva samples, obtained from pediatric dental clinic patients (aged 2 – 11) and local school district teenagers (aged 12-17) for high-risk HPV screening (n=118) using qPCR for quantification and confirmation of analytical sensitivity and specificity. Results A small subset of saliva samples were found to harbor high-risk HPV16 (n=2) and HPV18 (n=1), representing a 2.5% of the total. All three were obtained from teenage males, and two of these three samples were from White participants. Conclusions Although this retrospective study could not provide correlations with behavioral or socioeconomic data, this project successfully screened more than one hundred saliva samples for high-risk HPV, confirming both HPV16 and HPV18 strains were present in a small subset. With increasing evidence of oral HPV infection in children, this study provides critical information of significant value to other dental, medical, oral and public health professionals who seek to further an understanding of oral health and disease risk in pediatric populations. PMID:23088565

  16. Up-regulation of lipocalin 2 is associated with high-risk human papillomavirus and grade of cervical lesion at baseline but does not predict outcomes of infections or incident cervical intraepithelial neoplasia.

    PubMed

    Syrjänen, Stina; Naud, Paulo; Sarian, Luis; Derchain, Sophie; Roteli-Martins, Cecilia; Tatti, Silvio; Branca, Margerita; Erzen, Mojca; Hammes, Luciano S; Costa, Silvano; Longatto-Filho, Adhemar; Syrjänen, Kari

    2010-07-01

    Our objective was to assess whether neutrophil gelatinase-associated lipocalin (NGAL)/lipocalin 2 (LCN2) expression in cervical human papillomavirus (HPV) lesions has implications on the outcome of HPV infections or disease progression. Cervical biopsy specimens from 225 women in the Latin American Screening study were analyzed for NGAL/LCN2 expression using immunohistochemical analysis, to assess associations with cervical intraepithelial neoplasia (CIN) grade, high-risk HPV, and in predicting outcomes of high-risk (HR)-HPV infections. Expression of NGAL/LCN2 increased with lesion grade (odds ratio [OR], 3.86; 95% confidence interval [CI], 1.53-9.71; P = .001). Up-regulation was also related to HR-HPV detection (OR, 2.21; 95% CI, 1.15-4.24; P = .016) and showed a linear relationship to HR-HPV load (P = .002). NGAL/LCN2 expression was of no value in predicting the outcomes of HR-HPV infections or the surrogate end points (incident CIN 1+ and CIN 2+) of progressive disease. Because the SV40 large T antigen is a powerful up-regulator of this lipocalin, up-regulation of NGAL/LCN2 in CIN is probably induced by HR-HPV E6 oncoprotein, most likely by eliminating its normal transcription repression exerted by wild-type p53.

  17. Comparison of the Roche Cobas(®) 4800 HPV assay to Digene Hybrid Capture 2, Roche Linear Array and Roche Amplicor for Detection of High-Risk Human Papillomavirus Genotypes in Women undergoing treatment for cervical dysplasia.

    PubMed

    Phillips, Samuel; Garland, Suzanne M; Tan, Jeffery H; Quinn, Michael A; Tabrizi, Sepehr N

    2015-01-01

    The recently FDA (U.S. food and drug administration) approved Roche Cobas(®) 4800 (Cobas) human papillomavirus (HPV) has limited performance data compared to current HPV detection methods for test of cure in women undergoing treatment for high grade lesions. Evaluation of Cobas HPV assay using historical samples from women undergoing treatment for cervical dysplasia. A selection of 407 samples was tested on the Cobas assay and compared to previous results from Hybrid Capture 2, HPV Amplicor and Roche Linear Array. Overall, a correlation between high-risk HPV positivity and high grade histological diagnosis was 90.6% by the Cobas, 86.1% by Hybrid Capture 2, 92.9% by HPV Amplicor and 91.8% by Roche Linear Array. The Cobas HPV assay is comparative to both the HPV Amplicor and Roche Linear Array assays and better than Hybrid capture 2 assay in the detection of High-Risk HPV in women undergoing treatment for cervical dysplasia. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. A cross-sectional study of high-risk human papillomavirus clustering and cervical outcomes in HIV-infected women in Rio de Janeiro, Brazil.

    PubMed

    Castilho, Jessica L; Levi, José Eduardo; Luz, Paula M; Cambou, Mary Catherine; Vanni, Tazio; de Andrade, Angela; Derrico, Mônica; Veloso, Valdiléa G; Grinsztejn, Beatriz; Friedman, Ruth K

    2015-06-23

    In Brazil, the rate of cervical cancer remains high despite the availability of screening programs. With ongoing vaccine development and implementation, information on the prevalence of specific HPV types is needed, particularly among high-risk populations, such as HIV-infected women. We performed a study of HIV-infected women in Rio de Janeiro, Brazil, who underwent cervical HPV genotype testing between 2005-2013. We examined the prevalence of high-risk HPV types and the patterns of high-risk HPV type clustering. Using logarithmic binomial regression, we estimated the risk of abnormal cytology by HPV genotype result. Of the 562 women included, 498 (89 %) had at least one HPV type detected. 364 women (65 %) had at least one high-risk HPV type detected and 181 (32 %) had more than one high-risk type detected. HPV 58 was the most frequent HPV type detected overall (prevalence 19.8 % [95 % confidence interval 16.4-23.1]), followed by HPV 53 (prevalence 15.5 % [12.5-18.5]) and HPV 16 (prevalence 13 % [10.2-15.8]). Women infected with more than one high-risk HPV type were younger, had lower CD4+ lymphocyte counts, and were more likely to be infected with HPV 16 or 18. In adjusted analyses, presence of more than one high-risk HPV type was associated with a two-fold increased risk of abnormal cytology after adjusting for presence of individual high-risk type, age, and CD4+ lymphocyte count (adjusted prevalence ratios 1.88-2.07, all p <0.001). No single high-risk HPV type was statistically associated with abnormal cytology after adjusting for the presence of more than one high-risk HPV type. In the largest study of cervical HPV genotypes among HIV-infected women in Latin America, infection by high-risk HPV types other than 16 or 18 and infection by more than one high-risk HPV types were common. Infection by more than one high-risk type was more strongly associated with abnormal cervical cytology than any individual high-risk HPV type, highlighting the need for multi

  19. 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.

  20. Human Papillomavirus - Prevalence of High-Risk and Low-Risk Types among Females Aged 14-59 Years, National Health and ...

    MedlinePlus

    ... High-risk and Low-risk Types Among Females Aged 14 – 59 Years, National Health and Nutrition Examination ... Racial and Ethnic Minorities Figures Men Who Have Sex with Men Figures Tables Appendix Interpreting STD Surveillance ...

  1. p16-positive lymph node metastases from cutaneous head and neck squamous cell carcinoma: No association with high-risk human papillomavirus or prognosis and implications for the workup of the unknown primary.

    PubMed

    McDowell, Lachlan J; Young, Richard J; Johnston, Meredith L; Tan, Tze-Jian; Kleid, Stephen; Liu, Chen S; Bressel, Mathias; Estall, Vanessa; Rischin, Danny; Solomon, Benjamin; Corry, June

    2016-04-15

    The incidence of p16 overexpression and the role of human papillomavirus (HPV) in cutaneous head and neck squamous cell carcinoma (cHNSCC) are unclear. One hundred forty-three patients with cHNSCC lymph node metastases involving the parotid gland were evaluated for p16 expression by immunohistochemistry. The detection of 18 high-risk HPV subtypes was performed with HPV RNA in situ hybridization for a subset of 59 patients. The results were correlated with clinicopathological features and outcomes. The median follow-up time was 5.3 years. No differences were observed in clinicopathological factors with respect to the p16 status. p16 was positive, weak, and negative in 45 (31%), 21 (15%), and 77 cases (54%), respectively. No high-risk HPV subtypes were identified, regardless of the p16 status. The p16 status was not prognostic for overall (hazard ratio, 1.08; 95% confidence interval [CI], 0.85-1.36; P = .528), cancer-specific (hazard ratio, 1.12; 95% CI, 0.77-1.64; P = .542), or progression-free survival (hazard ratio, 1.03; 95% CI, 0.83-1.29; P = .783). Distant metastasis-free survival, freedom from locoregional failure, and freedom from local failure were also not significantly associated with the p16 status. p16 positivity is common but not prognostic in cHNSCC lymph node metastases. High-risk HPV subtypes are not associated with p16 positivity and do not appear to play a role in this disease. HPV testing, in addition to the p16 status in the unknown primary setting, may provide additional information for determining a putative primary site. © 2016 American Cancer Society.

  2. Awareness and knowledge of Human Papillomavirus (HPV) infection among high-risk men of Hispanic origin attending a Sexually Transmitted Infection (STI) clinic

    PubMed Central

    2012-01-01

    Background Genital Human papilloma virus (HPV) is one of the most commonly diagnosed Sexually Transmitted Infection (STIs) in men and women. Knowledge about HPV infection among men is limited. This study aims to determine correlates of adequate knowledge of HPV infection among men who attend an STI clinic in Puerto Rico. Methods A cross-sectional study of 206 men was conducted at an STI clinic in San Juan, PR. Adequate knowledge was defined as a score of at least 70% of correct responses among those men who reported having ever heard of HPV. Variables that achieved statistical significance in the bivariate analysis (p<0.05) were included in the multivariate logistic regression model. Results Although 52.5% of men reported having heard of HPV infection before the survey, only 29.3% of this sub-group had an adequate knowledge of HPV. Most men did not know that HPV is a risk factor for anal (38.7%), penile (50.0%) and oral (72.6%) cancer. Factors associated with adequate knowledge of HPV in age-adjusted models were being men who have sex with men (MSM) (OR=2.6;95%CI=1.1-6.1), self-report of genital warts (OR=3.2;95%CI=1.3-7.9) and herpes (OR=7.4;95% CI=2.2-25.1). MSM was marginally associated with adequate knowledge (OR=2.3;95% CI=0.9-5.9) and self-report of herpes remained significantly associated (OR=5.0;95%CI=1.3-18.4) in multivariate logistic regression analysis. Conclusions Awareness and knowledge of HPV was very low in this group of men. Interventions to increase knowledge and awareness in this group are necessary to promote preventive practices for HPV-related cancers in high-risk groups. PMID:23231727

  3. Human papillomaviruses in epigenetic regulations.

    PubMed

    Durzynska, Julia; Lesniewicz, Krzysztof; Poreba, Elzbieta

    Human Papillomaviruses (HPVs) are double-stranded DNA viruses, that infect epithelial cells and are etiologically involved in the development of human cancer. Today, over 200 types of human papillomaviruses are known. They are divided into low-risk and high-risk HPVs depending on their potential to induce carcinogenesis, driven by two major viral oncoproteins, E6 and E7. By interacting with cellular partners, these proteins are involved in interdependent viral and cell cycles in stratified differentiating epithelium, and concomitantly induce epigenetic changes in infected cells and those undergoing malignant transformation. E6 and E7 oncoproteins interact with and/or modulate expression of many proteins involved in epigenetic regulation, including DNA methyltransferases, histone-modifying enzymes and subunits of chromatin remodeling complexes, thereby influencing host cell transcription program. Furthermore, HPV oncoproteins modulate expression of cellular micro RNAs. Most of these epigenetic actions in a complex dynamic interplay participate in the maintenance of persistent infection, cell transformation, and development of invasive cancer by a considerable deregulation of tumor suppressor and oncogenes. In this study, we have undertaken to discuss a number of studies concerning epigenetic regulations in HPV-dependent cells and to focus on those that have biological relevance to cancer progression. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  4. A conserved C-terminal sequence of high-risk cutaneous beta-human papillomavirus E6 proteins alters localization and signalling of β1-integrin to promote cell migration.

    PubMed

    Holloway, Amy; Storey, Alan

    2014-01-01

    Beta-human papillomaviruses (β-HPV) infect cutaneous epithelia, and accumulating evidence suggests that the virus may act as a co-factor with UV-induced DNA damage in the development and progression of non-melanoma skin cancer, although the molecular mechanisms involved are poorly understood. The E6 protein of cutaneous β-HPV types encodes functions consistent with a role in tumorigenesis, and E6 expression can result in papilloma formation in transgenic animals. The E6 proteins of high-risk α-HPV types, which are associated with the development of anogenital cancers, have a conserved 4 aa motif at their extreme C terminus that binds to specific PDZ domain-containing proteins to promote cell invasion. Likewise, the high-risk β-HPVs HPV5 and HPV8 E6 proteins also share a conserved C-terminal motif, but this is markedly different from that of α-HPV types, implying functional differences. Using binding and functional studies, we have shown that β-HPV E6 proteins target β1-integrin using this C-terminal motif. E6 expression reduced membrane localization of β1-integrin, but increased overall levels of β1-integrin protein and its downstream effector focal adhesion kinase in human keratinocytes. Altered β1-integrin localization due to E6 expression was associated with actin cytoskeleton rearrangement and increased cell migration that was abolished by point mutations in the C-terminal motif of E6. We concluded that modulation of β1-integrin signalling by E6 proteins may contribute towards the pathogenicity of these β-HPV types.

  5. Evaluation of p16/Ki-67 dual-stained cytology as triage test for high-risk human papillomavirus-positive women.

    PubMed

    Ebisch, Renée Mf; van der Horst, Judith; Hermsen, Meyke; Rijstenberg, L Lucia; Vedder, Judith Em; Bulten, Johan; Bosgraaf, Remko P; Verhoef, Viola Mj; Heideman, Daniëlle Am; Snijders, Peter Jf; Meijer, Chris Jlm; van Kemenade, Folkert J; Massuger, Leon Fag; Melchers, Willem Jg; Bekkers, Ruud Lm; Siebers, Albert G

    2017-03-17

    The aim of this study was to evaluate the clinical utility of p16/Ki-67 dual staining, for the identification of CIN in high-risk HPV-positive women from a non-responder screening cohort. P16/Ki-67 dual staining, Pap cytology, and HPV16/18 genotyping were performed on physician-taken liquid-based samples from 495 women who tested high-risk HPV positive on self-sampled material (PROHTECT-3B study). Different triage strategies involving p16/Ki-67 dual staining were evaluated for sensitivity, specificity, and predictive value for ≥CIN2 and ≥CIN3, and compared to Pap cytology with a threshold of atypical cells of undetermined significance. Centrally revised histology or an adjusted endpoint with combined high-risk HPV negative and cytology negative follow-up at 6 months was used as gold standard. Pap cytology (threshold atypical cells of undetermined significance) triage of high-risk HPV-positive samples showed a sensitivity of 93% (95% confidence interval: 85-98) with a specificity of 49% (95% confidence interval: 41-56) for ≥CIN3. Three triage strategies with p16/Ki-67 showed a significantly increased specificity with similar sensitivity. P16/Ki-67 triage of all high-risk HPV-positive samples had a sensitivity of 92% (95% confidence interval: 84-97) and a specificity of 61% (95% confidence interval: 54-69) for ≥CIN3. Applying p16/Ki-67 triage to only high-risk HPV-positive women with low-grade Pap cytology showed a similar sensitivity of 92% (95% confidence interval: 84-97), with a specificity for ≥CIN3 of 64% (95% confidence interval: 56-71). For high-risk HPV-positive women with low-grade and normal Pap cytology, triage with p16/Ki-67 showed a sensitivity of 96% (95% confidence interval: 89-99), and a specificity of 58% (95% confidence interval: 50-65). HPV16/18 genotyping combined with Pap cytology showed a sensitivity and specificity for ≥CIN3 similar to Pap cytology with an atypical cells of undetermined significance threshold. Because the quality of

  6. Oncogenic human papillomaviruses.

    PubMed

    McBride, Alison A

    2017-10-19

    Human papillomaviruses (HPVs) are an ancient group of viruses with small, double-stranded DNA circular genomes. They are species-specific and have a strict tropism for mucosal and cutaneous stratified squamous epithelial surfaces of the host. A subset of these viruses has been demonstrated to be the causative agent of several human cancers. Here, we review the biology, natural history, evolution and cancer association of the oncogenic HPVs.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Authors.

  7. Oncogenic human papillomaviruses

    PubMed Central

    2017-01-01

    Human papillomaviruses (HPVs) are an ancient group of viruses with small, double-stranded DNA circular genomes. They are species-specific and have a strict tropism for mucosal and cutaneous stratified squamous epithelial surfaces of the host. A subset of these viruses has been demonstrated to be the causative agent of several human cancers. Here, we review the biology, natural history, evolution and cancer association of the oncogenic HPVs. This article is part of the themed issue ‘Human oncogenic viruses’. PMID:28893940

  8. Human Papillomavirus and Cervical Cancer

    PubMed Central

    Burd, Eileen M.

    2003-01-01

    Of the many types of human papillomavirus (HPV), more than 30 infect the genital tract. The association between certain oncogenic (high-risk) strains of HPV and cervical cancer is well established. Although HPV is essential to the transformation of cervical epithelial cells, it is not sufficient, and a variety of cofactors and molecular events influence whether cervical cancer will develop. Early detection and treatment of precancerous lesions can prevent progression to cervical cancer. Identification of precancerous lesions has been primarily by cytologic screening of cervical cells. Cellular abnormalities, however, may be missed or may not be sufficiently distinct, and a portion of patients with borderline or mildly dyskaryotic cytomorphology will have higher-grade disease identified by subsequent colposcopy and biopsy. Sensitive and specific molecular techniques that detect HPV DNA and distinguish high-risk HPV types from low-risk HPV types have been introduced as an adjunct to cytology. Earlier detection of high-risk HPV types may improve triage, treatment, and follow-up in infected patients. Currently, the clearest role for HPV DNA testing is to improve diagnostic accuracy and limit unnecessary colposcopy in patients with borderline or mildly abnormal cytologic test results. PMID:12525422

  9. [Network Research on Human Papillomavirus].

    PubMed

    Almeida-Gutiérrez, Eduardo; Paniagua, Ramón; Furuya, María ElenaYuriko

    2015-01-01

    In order to increase the research in important health questions at a national and institutional levels, the Human Papillomavirus Research Network of the Health Research Coordination of the Instituto Mexicano del Seguro Social offers this supplement with the purpose of assisting patients that daily look for attention due to the human papillomavirus or to cervical cancer.

  10. Significant association of high-risk human papillomavirus (HPV) but not of p53 polymorphisms with oral squamous cell carcinomas in Malaysia.

    PubMed

    Saini, Rajan; Tang, Thean-Hock; Zain, Rosnah Binti; Cheong, Sok Ching; Musa, Kamarul Imran; Saini, Deepti; Ismail, Abdul Rashid; Abraham, Mannil Thomas; Mustafa, Wan Mahadzir Wan; Santhanam, Jacinta

    2011-02-01

    The purpose of this study was to evaluate the role of HPV and p53 polymorphisms in oral squamous cell carcinomas (OSCC) affecting Malaysian population. We analysed frozen samples from 105 OSCC as well as 105 oral specimens derived from healthy individuals. PCR assays targeting two regions of the virus were used. PCR amplification for the analysis of p53 codon 72 arginine/proline alleles was carried out in a separate reaction. HPV DNA was detected in 51.4% OSCC samples, while 24.8% controls were found to be HPV positive. HPV was found to be significantly associated with OSCC (P < 0.001, OR = 4.3 after adjustment for habits) when compared to controls. High-risk HPV was found to be significantly associated with OSCC cases (P < 0.05). Demographic profiles of age, gender, race and habits were not associated with HPV presence in cases and controls. However, significantly less HPV positivity was seen in poorly differentiated compared to well-differentiated OSCCs. No significant association was found between HPV positivity and p53 polymorphisms in cases and control groups. Additionally, we found no association of codon 72 polymorphism with oral cancer. This study indicates that high-risk HPV infection is one of the contributing factors for OSCCs. HPV 16 was the predominant type found in Malaysian patients with OSCC. Further, we did not find any association between p53 codon 72 polymorphism and HPV infection or between the p53 polymorphism and the risk of oral cancer.

  11. Detection Rate of High-Grade Cervical Neoplasia and Cost-Effectiveness of High-Risk Human Papillomavirus Genotyping with Reflex Liquid-based Cytology in Cervical Cancer Screening.

    PubMed

    Tay, Sun Kuie; Lin, Lynette Eo; Goh, Ronald Ch

    2017-07-01

    This study aimed to determine the prevalence of cervical intraepithelial neoplasia grade 3 or worse (≥CIN3) and cost-effectiveness of human papillomavirus (HPV) genotyping with reflex liquid-based cytology (LBC) for cervical cancer screening in Singapore. Women who were ≥25 years old and undertook co-testing with LBC and HPV-genotyping (Cobas-4800, Roche, USA) for HPV-16, HPV-18 and 12 high-risk HPV types in a single institution were studied retrospectively. A single cervical smear in ThinPrep® PreservCyt® solution (Hologic, USA) was separated for tests in independent cytology and molecular pathology laboratories. The results were reviewed by a designated gynaecologist according to institutional clinical management protocols. Those who tested positive for HPV-16 and/or HPV-18 (regardless of cytology results), cytology showing low-grade squamous intraepithelial lesions (LSIL) or high-grade SIL (HSIL), or atypical squamous cells of undetermined significance (ASCUS) with positive 12 high-risk HPV types were referred for colposcopy. Colposcopy was performed by experienced colposcopists. Cervical biopsy, either directed punch biopsies or excisional biopsy, was determined by a colposcopist. The diagnosis of ≥CIN3 was reviewed by a gynaecologic pathologist. Cost-effectiveness of HPV-based screening in terms of disease and financial burden was analysed using epidemiological, clinical and financial input data from Singapore. Of 1866 women studied, 167 (8.9%) had abnormal cytology (≥ASCUS) and 171 (9.2%) tested positive for high-risk HPV. Twenty-three CIN were detected. Three of the 10 ≥CIN3 cases had negative cytology but positive HPV-16. Compared to cytology, HPV genotyping detected more ≥CIN3 (OR: 1.43). HPV+16/18 genotyping with reflex LBC was superior in terms of cost-effectiveness to LBC with reflex HPV, both for disease detection rate and cost per case of ≥CIN2 detected. Compared to cytology, HPV+16/18 genotyping with reflex LBC detected more ≥CIN3

  12. Implication of high risk human papillomavirus HR-HPV infection in prostate cancer in Indian population--a pioneering case-control analysis.

    PubMed

    Singh, Neha; Hussain, Showket; Kakkar, Nandita; Singh, Shrawan K; Sobti, Ranbir C; Bharadwaj, Mausumi

    2015-01-16

    Prostate cancer is the second most common cancer with sexual history as a consistent risk factor. This is the pioneering study that evaluates the frequency of HPV infection in prostate cancer in India. Ninety five (95) histopathologically confirmed cancer and fifty five (55) BPH from Indian population were analyzed for HPV infection using a pair of consensus sequence primer followed by type specific PCRs for both high-risk and low-risk HPV types. The data demonstrate HPV infection in 41% of prostate tumor biopsies and 20% in BPH. Subsequent PCR- based HPV typing using type - specific primers revealed 32% were infected with HPV type 16 whereas 6% were found to be positive for HPV type 18, while in BPH controls only 5% of the BPH controls were infected with HPV 16 and this difference was highly significant (p = 0.0004). Significant proportion of HPV infected (74%) cases belonged to stage III and IV (p < 0.001) with a high Gleason score ≥ 8 (p = 0.003). The study represents for the first time the incidence of HPV infection in prostate cancer in Indian population and strengthens the hypothesis that HPV infection could be one of the co factor associated with progression of prostate cancer.

  13. Post-Loop Electrosurgical Excision Procedure High-Risk Human Papillomavirus Testing as a Test of Cure: The British Columbia Experience.

    PubMed

    Ceballos, Kathy M; Lee, Marette; Cook, Darrel A; Smith, Laurie W; Gondara, Lovedeep; Krajden, Mel; van Niekerk, Dirk J; Coldman, Andrew J

    2017-10-01

    To determine whether Hybrid Capture 2 High-Risk HPV DNA Test (HC2) can be used as a test of cure in women treated for cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) and allow discharge from colposcopy follow-up with a return to a cytology-based screening program for HC2-negative women. Data were analyzed for all women who underwent a loop electrosurgical excision procedure between August 1, 2008, and June 30, 2011, and had a valid HC2 result after loop electrosurgical excision procedure and follow-up histopathology result, to determine risk of persistent or recurrent CIN 2+ in HC2-positive and HC2-negative women. Two thousand three hundred forty women had adequate biopsies and valid HC2 results. Of 460 HC2-positive women, 118 (25.7%) were diagnosed with CIN 2+, whereas of 1,880 HC2-negative women, 35 (1.9%) had a subsequent diagnosis of CIN 2+ (p < .0002) yielding a HC2-negative predictive value of 98.1% (95% confidence interval = 97.4-98.7). Of 460 HC2-positive women, 306 initially had negative biopsies. In the subsequent 36 months, 38 of the 306 were diagnosed with CIN 2+. We conclude that women with a negative HC2 test can safely return to routine annual cytology screening by primary care providers while women who test HC2 positive are at higher risk and should continue to be followed by colposcopy, even if their initial biopsy is negative.

  14. Human papillomavirus in oral lesions.

    PubMed

    González, Joaquín V; Gutiérrez, Rafael A; Keszler, Alicia; Colacino, Maria del Carmen; Alonio, Lidia V; Teyssie, Angelica R; Picconi, Maria Alejandra

    2007-01-01

    Growing evidence suggests a role for human papillomavirus (HPV) in oral cancer; however its involvement is still controversial. This study evaluates the frequency of HPV DNA in a variety of oral lesions in patients from Argentina. A total of 77 oral tissue samples from 66 patients were selected (cases); the clinical-histopathological diagnoses corresponded to: 11 HPV- associated benign lesions, 8 non-HPV associated benign lesions, 33 premalignant lesions and 25 cancers. Sixty exfoliated cell samples from normal oral mucosa were used as controls. HPV detection and typing were performed by polymerase chain reaction (PCR) using primers MY09, 11, combined with RFLP or alternatively PCR using primers GP5+, 6+ combined with dot blot hybridization. HPV was detected in 91.0% of HPV- associated benign lesions, 14.3% of non-HPV associated benign lesions, 51.5% of preneoplasias and 60.0% of cancers. No control sample tested HPV positive. In benign HPV- associated lesions, 30.0% of HPV positive samples harbored high-risk types, while in preneoplastic lesions the value rose to 59.9%. In cancer lesions, HPV detection in verrucous carcinoma was 88.9% and in squamous cell carcinoma 43.8%, with high-risk type rates of 75.5% and 85.6%, respectively. The high HPV frequency detected in preneoplastic and neoplastic lesions supports an HPV etiological role in at least a subset of oral cancers.

  15. Application of a multiplex PCR to cervical cells collected by a paper smear for the simultaneous detection of all mucosal human papillomaviruses (HPVs) and typing of high-risk HPV types 16 and 18.

    PubMed

    Shukla, Shirish; Bharti, Alok C; Mahata, Sutapa; Hussain, Showket; Hedau, Suresh; Sharma, Rajyashri; Pillai, M Radhakrishna; Krishna, Sudhir; Chiplunkar, Shubhada; Tongaonkar, Hemant; Das, Bhudev C

    2010-11-01

    A simple paper smear (PS) method for dry collection and storage of cervical specimens was employed to develop an easy multiplex (MPX) PCR for simultaneous detection of generic human papillomaviruses (HPVs) as well as typing of the high-risk HPV-16 and -18, the two clinically most important HPV genotypes, which are responsible for more than 80 % of cervical cancers. Multiplexing was performed with a small amount of DNA eluted by boiling from a single PS punch in a single tube and using a mixture of four pairs of primers specific for the HPV L1 consensus sequence, HPV-16, HPV-18 and the β-globin gene. Sixty HPV-positive biopsies and corresponding PS specimens from cervical cancer patients as well as cervical smears from 100 healthy women with or without abnormal cytology were collected both as PSs and in PBS. Detection of HPV DNA from cervical biopsies collected in PBS and corresponding cervical scrapes on a PS or in PBS by conventional and MPX-PCR showed a concordance of 100 % and adequacy of 93 %. A similar comparative study in cervical scrapes from normal women also revealed 100 % concordance. The technique was validated in a multicentric study at four different national laboratories. PSs collected by different centres showed variable adequacy (73-82 %) but the use of multiple PS discs for DNA extraction significantly increased the adequacy. Integration of PSs with MPX-PCR for the detection and typing of HPVs is a highly convenient, efficient, simple and cost-effective method for large-scale clinico-epidemiological studies and is also suitable for HPV vaccine monitoring programmes in resource-poor settings.

  16. Comparison of the Abbott RealTime High-Risk Human Papillomavirus (HPV), Roche Cobas HPV, and Hybrid Capture 2 assays to direct sequencing and genotyping of HPV DNA.

    PubMed

    Park, Yongjung; Lee, Eunhee; Choi, Jonghyeon; Jeong, Seri; Kim, Hyon-Suk

    2012-07-01

    Infection with high-risk (HR) human papillomavirus (HPV) genotypes is an important risk factor for cervical cancers. We evaluated the clinical performances of two new real-time PCR assays for detecting HR HPVs compared to that of the Hybrid Capture 2 test (HC2). A total of 356 cervical swab specimens, which had been examined for cervical cytology, were assayed by Abbott RealTime HR and Roche Cobas HPV as well as HC2. Sensitivities and specificities of these assays were determined based on the criteria that concordant results among the three assays were regarded as true-positive or -negative and that the results of genotyping and sequencing were considered true findings when the HPV assays presented discrepant results. The overall concordance rate among the results for the three assays was 82.6%, and RealTime HR and Cobas HPV assays agreed with HC2 in 86.1% and 89.9% of cases, respectively. The two real-time PCR assays agreed with each other for 89.6% of the samples, and the concordance rate between them was equal to or greater than 98.0% for detecting HPV type 16 or 18. HC2 demonstrated a sensitivity of 96.6% with a specificity of 89.1% for detecting HR HPVs, while RealTime HR presented a sensitivity of 78.3% with a specificity of 99.2%. The sensitivity and specificity of Cobas HPV for detecting HR HPVs were 91.7% and 97.0%. The new real-time PCR assays exhibited lower sensitivities for detecting HR HPVs than that of HC2. Nevertheless, the newly introduced assays have an advantage of simultaneously identifying HPV types 16 and 18 from clinical samples.

  17. Prevalence, distribution, and viral burden of all 15 high-risk human papillomavirus types in adenosquamous carcinoma of the uterine cervix: a multiplex real-time polymerase chain reaction-based study.

    PubMed

    Quddus, M Ruhul; Manna, Pradip; Sung, C James; Kerley, Spencer; Steinhoff, Margaret M; Lawrence, W Dwayne

    2014-02-01

    Human papillomavirus (HPV) 16 and 18 are the types most commonly found in cervical adenosquamous carcinoma. Multiple HPV types have been found in cervical adenocarcinoma but not in the adenosquamous variant. Type-specific detection of high-risk (HR) HPV allows the detection of co-infection by multiple HPV types and assessment of viral load per cell. Our aim was to identify and quantify all HR HPV types in cervical adenosquamous carcinoma and to correlate viral loads with prognosis-related histologic features. All 15 HR HPV types were tested for by multiplex real-time polymerase chain reaction, and standard curves were created for each type. Viral loads were determined retrospectively. Prognosis-related histologic features were correlated with specific HPV types and the viral loads. A total of 80% of the tumors examined expressed HPV. Types 16/18 were detected in 86% of these cases, whereas the remaining 14% of the positive cases were infected by other types. A single type of virus was detected in 67% of cases, 2 in 29%, and 3 in 4%. Poor prognostic features were seen in 84.6% of the tumors infected with HPV 16, 46% of those infected with HPV 18, and 100% of those infected with other types. As expected, HPV 16, HPV 18, or both were the most frequent viral types; HPV 73 was the next most frequent type. Multiple HPV types were detected in 33% of the tumors. Non-HPV 16/18 cases had low viral loads, but all of these had poor prognosis-related histologic features. Two of the three recurrent cases had multiple viral types. © 2014 Elsevier Inc. All rights reserved.

  18. Immunosuppressive cytokine Interleukin-10 (IL-10) is up-regulated in high-grade CIN but not associated with high-risk human papillomavirus (HPV) at baseline, outcomes of HR-HPV infections or incident CIN in the LAMS cohort.

    PubMed

    Syrjänen, Stina; Naud, Paulo; Sarian, Luis; Derchain, Sophie; Roteli-Martins, Cecilia; Longatto-Filho, Adhemar; Tatti, Silvio; Branca, Margherita; Erzen, Mojca; Hammes, L S; Costa, S; Syrjänen, Kari

    2009-12-01

    Bypassing the local immunological defense reactions in the cervix is one of the prerequisites for human papillomaviruses (HPV) infections to progress to intraepithelial neoplasia (CIN). The role of potent immunosuppressive cytokines, e.g., interleukin-10 (IL-10), depressing these local virus-specific immunological responses is incompletely studied. To assess, whether IL-10 expression in cervical HPV lesions has any implications in the outcome of HPV infections or disease progression to CIN. Baseline cervical biopsies from 225 women of the LAMS study sub-cohort were analyzed for IL-10 expression using immunohistochemistry, to assess its associations with CIN grade, and high-risk HPV (HR-HPV) at baseline, as well as in predicting outcomes of HR-HPV infections, and development of incident CIN1+ and CIN2+ in this longitudinal setting. Expression of IL-10 in cervical lesions was up-regulated most often in high-grade CIN, and IL-10 over-expression retained its value as independent predictor of CIN2+ (odds ratio (OR) = 4.92) and CIN3+ (OR = 7.51) also in multivariate model, including HR-HPV and several known covariates of IL-10 expression. Up-regulation was not related to HR-HPV detection, and showed no relationship to HR-HPV viral loads. Using longitudinal predictive indicators (SE, SP, PPV, NPV), IL-10 expression was of no value in predicting (1) the outcomes of HR-HPV infections, or (2) the surrogate endpoints (incident CIN1+, CIN2+) of progressive disease. IL-10 over-expression (along with HR-HPV) was one of the independent covariates of CIN2/3. This immunosuppressive cytokine might play an important role in creating a microenvironment that favors progressive cervical disease and immune evasion by HR-HPV.

  19. p300 expression is related to high-risk human papillomavirus infections and severity of cervical intraepithelial neoplasia but not to viral or disease outcomes in a longitudinal setting.

    PubMed

    Syrjänen, Stina; Naud, Paulo; Sarian, Luis; Derchain, Sophie; Roteli-Martins, Cecilia; Longatto-Filho, Adhemar; Tatti, Silvio; Branca, Margherita; Erzen, Mojca; Serpa-Hammes, Luciano; Matos, Jean; Arlindo, Fernanda; Sakamoto-Maeda, Marina; Costa, Silvano; Syrjänen, Kari

    2010-03-01

    To evaluate the role of the expression of the transcription factor p300 as an independent predictor of high-risk human papillomavirus (HR-HPV) infections and outcome of the cervical disease.Cervical biopsy samples taken at enrolment from 225 women of the Latin American Screening study cohort were analyzed for p300 using immunohistochemistry to assess its value as predictor of (a) cervical intraepithelial neoplasia (CIN) grade, and (b) HR-HPV at baseline, as well as (c) outcomes of HR-HPV infections, and (d) development of incident CIN as surrogate endpoints of progressive disease.There was a significant linear trend in increasing upregulation (=pattern shift) of p300 (P=0.0001) in parallel with increasing grade of CIN. When dichotomized (normal/moderately increase vs. strong-intense), upregulated p300 expression predicted CIN3+ with odds ratio=4.16 (95% confidence interval: 1.95-8.86) (P=0.0001) and CIN2+ with odds ratio=3.48 (95% confidence interval: 1.86-6.48) (P=0.0001). p300 was upregulated more often in HR-HPV+ lesions than in those remaining negative. Semiquantitative viral loads were also directly related to upregulation of p300 (P=0.036), but p300 was not a significant predictor of disease progression to either CIN1+ or CIN2+.p300 expression was upregulated in CIN lesions and related to detection and viral load of HR-HPV but not to their outcome or to incident CIN.

  20. The role of high-risk human papillomavirus infection in oral and oropharyngeal squamous cell carcinoma in non-smoking and non-drinking patients: a clinicopathological and molecular study of 46 cases.

    PubMed

    Laco, Jan; Vosmikova, Hana; Novakova, Vendula; Celakovsky, Petr; Dolezalova, Helena; Tucek, Lubos; Nekvindova, Jana; Vosmik, Milan; Cermakova, Eva; Ryska, Ales

    2011-02-01

    The aim of the study was to investigate the role of high-risk human papillomavirus (HR-HPV) infection in the etiopathogenesis of oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinoma in non-smoking and non-drinking patients (NSNDP). Twenty-four OSCCs and 22 OPSCCs were analyzed by immunohistochemistry for p16(INK4a) protein (p16) expression and by chromogene in situ hybridization (CISH) and polymerase chain reaction (PCR) for HR-HPV DNA presence. The series included 23 males and 23 females aged 35-93 years. p16 expression was seen in 7 out of 24 (29%) OSCCs and in 22 out of 22 (100%) OPSCCs. Using CISH, HR-HPV DNA was observed in 6 out of 24 (25%) OSCCs and in 21 out of 22 (95%) OPSCCs. HPV DNA was found in 3 out of 24 (13%) OSCCs and in 18 out of 22 (82%) OPSCCs using PCR. HPV 16 and 33 were detected in 16 and in two cases, respectively. Compared with OSCCs, OPSCCs more frequently showed basaloid morphology (p < 0.0001), lymph node involvement (p = 0.0063), diffuse p16 expression (p < 0.0001), HR-HPV DNA presence using both CISH and PCR (p < 0.0001; p < 0.0001), and better outcome. The sensitivity and specificity of p16 expression for HR-HPV DNA presence detected by CISH were 0.89 and 0.95, respectively, and 0.95 and 0.85 for PCR detected HPV DNA. The sensitivity and specificity of CISH for PCR detected presence of HPV DNA were 1.00 and 0.73, respectively. Our study is the first larger study analyzing OSCC and OPSCC in NSNDP. Our results indicate that unlike OSCC, a vast majority of OPSCCs may be associated with HR-HPV infection.

  1. Automated Extraction of Formalin-Fixed, Paraffin-Embedded Tissue for High-Risk Human Papillomavirus Testing of Head and Neck Squamous Cell Carcinomas Using the Roche Cobas 4800 System.

    PubMed

    Kerr, Darcy A; Sweeney, Brenda; Arpin, Ronald N; Ring, Melissa; Pitman, Martha B; Wilbur, David C; Faquin, William C

    2016-08-01

    -Testing for high-risk human papillomavirus (HR-HPV) in head and neck squamous cell carcinomas (HNSCCs) is important for both prognostication and clinical management. Several testing platforms are available for HR-HPV; however, effective alternative automated approaches are needed. -To assess the performance of the automated Roche cobas 4800 HPV real-time polymerase chain reaction-based system on formalin-fixed, paraffin-embedded HNSCC specimens and compare results with standard methods of in situ hybridization (ISH) and p16 immunohistochemistry. -Formalin-fixed, paraffin-embedded samples of HNSCC were collected from archival specimens in the Department of Pathology, Massachusetts General Hospital (Boston), and prepared using the automated system by deparaffinization and dehydration followed by tissue lysis. Samples were integrated into routine cervical cytology testing runs by cobas. Corresponding formalin-fixed, paraffin-embedded samples were evaluated for HR-HPV by ISH and p16 by immunohistochemistry. Discrepant cases were adjudicated by polymerase chain reaction. -Sixty-two HNSCC samples were analyzed using the automated cobas system, ISH, and immunohistochemistry. Fifty-two percent (n = 32 of 62) of formalin-fixed, paraffin-embedded tumors were positive for HR-HPV by cobas. Eighty-eight percent (n = 28 of 32) of cases were the HPV 16 subtype and 12% (n = 4 of 32) were other HR-HPV subtypes. Corresponding testing with ISH was concordant in 92% (n = 57 of 62) of cases. Compared with the adjudication polymerase chain reaction standard, there were 3 false-positive cases by cobas. -Concordance in HNSCC HR-HPV status between cobas and ISH was more than 90%. The cobas demonstrated a sensitivity of 100% and a specificity of 91% for detection of HR-HPV. Advantages favoring cobas include its automation, cost efficiency, objective results, and ease of performance.

  2. Increased expression of programmed death (PD)-1 and its ligand PD-L1 correlates with impaired cell-mediated immunity in high-risk human papillomavirus-related cervical intraepithelial neoplasia.

    PubMed

    Yang, Wen; Song, Yan; Lu, Yun-Long; Sun, Jun-Zhong; Wang, Hong-Wei

    2013-08-01

    Impaired local cellular immunity contributes to the pathogenesis of persistent high-risk human papillomavirus (HR-HPV) infection and related cervical intraepithelial neoplasia (CIN), but the underlying molecular mechanisms remain unclear. Recently, the programmed death 1/programmed death 1 ligand (PD-1/PD-L1; CD279/CD274) pathway was demonstrated to play a critical role in attenuating T-cell responses and promoting T-cell tolerance during chronic viral infections. In this study, we examined the expression of PD-1 and PD-L1 on cervical T cells and dendritic cells (DCs), respectively, from 40 women who were HR-HPV-negative (-) or HR-HPV-positive (+) with CIN grades 0, I and II-III. We also measured interferon-γ, interleukin-12 (IL-12) and IL-10 in cervical exudates. The most common HPV type was HPV 16, followed by HPV 18, 33, 51 and 58. PD-1 and PD-L1 expression on cervical T cells and DCs, respectively, was associated with HR-HPV positivity and increased in parallel with increasing CIN grade. The opposite pattern was observed for CD80 and CD86 expression on DCs, which decreased in HR-HPV+ patients in parallel with increasing CIN grade. Similarly, reduced levels of the T helper type 1 cytokines interferon-γ and IL-12 and increased levels of the T helper type 2 cytokine IL-10 in cervical exudates correlated with HR-HPV positivity and CIN grade. Our results suggest that up-regulation of the inhibitory PD-1/PD-L1 pathway may negatively regulate cervical cell-mediated immunity to HPV and contribute to the progression of HR-HPV-related CIN. These results may aid in the development of PD-1/PD-L1 pathway-based strategies for immunotherapy of HR-HPV-related CIN.

  3. MassARRAY Spectrometry Is More Sensitive than PreTect HPV-Proofer and Consensus PCR for Type-Specific Detection of High-Risk Oncogenic Human Papillomavirus Genotypes in Cervical Cancer▿

    PubMed Central

    Basu, Partha; Chandna, Puneet; Bamezai, R. N. K.; Siddiqi, Maqsood; Saranath, Dhananjaya; Lear, Adrian; Ratnam, Sam

    2011-01-01

    Type-specific detection of human papillomavirus (HPV) is indicated for better risk stratification and clinical management of women testing positive for HPV and for epidemiologic surveillance. MassARRAY spectrometry (MassARRAY; Sequenom) is a novel method for type-specific detection of 15 high-risk oncogenic HPV types: HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, -68, and -73. PreTect HPV-Proofer (Proofer; Norchip) is a type-specific assay that detects E6/E7 mRNA from five high-risk oncogenic HPV types: HPV-16, -18, -31, -33, and -45. The performance of these tests for type-specific identification of HPV was assessed with cervical specimens from 192 cases of cervical cancer in comparison with consensus MY09/MY11 PCR followed by nucleotide sequencing (consensus PCR). The overall HPV detection rates were 94.8% (95% confidence interval [CI], 91.7, 97.9), 83.3% (95% CI, 78.1, 88.5), and 86.5% (95% CI, 81.7, 91.3) for MassARRAY, Proofer, and consensus PCR, respectively. All tests were negative in six (3.1%) of the 192 cases. Considering only the specimens that contained at least one of the five types targeted by Proofer, the detection rates were 96.6%, 91.4%, and 86.9% for MassARRAY, Proofer, and consensus PCR, respectively. MassARRAY detected multiple infections in 14.1%, Proofer detected multiple infections in 3.6%, and consensus PCR failed to detect any multiple infections. The agreement was highest at 86.0% (kappa = 0.76) between MassARRAY and Proofer and lowest at 81.8% (kappa = 0.69) between Proofer and consensus PCR. In conclusion, MassARRAY is a highly sensitive and accurate method for type-specific detection of oncogenic HPV in cervical cancer, with Proofer showing impressive performance. PMID:21813716

  4. MassARRAY spectrometry is more sensitive than PreTect HPV-Proofer and consensus PCR for type-specific detection of high-risk oncogenic human papillomavirus genotypes in cervical cancer.

    PubMed

    Basu, Partha; Chandna, Puneet; Bamezai, R N K; Siddiqi, Maqsood; Saranath, Dhananjaya; Lear, Adrian; Ratnam, Sam

    2011-10-01

    Type-specific detection of human papillomavirus (HPV) is indicated for better risk stratification and clinical management of women testing positive for HPV and for epidemiologic surveillance. MassARRAY spectrometry (MassARRAY; Sequenom) is a novel method for type-specific detection of 15 high-risk oncogenic HPV types: HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, -68, and -73. PreTect HPV-Proofer (Proofer; Norchip) is a type-specific assay that detects E6/E7 mRNA from five high-risk oncogenic HPV types: HPV-16, -18, -31, -33, and -45. The performance of these tests for type-specific identification of HPV was assessed with cervical specimens from 192 cases of cervical cancer in comparison with consensus MY09/MY11 PCR followed by nucleotide sequencing (consensus PCR). The overall HPV detection rates were 94.8% (95% confidence interval [CI], 91.7, 97.9), 83.3% (95% CI, 78.1, 88.5), and 86.5% (95% CI, 81.7, 91.3) for MassARRAY, Proofer, and consensus PCR, respectively. All tests were negative in six (3.1%) of the 192 cases. Considering only the specimens that contained at least one of the five types targeted by Proofer, the detection rates were 96.6%, 91.4%, and 86.9% for MassARRAY, Proofer, and consensus PCR, respectively. MassARRAY detected multiple infections in 14.1%, Proofer detected multiple infections in 3.6%, and consensus PCR failed to detect any multiple infections. The agreement was highest at 86.0% (kappa = 0.76) between MassARRAY and Proofer and lowest at 81.8% (kappa = 0.69) between Proofer and consensus PCR. In conclusion, MassARRAY is a highly sensitive and accurate method for type-specific detection of oncogenic HPV in cervical cancer, with Proofer showing impressive performance.

  5. Clinical validation of the HPV-risk assay, a novel real-time PCR assay for detection of high-risk human papillomavirus DNA by targeting the E7 region.

    PubMed

    Hesselink, A T; Berkhof, J; van der Salm, M L; van Splunter, A P; Geelen, T H; van Kemenade, F J; Bleeker, M G B; Heideman, D A M

    2014-03-01

    The HPV-Risk assay is a novel real-time PCR assay targeting the E7 region of 15 high-risk human papillomavirus (HPV) types (i.e., HPV16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, -67, and -68), and provides additional genotype information for HPV16 and HPV18. This study evaluated the clinical performance and reproducibility of the HPV-Risk assay with cervical scraping specimens and its utility with self-collected (cervico)vaginal specimens. The clinical performance of the HPV-Risk assay for cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) with cervical scraping specimens was evaluated by a noninferiority analysis, relative to high-risk HPV GP5+/6+ PCR, following international guidelines for HPV test requirements for cervical cancer screening. The HPV-Risk assay showed clinical sensitivity for CIN2+ of 97.1% (95% confidence interval [CI], 89.1 to 99.3%; 67/69 samples) and a clinical specificity for CIN2+ of 94.3% (95% CI, 92.5 to 95.7%; 777/824 samples). The clinical sensitivity and specificity were noninferior to those of GP5+/6+ PCR (noninferiority score test, P=0.006 and 0.0003, respectively). Intralaboratory reproducibility over time (99.5% [95% CI, 98.6 to 99.8%]; 544/547 samples, kappa=0.99) and interlaboratory agreement (99.2% [95% CI, 98.6 to 99.8%]; 527/531 samples, kappa=0.98) for the HPV-Risk assay with cervical scraping specimens were high. The agreement of the HPV-Risk assay results for self-collected (cervico)vaginal specimens and clinician-obtained cervical scraping specimens was also high, i.e., 95.9% (95% CI, 85.1 to 99.0%; 47/49 samples, kappa=0.90) for self-collected lavage samples and 91.6% (95% CI, 84.6 to 95.6%; 98/107 samples, kappa=0.82) for self-collected brush samples. In conclusion, the HPV-Risk assay meets the cross-sectional clinical and reproducibility criteria of the international guidelines for HPV test requirements and can be considered clinically validated for cervical screening purposes. The

  6. Comparative evaluation of three commercial systems for detection of high-risk human papillomavirus in cervical and vaginal ThinPrep PreservCyt samples and correlation with biopsy results.

    PubMed

    Binnicker, M J; Pritt, B S; Duresko, B J; Espy, M J; Grys, T E; Zarka, M A; Kerr, S E; Henry, M R

    2014-10-01

    Genital human papillomavirus (HPV) is the etiologic agent of more than 99% of all cervical cancers worldwide, with 14 genotypes being considered oncogenic or "high risk" because of their association with severe dysplasia and cervical carcinoma. Among these 14 high-risk types, HPV-16 and -18 account for approximately 70% of cervical cancers. The aim of this study was to evaluate three FDA-approved HPV nucleic acid-based tests for the ability to predict high-grade cervical intraepithelial neoplasias (CIN2 or worse) in corresponding tissue biopsy specimens. Residual specimens (total n = 793, cervical n = 743, vaginal n = 50) collected in ThinPrep PreservCyt medium with a cytologic result of ≥ atypical squamous cells of undetermined significance were tested by the Hybrid Capture 2 (HC2) assay (Qiagen, Gaithersburg, MD), the cobas HPV test (Roche Diagnostics, Indianapolis, IN), and the APTIMA HPV assay (Hologic, San Diego, CA). Genotyping for HPV-16 and HPV-18 was simultaneously performed by the cobas HPV test. Results were compared to cervical or vaginal biopsy findings, when they were available (n = 350). Among the 350 patients with corresponding biopsy results, 81 (23.1%) showed ≥ CIN2 by histopathology. The ≥ CIN2 detection sensitivity was 91.4% by the cobas and APTIMA assays and 97.5% by HC2 assay. The specificities of the cobas, APTIMA, and HC2 assays were 31.2, 42.0, and 27.1%, respectively. When considering only positive HPV-16 and/or HPV-18 genotype results, the cobas test showed a sensitivity and a specificity of 51.9 and 86.6%, respectively. While the HC2, cobas, and APTIMA assays showed similar sensitivities for the detection of ≥ CIN2 lesions, the specificities of the three tests varied, with the greatest specificity (86.6%) observed when the HPV-16 and/or HPV-18 genotypes were detected. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  7. [Papillomaviruses and human tumors].

    PubMed

    Vonka, V; Hamsíková, E; Sobotková, E; Smahel, M; Kitasato, H; Sainerová, H; Ludvíková, V; Zák, R; Kanka, J; Kolár, Z; Kovarík, J

    2000-12-01

    The report summarizes the main results obtained in the course of our research project. The results of immunological and epidemiological studies provide further proofs that human papillomaviruses (HPV) are the etiological agents in cervical neoplasia. In addition, they raise hopes that immunological methods may be utilized in diagnostics of cervical cancer and for monitoring the clinical course of this disease in the near future. Since the etiological relationship between HPV and cervical carcinoma seems to be proven beyond reasonable doubt, the development of prophylactic and therapeutic vaccines has become the dominant of the contemporary HPV reseach. For studying immune reactions against HPV-induced tumours we developed a model of HPV16-transformed rodent cells.

  8. Epigenetics of human papillomaviruses

    SciTech Connect

    Johannsen, Eric; Lambert, Paul F.

    2013-10-15

    Human papilllomaviruses (HPVs) are common human pathogens that infect cutaneous or mucosal epithelia in which they cause warts, self-contained benign lesions that commonly regress. The HPV life cycle is intricately tied to the differentiation of the host epithelium it infects. Mucosotropic HPVs are the most common sexually transmitted pathogen known to mankind. A subset of the mucosotropic HPVs, so-called high risk HPVs, is etiologically associated with numerous cancers of the anogenital tract, most notably the cervix, as well as a growing fraction of head and neck cancers. In these cancers, the HPV genome, which normally exists an a double stranded, circular, nuclear plasmid, is commonly found integrated into the host genome and expresses two viral oncogenes, E6 and E7, that are implicated in the development and maintainance of the cancers caused by these high risk HPVs. Numerous studies, primarily on the high risk HPV16, have documented that the methylation status of the viral genome changes not only in the context of the viral life cycle but also in the context of the progressive neoplastic disease that culminates in cancer. In this article, we summarize the knowledge gained from those studies. We also provide the first analysis of available ChIP-seq data on the occupancy of both epigentically modified histones as well as transcription factors on the high risk HPV18 genome in the context of HeLa cells, a cervical cancer-derived cell line that has been the subject of extensive analyses using this technique. - Highlights: • Methylation status of HPV genomes is dynamic. • Changes are seen in both the viral life cycle and neoplasia. • Histone modification status at LCR is predictive of transcription factor occupancy. • Novel transcription factor binding noted by ChIP-seq.

  9. Comparison of GP5+/6+-PCR and SPF10-line blot assays for detection of high-risk human papillomavirus in samples from women with normal cytology results who develop grade 3 cervical intraepithelial neoplasia.

    PubMed

    Hesselink, A T; van Ham, M A P C; Heideman, D A M; Groothuismink, Z M A; Rozendaal, L; Berkhof, J; van Kemenade, F J; Massuger, L A F G; Melchers, W J G; Meijer, C J L M; Snijders, P J F

    2008-10-01

    Using a case control approach, we performed a two-way comparison study between GP5+/6+-PCR and HPV SPF(10)-Line Blot 25 (SPF(10)) assays for detection of 14 types of high-risk human papillomavirus (hrHPV) in samples from women with normal cytology results who had or developed grade 3 cervical intraepithelial neoplasia (CIN 3). Samples were pooled from two cohorts, i.e., women participating in population-based screening and women attending a gynecological outpatient clinic. Cases (n = 45) were women with histologically confirmed CIN 3 diagnosed within a median follow-up time of 2.7 (range, 0.2 to 7.9) years. Control samples were from women (n = 264) who had developed CIN 1 lesions at maximum (median follow-up at 5.8 [range, 0 to 10] years). Identical numbers of cases tested positive for 1 or more of the 14 hrHPV types by both systems (40/45; McNemar; P = 1.0). Conversely, SPF(10) scored significantly more controls as hrHPV positive than did GP5+/6+-PCR (95/264 versus 29/264; McNemar; P < 0.001). Consequently, women with normal cytology results and an hrHPV GP5+/6+-PCR-positive test exhibited a risk of CIN 3 that was 4.5 times higher (odds ratio [OR], 65; 95% confidence interval [95%CI], 24 to 178) than that seen for women with an hrHPV-positive SPF(10) test (OR, 14; 95%CI, 5 to 38)). Similar results were obtained after analysis of both cohorts separately. Discrepancy analysis by viral load assessment for the most common discordant hrHPV types (HPV16, -18, and -52) showed that samples which were SPF(10) positive only for these types had viral loads significantly lower than those for samples that were positive by both assays (analysis of variance; P < or = 0.006). Our data indicate that GP5+/6+-PCR has a better clinical performance than SPF(10) for women who are diagnosed with CIN 3 after prior normal cytology results. The extra positivity scored by SPF(10) mainly involved infections characterized by low viral loads that do not result in CIN 3.

  10. Persistent high-risk human papillomavirus infections and other end-point markers of progressive cervical disease among women prospectively followed up in the New Independent States of the Former Soviet Union and the Latin American Screening study cohorts.

    PubMed

    Syrjänen, Kari; Shabalova, Irena; Naud, Paulo; Kozachenko, Vladimir; Derchain, Sophie; Zakharchenko, Sergej; Roteli-Martins, Cecilia; Nerovjna, Raisa; Longatto-Filho, Adhemar; Kljukina, Ludmila; Tatti, Silvio; Branovskaja, Marina; Hammes, Luciano Serpa; Branca, Margherita; Grunjberga, Valerija; Erzen, Mojca; Sarian, Luis Otavio; Juschenko, Anna; Costa, Silvano; Podistov, Jurij; Syrjänen, Stina

    2009-07-01

    New end points are needed in future human papillomavirus (HPV) vaccine efficacy studies that accurately predict disease progression. Potential intermediate end points were analyzed in the combined New Independent States of the Former Soviet Union (NIS) and the Latin American Screening (LAMS) study cohorts. Data files of 2 international screening trials, the NIS (n = 3187) and the LAMS (n = 12,114) study cohorts, were combined, and a subcohort of 1865 (n = 854 and n = 1011 for the NIS and the LAMS, respectively) women prospectively followed up for 19.7 (median, 22.2) months was analyzed for different intermediate end-point markers of disease progression to squamous intraepithelial lesion (SIL), cervical intraepithelial neoplasia grade 1 and higher (CIN1+), and CIN grade 2 and higher (CIN2+) as terminal events. : Altogether, 131 (7.0%), 90 (4.8%), and 39 (2.1%) cases progressed to SIL, CIN1+, and CIN2+, respectively, progression times being equal in the NIS (11.9, 16.8, and 19.6 months) and LAMS (13.6, 14.1, and 15.4 months) cohorts (P = 0.931, P = 0.335, and P = 0.535). The 2 most powerful end-point markers of disease progression to CIN2+ were high-grade squamous intraepithelial lesions based on Papanicolaou test results at 6-month (odds ratio [OR] = 47.1; 95% confidence interval [CI], 17.3-128.7) and 12-month (OR = 21.5; 95% CI, 5.1-90.8) follow-up visits, with longitudinal positive and negative predictive values of 42.1% and 98.0% (6 months) and 33.3% and 97.7% (12 months). Of the virological end points, more than 6 months of persistent high-risk HPV (HR-HPV) was the most powerful predictor of progression to CIN1+ (OR = 18.6; 95% CI, 2.5-136.5), with longitudinal positive and negative predictive values of 10.3% and 99.4%, respectively. No additional benefit was obtained using more than 12 months of persistent HR-HPV end point. High-grade squamous intraepithelial lesion based on a Papanicolaou test results at 6- or 12-month follow-up visits was the most powerful

  11. Incidence and duration of type-specific human papillomavirus infection in high-risk HPV-naïve women: results from the control arm of a phase II HPV-16/18 vaccine trial

    PubMed Central

    Ramanakumar, Agnihotram V; Naud, Paulo; Roteli-Martins, Cecilia M; de Carvalho, Newton S; de Borba, Paola C; Teixeira, Julio C; Blatter, Mark; Moscicki, Anna-Barbara; Harper, Diane M; Romanowski, Barbara; Tyring, Stephen K; Ramjattan, Brian; Schuind, Anne; Dubin, Gary; Franco, Eduardo L

    2016-01-01

    Objectives Persistence of human papillomaviruses (HPVs) is necessary for cervical carcinogenesis. We evaluated incidence and duration of type-specific HPV infections and the influence of age and number of sexual partners. Methods Data were obtained from 553 women (15–25 years), who were seronegative and DNA-negative for high-risk HPV (HR-HPV) types and were enrolled in the placebo arm of a randomised trial of the HPV-16/18 vaccine (NCT00689741/NCT00120848). They were followed for 6.3 years. Cervicovaginal samples were self-collected at 3-month intervals for up to 27 months, and cervical samples were collected by clinicians at 6-month intervals until study end. Samples were tested for HPV types using a broad-spectrum PCR assay. Incidence rate ratios (RRs) and 95% CIs were used to estimate the association among age, sexual habits and HPV acquisition. Results Incidence rates (95% CI) using cervical samples were 11.8 (10.4 to 13.4) and 5.6 (4.7 to 6.6) per 1000 women-months for HR-HPVs and low-risk HPVs (LR-HPVs), respectively. Equivalent rates in combined cervicovaginal and cervical samples were 17.2 (15.4 to 19.2) and 6.9 (5.9 to 8.0), respectively. 54 per cent of HR-HPV types from combined cervicovaginal and cervical samples persisted for 1 year compared with 32.3% for LR-HPV types. The risk of acquiring any HPV infection was higher among women aged <21 years (RR=1.33, 95% CI 1.1 to 1.7) and women having >1 sexual partner (RR=1.83, 95% CI 1.4 to 2.4) at baseline. Conclusions HR-HPV infections were more common and lasted longer on average than LR-HPV infections. HPV acquisition was more common in younger women with multiple sexual partners. Trial registration number NCT00689741, NCT00120848; Post-results. PMID:27566633

  12. Prospective evaluation of the Hybrid Capture 2 and AMPLICOR human papillomavirus (HPV) tests for detection of 13 high-risk HPV genotypes in atypical squamous cells of uncertain significance.

    PubMed

    Halfon, Philippe; Trepo, Elisabeth; Antoniotti, Gilles; Bernot, Catherine; Cart-Lamy, Philippe; Khiri, Hacène; Thibaud, Didier; Marron, Jean; Martineau, Agnès; Pénaranda, Guillaume; Benmoura, Dominique; Blanc, Bernard

    2007-02-01

    The use of high-risk human papillomavirus (hrHPV) testing as an adjunct to cervical cytology in population-based screening programs is currently based on DNA hybridization and PCR assays. The aim of this study was to prospectively assess the diagnostic performance of the Hybrid Capture 2 test (HC2; Digene Corporation) in comparison with that of the recently developed PCR-based AMPLICOR HPV test (Roche Molecular Systems) for the detection of 13 hrHPV types. A reverse line blot hybridization assay (Innogenetics) was used as an internal reference standard in discordant cases. Two hundred seventy-one patients with atypical squamous cells of uncertain significance (ASCUS) in cervical samples underwent hrHPV testing. The chi-square test was performed to compare respective proportions. Totals of 160/271 (59%) and 156/271 (58%) were found to be positive for hrHPV with HC2 and AMPLICOR, respectively. Concordant results were obtained for 235 (86.7%) of the 271 samples (kappa statistic, 0.73 +/- 0.04). Considering types 26, 53, and 66 as oncogenic types, negative predictive values (NPVs) of HC2 and AMPLICOR were 92.8% and 87.8%, respectively (difference was not significant), and their respective accuracies were 94.8% and 91.9% (difference was not significant). Considering types 26, 53, and 66 as not oncogenic, the respective HC2 and AMPLICOR NPVs were 92.8% and 97.4% (difference was not significant), and accuracy was significantly higher for the AMPLICOR assay (95.9% versus 90.8% for HC2) (P<0.05). For ASCUS samples, the NPV was 92.8% for HC2 testing and might be compromised if the copy number of HPV DNA was low. The NPV was 97.4% for the AMPLICOR assay and might be compromised if HPV types 26, 53, and 66 were considered oncogenic. The accuracy of these two assays is good and is compatible with routine clinical use in the triage of ASCUS cases.

  13. High-risk human papillomavirus detection in self-sampling compared to physician-taken smear in a responder population of the Dutch cervical screening: Results of the VERA study.

    PubMed

    Ketelaars, P J W; Bosgraaf, R P; Siebers, A G; Massuger, L F A G; van der Linden, J C; Wauters, C A P; Rahamat-Langendoen, J C; van den Brule, A J C; IntHout, J; Melchers, W J G; Bekkers, R L M

    2017-08-01

    In 2017 the cervical cancer screening program in The Netherlands will be revised. Cervical smears will primarily be tested for the presence of high-risk human papillomavirus (hrHPV) instead of cytology, and vaginal self-sampling will be offered to non-responders. This includes a potential risk that part of the women who would otherwise opt for a cervical smear will wait for self-sampling. However, self-sampling for hrHPV in a responder population has never been studied yet. The aim of this study was to investigate the applicability and accuracy of self-sampling in detecting hrHPV in a screening responder population. A total of 2049 women, aged 30-60years, participating in the screening program in The Netherlands were included from April 2013 to May 2015. After they had their cervical smear taken, women self-collected a cervicovaginal sample with a brush-based device, the Evalyn Brush. Both the cervical smear and self-sample specimen were tested with the COBAS 4800 HPV platform. The hrHPV prevalence was 8.0% (95% CI 6.9-9.2) among the physician-taken samples, and 10.0% (95% CI 8.7-11.3) among the self-samples. There was 96.8% (95% CI 96.0-97.5) concordance of hrHPV prevalence between self-samples and physician-taken samples. Women in our study evaluated self-sampling as convenient (97.1%), user-friendly (98.5%), and 62.8% preferred self-sampling over a physician-taken sampling for the next screening round. In conclusion, self-sampling showed high concordance with physician-taken sampling for hrHPV detection in a responder screening population and highly acceptable to women. Implementation of HPV-self-sampling for the responder population as a primary screening tool may be considered. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Human papillomaviruses and skin cancer.

    PubMed

    Smola, Sigrun

    2014-01-01

    Human papillomaviruses (HPVs) infect squamous epithelia and can induce hyperproliferative lesions. More than 120 different HPV types have been characterized and classified into five different genera. While mucosal high-risk HPVs have a well-established causal role in anogenital carcinogenesis, the biology of cutaneous HPVs is less well understood. The clinical relevance of genus beta-PV infection has clearly been demonstrated in patients suffering from epidermodysplasia verruciformis (EV), a rare inherited disease associated with ahigh rate of skin cancer. In the normal population genus beta-PV are suspected to have an etiologic role in skin carcinogenesis as well but this is still controversially discussed. Their oncogenic potency has been investigated in mouse models and in vitro. In 2009, the International Agency for Research on Cancer (IARC) classified the genus beta HPV types 5 and 8 as "possible carcinogenic" biological agents (group 2B) in EV disease. This chapter will give an overview on the knowns and unknowns of infections with genus beta-PV and discuss their potential impact on skin carcinogenesis in the general population.

  15. Human Papillomavirus (HPV) and Oropharyngeal Cancer

    MedlinePlus

    ... Search Form Controls Cancel Submit Search the CDC Human Papillomavirus (HPV) Note: Javascript is disabled or is ... message, please visit this page: About CDC.gov . Human Papillomavirus (HPV) Facts & Brochures HPV Fact Sheet HPV & ...

  16. Emerging human papillomavirus vaccines

    PubMed Central

    Ma, Barbara; Maraj, Bharat; Tran, Nam Phuong; Knoff, Jayne; Chen, Alexander; Alvarez, Ronald D; Hung, Chien-Fu; Wu, T.-C.

    2013-01-01

    Introduction Identification of human papillomavirus (HPV) as the etiologic factor of cervical, anogenital, and a subset of head and neck cancers has stimulated the development of preventive and therapeutic HPV vaccines to control HPV-associated malignancies. Excitement has been generated by the commercialization of two preventive L1-based vaccines, which use HPV virus-like particles (VLPs) to generate capsid-specific neutralizing antibodies. However, factors such as high cost and requirement for cold chain have prevented widespread implementation where they are needed most. Areas covered Next generation preventive HPV vaccine candidates have focused on cost-effective stable alternatives and generating broader protection via targeting multivalent L1 VLPs, L2 capsid protein, and chimeric L1/L2 VLPs. Therapeutic HPV vaccine candidates have focused on enhancing T cell-mediated killing of HPV-transformed tumor cells, which constitutively express HPV-encoded proteins, E6 and E7. Several therapeutic HPV vaccines are in clinical trials. Expert opinion Although progress is being made, cost remains an issue inhibiting the use of preventive HPV vaccines in countries that carry the majority of the cervical cancer burden. In addition, progression of therapeutic HPV vaccines through clinical trials may require combination strategies employing different therapeutic modalities. As research in the development of HPV vaccines continues, we may generate effective strategies to control HPV-associated malignancies. PMID:23163511

  17. Human papillomavirus vaccine development.

    PubMed

    Fife, K H

    1998-11-01

    The greatest successes in combating important viral infections have been achieved using vaccines. A vaccine to prevent genital tract human papillomavirus (HPV) infections, especially those types associated with genital tract malignancy, could significantly reduce morbidity and mortality from cervical and other genital tract cancers. However, several barriers currently stand in the way of HPV vaccine development. The immunological response to natural HPV infection is incompletely understood and there is uncertainty about which viral antigen(s) should be included in a candidate vaccine. It is clear that immunization of several animal species with the L1 major capsid protein (usually in the form of virus-like particles) spurs the production of anti-HPV antibodies that are neutralizing in several assay systems. However, it is not clear if neutralizing antibody will be present in the genital tract in sufficient quantities to block infection. A second problem is the lack of a reliable serological assay for HPV. This is a major problem for clinical trials in which the identification of susceptible individuals, and incident infections, usually relies on serological diagnosis. Finally, there is also interest in the development of a vaccine that is used to treat individuals who are already infected--a therapeutic vaccine. It is likely that a therapeutic vaccine will need to target different or additional antigens to those comprising a prophylactic vaccine.

  18. Clinical significance of human papillomavirus genotyping.

    PubMed

    Choi, Youn Jin; Park, Jong Sup

    2016-03-01

    Cervical cancer is the fourth most common cancer in women worldwide, and the human papillomavirus (HPV) is the main causative agent for its development. HPV is a heterogeneous virus, and a persistent infection with a high-risk HPV contributes to the development of cancer. In recent decades, great advances have been made in understanding the molecular biology of HPV, and HPV's significance in cervical cancer prevention and management has received increased attention. In this review, we discuss the role of HPV genotyping in cervical cancer by addressing: clinically important issues in HPV virology; the current application of HPV genotyping in clinical medicine; and potential future uses for HPV genotyping.

  19. Human Papillomavirus Vaccine

    PubMed Central

    Savas, Lara S.; Fernández, Maria E.; Jobe, David; Carmack, Chakema C.

    2012-01-01

    Background Research is needed to understand parental factors influencing human papillomavirus (HPV) vaccination, particularly in groups with a higher burden of cervical cancer. Purpose To determine correlates of HPV vaccination among a sample of low-income parents of age-eligible daughters (aged 9–17 years) who called the 2-1-1 Helpline. Secondary analyses describe potential differences in HPV vaccination correlates by Hispanic and black parent groups, specifically. Methods This 2009 cross-sectional feasibility survey of cancer prevention needs was conducted in Houston at the 2-1-1 Texas/United Way Helpline. In 2012, to examine the association between parental psychosocial, cognitive, and decisional factors and HPV vaccination uptake (one or two doses), bivariate and multivariable logistic regression analyses were conducted for minority parents and for Hispanic and black parent groups, separately. Results Lower rates of HPV vaccination uptake were reported among minority daughters of 2-1-1 callers (29% overall) compared with national and Texas rates. In final adjusted analysis, factors positively associated with HPV vaccination uptake included being offered the vaccination by a doctor or nurse, belief that the vaccine would prevent cervical cancer, and Hispanic ethnicity. Secondary analyses detected differences in factors associated with vaccination in Hispanic and black groups. Conclusions Findings indicate low levels of vaccination among 2-1-1 callers. Increased understanding of determinants of HPV vaccination in low-income minority groups can guide interventions to increase coverage. Because 2-1-1 informational and referral services networks reach populations considered medically underserved, 2-1-1 can serve as a community hub for informing development of and implementing approaches aimed at hard-to-reach groups. PMID:23157770

  20. Human Papillomavirus Laboratory Testing: the Changing Paradigm

    PubMed Central

    2016-01-01

    SUMMARY High-risk human papillomaviruses (HPVs) cause essentially all cervical cancers, most anal and oropharyngeal cancers, and some vaginal, vulvar, and penile cancers. Improved understanding of the pathogenesis of infection and the availability of newer tests are changing the approach to screening and diagnosis. Molecular tests to detect DNA from the most common high-risk HPVs are FDA approved for use in conjunction with cytology in cervical cancer screening programs. More-specific tests that detect RNA from high-risk HPV types are now also available. The use of molecular tests as the primary screening tests is being adopted in some areas. Genotyping to identify HPV16 and -18 has a recommended role in triaging patients for colposcopy who are high-risk HPV positive but have normal cytology. There are currently no recommended screening methods for anal, vulvar, vaginal, penile, or oropharyngeal HPV infections. HPV testing has limited utility in patients at high risk for anal cancer, but p16 immunohistochemistry is recommended to clarify lesions in tissue biopsy specimens that show moderate dysplasia or precancer mimics. HPV testing is recommended for oropharyngeal squamous cell tumors as a prognostic indicator. Ongoing research will help to improve the content of future guidelines for screening and diagnostic testing. PMID:26912568

  1. Role of human papillomaviruses in carcinogenesis

    PubMed Central

    Ghittoni, Raffaella; Accardi, Rosita; Chiocca, Susanna; Tommasino, Massimo

    2015-01-01

    The human papillomavirus (HPV) family comprises more than 170 different types that preferentially infect the mucosa of the genitals, upper-respiratory tract, or the skin. The ‘high-risk HPV type’, a sub-group of mucosal HPVs, is the cause of approximately 5% of all human cancers, which corresponds to one-third of all virus-induced tumours. Within the high-risk group, HPV16 is the most oncogenic type, being responsible for approximatively 50% of all worldwide cervical cancers. Many studies suggest that, in addition to the high-risk mucosal HPV types, certain cutaneous HPVs also have a role in the development of non-melanoma skin cancer (NMSC). Functional studies on the HPV early gene products showed that E6 and E7 play a key role in carcinogenesis. These two proteins use multiple mechanisms to evade host immune surveillance, allowing viral persistence, and to deregulate cell cycle and apoptosis control, thus facilitating the accumulation of DNA damage and ultimately cellular transformation. The demonstration that high-risk HPV types are the etiological agents of cervical cancer allowed the implementation in the clinical routine of novel screening strategies for cervical lesions, as well as the development of a very efficient prophylactic vaccine. Because of these remarkable achievements, there is no doubt that in the coming decades we will witness a dramatic reduction of cervical cancer incidence worldwide. PMID:25987895

  2. Human papillomavirus infections: epidemiology, pathogenesis, and host immune response.

    PubMed

    Tyring, S K

    2000-07-01

    Human papillomaviruses (HPVs) are ubiquitous and often cause lesions on the skin that come to the attention of the dermatologist. Skin lesions, or warts, often occur on the hands or soles of the feet and can cause embarrassment or discomfort. Genital HPV infections are transmitted by sexual contact. Infections associated with some HPV types have a high risk of progressing to carcinoma. This review discusses the molecular biology and genetics of human papillomaviruses and provides an overview of the virology, pathology, clinical manifestations, and host immune response to infection.

  3. [General aspects of structure, classification and replication of human papillomavirus].

    PubMed

    Santos-López, Gerardo; Márquez-Domínguez, Luis; Reyes-Leyva, Julio; Vallejo-Ruiz, Verónica

    2015-01-01

    Human papillomavirus (HPV) refers to a group of viruses which belongs to a larger group, commonly referred to as papillomaviruses. These viruses are taxonomically located in the Papillomaviridae family. Papillomaviruses are small, non-enveloped with a genome of double-stranded DNA and they have affinity for epithelial tissue. Many of them are associated with human infection; they induce benign lesions of the skin (warts) and mucous membranes (condylomas), but they are also associated with some epithelial malignancies, such as cervical cancer and other tumors of the urogenital tract. Papillomaviridae contains 16 genera, which are named with a Greek letter prefix and the termination papillomavirus, e.g., Alphapapillomavirus, Betapapillomavirus, etcetera. From the clinical point of view, human papillomaviruses infecting the genital tract (which are located in the genus Alphapapilomavirus) have been divided into two groups: those of low risk, associated with benign genital warts, and those of high risk, with oncogenic potential, which are the etiological agents of cervical cancer. In this paper we review some relevant aspects of the structure, replication cycle and classification of human papillomaviruses.

  4. Prevalence and genotyping of human papillomavirus infection in women with vulvodynia.

    PubMed

    Orlandi, Augusto; Francesconi, Arianna; Angeloni, Caterina; Palmieri, Giampiero; Fulvia, Gloria; Ciotti, Marco; Criscuolo, Anna; Sesti, Francesco; Spagnoli, Luigi Giusto

    2007-01-01

    Evidence of vulvar human papillomavirus infection varies and the frequency of the different genotypes has not been adequately assessed. Fifty consecutive sexually active healthy patients with vulvodynia and suspected of human papillomavirus infection underwent a vulvoscopy and biopsy. Ten normal vulvar samples were also enrolled as control. Histological and vulvoscopic findings were compared in relation to human papillomavirus-DNA presence and genotyping by a broad-spectrum polymerase chain reaction and reverse hybridization line probe assay. Although the clinical and histological diagnoses did not always coincide, a good association was found (p<0.0001). Human papillomavirus-DNA was detected in 42% of all biopsies and in none of the controls, and less frequently in acetowhite-positive patients (33.3%, p<0.03). Squamous papillomatosis (74%) was the most frequent histological diagnosis, followed by condyloma (20%). Condyloma (90%) but not squamous papillomatosis (29.7%) was significantly associated with human papillomavirus-DNA presence. Out of the vulvoscopically normal patients, one (33%) was human papillomavirus-DNA positive. Out of the recorded microscopic features, only koilocytosis was associated with human papillomavirus-DNA presence. Eight different human papillomavirus genotypes were detected: high-risk 16 (43%), 31 (19%), 52 (14.3%), 68, and 59 (4.8% each), and low-risk types 6 (71.4%), 11, and 40 (4.8% each); 33.3% of infections were multiple, ranging from 2 to 4 genotypes. Out of the human papillomavirus-DNA positive squamous papillomatosis, 72.7% showed a high-risk type but the infection remained episomal. Our data confirm human papillomavirus as a frequent cause of vulvodynia and its frequent association with squamous papillomatosis or condyloma. The high-risk human papillomavirus in squamous papillomatosis suggests screening for possible undiagnosed cervical infection.

  5. Papilloma formation in human foreskin xenografts after inoculation of human papillomavirus type 16 DNA.

    PubMed Central

    Brandsma, J L; Brownstein, D G; Xiao, W; Longley, B J

    1995-01-01

    A mouse model of high-risk human papillomavirus infection was developed in which human papillomavirus (HPV) type 16 DNA was inoculated into human foreskin grafted to the skin of severe combined immunodeficient (scid) mice. Grafted skin contained human epidermis and dermis and, like normal human skin, expressed involucrin in differentiating keratinocytes. HPV type 16 DNA, attached to gold particles, was delivered directly into human epidermal cells and induced exophytic papilloma with histologic features of papillomavirus infection, including koilocytosis and expression of papillomavirus capsid antigen. This model should be useful for determining in vivo the functions of viral genes and for developing strategies to prevent and treat HPV-associated disease. It may also be of value in developing animal models of other human skin diseases. PMID:7884930

  6. Comparison of the novel human papillomavirus 4 auto-capillary electrophoresis test with the hybrid capture 2 assay and with the PCR HPV typing set test in the detection of high-risk HPV including HPV 16 and 18 genotypes in cervical specimens.

    PubMed

    Hong, Jin Hwa; Song, Seung Hun; Kim, Jong Kee; Han, Jeong Hyun; Lee, Jae Kwan

    2009-08-01

    The aim of this study was to compare the novel human papillomavirus (HPV) detection method, the HPV 4 Auto-capillary Electrophoresis (ACE) test with the hybrid capture (HC) 2 assay for the detection of high-risk HPVs. In addition, we compared the HPV 4 ACE test with the polymerase chain reaction HPV Typing Set test for the detection of HPV 16 and HPV 18 genotypes. One hundred ninety-nine cervical swab samples obtained from women with previous abnormal Pap smears were subjected to testing with the three HPV tests. The HPV 4 ACE test and the HC 2 assay showed substantial agreement for detection of high-risk HPVs (85.4%, kappa=0.71). The HPV 4 ACE test also showed substantial agreement with the PCR HPV Typing Set test in the detection of HPV 16 and HP V 18 genotypes (89.9%, kappa=0.65). In correlation with cytologic results, the sensitivities and specificities of the HPV 4 ACE test and HC 2 assay were 92.9% vs. 92.9% and 48.1% vs. 50.8%, respectively, when high-grade squamous intraepithelial lesions were regarded as abnormal cytologies. The novel HPV 4 ACE test is a valuable tool for the detection of high-risk HPVs and for genotyping of HPV 16 and HPV 18.

  7. Evaluation of immunological cross-reactivity between clade A9 high-risk human papillomavirus types on the basis of E6-Specific CD4+ memory T cell responses.

    PubMed

    van den Hende, Muriel; Redeker, Anke; Kwappenberg, Kitty M C; Franken, Kees L M C; Drijfhout, Jan W; Oostendorp, Jaap; Valentijn, A Rob P M; Fathers, Loraine M; Welters, Marij J P; Melief, Cornelis J M; Kenter, Gemma G; van der Burg, Sjoerd H; Offringa, Rienk

    2010-10-15

    CD4(+) T cell responses against the E6 oncoprotein of human papillomavirus (HPV) type 16 and 5 closely related members of clade A9 (HPV31, 33, 35, 52, and 58) were charted in peripheral blood mononuclear cell cultures from healthy subjects and patients who underwent HPV16 E6/E7-specific vaccination. Initial analyses with overlapping peptide arrays showed that approximately one-half of the responding subjects displayed reactivity against corresponding E6 peptides from >or=2 HPV types. This suggested immunological cross-reactivity and complicated retrospective evaluation of the infection history of the healthy subjects. Importantly, further dissection of the response by means of enriched and clonal T cell cultures (with protein antigen instead of peptides) revealed that CD4(+) T cells that are capable of efficiently reacting against E6 antigen from multiple HPV types are rare and only occur when epitope sequences are highly conserved. Our data indicate that natural and vaccine-induced HPV16 E6-specific CD4(+) T cell responses are unlikely to mediate efficient cross-protection against other clade A9 members.

  8. [Interpretation of guidance for establishing the performance characteristics of in vitro diagnostic devices for the detection or detection and differentiation of high-risk human papillomaviruses issued by Food and Drug Administration of United States and China].

    PubMed

    Feng, R M; Chen, W; Qiao, Y L

    2017-07-23

    To establish the standardization of clinical verification designs for in vitro diagnostic devices(IVDs) of human papillomavirus, China Food and Drug Administration (CFDA) and United States Food and Drug Administration (FDA) issued guidelines of detailed study designs and effectiveness evaluation for accuracy validation and clinical performance of nucleic acid detection, respectively, including triage of a typical squamous cells of undetermined significance(ASC-US) patients and validation of combined screening and preliminary screening. The design, study population, sample size estimation and statistical analysis of guidelines were moderately different from America to China, however, the evaluation indication was similar. According to the guideline issued by CFDA, prospective design suggested by FDA could be replaced by cross sectional study design to validate the triage of ASC-US patients. Alternatively, prospective design could be used to conduct the HPV product declaration and cellular parallel detection for the same natural population, and the clinical effectiveness of declared products could be validated by at least 3 years follow-up of cytology.

  9. Oral Human Papillomavirus Infection in Children.

    PubMed

    Ilea, Aranka; Boşca, Bianca; Miclăuş, Viorel; Rus, Vasile; Băbţan, Anida Maria; Mesaros, Anca; Crişan, Bogdan; Câmpian, Radu Septimiu

    2016-02-01

    Oral human papillomavirus infection is rare in children, but the presence of a villous lesion with slow but continuous growth concerns parents, who need information and therapeutic solutions from the physician. All these aspects are discussed based on a case report of a 9-year-old child with an oral human papillomavirus infection.

  10. Determinants of Viral Oncogene E6-E7 mRNA Overexpression in a Population-Based Large Sample of Women Infected by High-Risk Human Papillomavirus Types

    PubMed Central

    Bisanzi, Simonetta; Allia, Elena; Mongia, Alessandra; Carozzi, Francesca; Gillio-Tos, Anna; De Marco, Laura; Ronco, Guglielmo; Gustinucci, Daniela; Del Mistro, Annarosa; Frayle, Helena; Iossa, Anna; Fantacci, Giulia; Pompeo, Giampaolo; Cesarini, Elena; Bulletti, Simonetta; Passamonti, Basilio; Rizzi, Martina; Penon, Maria Gabriella; Barca, Alessandra; Benevolo, Maria

    2017-01-01

    ABSTRACT Cervical cancer screening by human papillomavirus (HPV) DNA testing with cytology triage is more effective than cytology testing. Compared to cytology, the HPV DNA test's higher sensitivity, which allows better protection with longer intervals, makes it necessary to triage the women with a positive result to compensate its lower specificity. We are conducting a large randomized clinical trial (New Technologies for Cervical Cancer 2 [NTCC2]) within organized population-based screening programs in Italy using HPV DNA as the primary screening test to evaluate, by the Aptima HPV assay (Hologic), the use of HPV E6-E7 mRNA in a triage test in comparison to cytology. By the end of June 2016, data were available for 35,877 of 38,535 enrolled women, 2,651 (7.4%) of whom were HPV DNA positive. Among the samples obtained, 2,453 samples were tested also by Aptima, and 1,649 (67.2%) gave a positive result. The proportion of mRNA positivity was slightly higher among samples tested for HPV DNA by the Cobas 4800 HPV assay (Roche) than by the Hybrid Capture 2 (HC2) assay (Qiagen). In our setting, the observed E6-E7 mRNA positivity rate, if used as a triage test, would bring a rate of immediate referral to colposcopy of about 4 to 5%. This value is higher than that observed with cytology triage for both immediate and delayed referrals to colposcopy. By showing only a very high sensitivity and thus allowing a longer interval for HPV DNA-positive/HPV mRNA-negative women, a triage by this test might be more efficient than by cytology. PMID:28100595

  11. Pathogenesis of infection by human papillomavirus.

    PubMed

    Brendle, Sarah A; Bywaters, Stephanie M; Christensen, Neil D

    2014-01-01

    Human papillomaviruses (HPVs) are associated with benign lesions known as warts and several cancer types including cancer of the cervix, penis, anus and oral cavity. HPVs are classified by their oncogenic potential and are divided into high-risk oncogenic HPVs and low-risk HPVs. Tissue tropism is used as another means of classifying the virus, and HPVs are divided into types that infect mucosal or cutaneous tissues. Several risk factors have been identified that elevate an individual's likelihood of becoming infected with HPV including cigarette smoking, a large number of lifetime sexual partners and immunosuppression. Most HPV infections are cleared naturally, although persistent infection with oncogenic HPV types can lead to the cancers mentioned above. HPV has employed several mechanisms to avoid detection by the host immune system. Virus is released along with shedding skin cells in a nonlytic manner, and the virus has an altered codon usage leading to reduced expression of viral proteins. Infections from high-risk oncogenic HPV types that progress cause neoplasias that are defined as CIN1-CIN3 depending on the amount of abnormal cell growth and the level of cellular differentiation.

  12. Human papillomavirus type 18 infection in a female renal allograft recipient: a case report.

    PubMed

    Cistjakovs, Maksims; Sultanova, Alina; Jermakova, Olga; Chapenko, Svetlana; Lesina-Korne, Baiba; Rozental, Rafail; Razeberga, Dace; Murovska, Modra; Ziedina, Ieva

    2016-11-09

    Human papillomavirus type 18 is the second most common cause of cervical cancer and is found in 7 to 20 % of cases of cervical cancer. The oncogenic potential of high-risk human papillomavirus is associated with expression of early proteins E6 and E7. Due to long-term immunosuppressive therapy, renal transplant recipients have a higher risk of developing persistent human papillomavirus infection. A 29-year-old white woman from Latvia with chronic focal segmental glomerulosclerosis received renal allograft transplantation and was prescribed immunosuppressive therapy with cyclosporine, prednisolone, and mycophenolate mofetil. Two weeks after renal transplantation, her cervical swab was positive for human papillomavirus consensus sequences. After 6 months, quantitative polymerase chain reaction showed a high viral load of 3,630,789 copies/10(5) cells of high-risk human papillomavirus type 18 and expression of E6 and E7 oncogenes in her cervical swab and urine sample. One year after renal transplantation, the viral load in her cervical swab increased significantly to 7,413,102 copies/10(5) cells. Messenger ribonucleic acid of human papillomavirus type 18 E6 and E7 oncogenes were also detected. Shortly after this, she had an unsuccessful pregnancy which resulted in a spontaneous abortion at 6/7 weeks. Two months after the abortion her viral load sharply decreased to 39 copies/10(5) cells. Oncogenes E6 and E7 messenger ribonucleic acid expression was not observed in this period. This case report represents data which show that immunosuppressive therapy may increase the risk of developing persistent high-risk human papillomavirus infection with expression of E6 and E7 oncogenes in renal transplant recipients. However, even during this therapy the immune status of a recipient can improve and contribute to human papillomavirus viral load reduction. Spontaneous abortion can be considered a possible contributory factor in human papillomavirus clearance.

  13. [Human papillomavirus prophylactic vaccines: stakes and perspectives].

    PubMed

    Hantz, S; Alain, S; Denis, F

    2006-01-01

    Human Papillomavirus (HPV) infection is established as the necessary cause of cervical precancers and cancers. To date, more than 120 genotypes are known, but only high risk oncogen genotypes could induce a cancer. HPV 16 and 18 are implied in nearly 70% of cervical cancer around the world. Although some persistent HPV infections progress to cervical cancer, host immunity is generally able to clear most HPV infections providing an opportunity for cervical cancer prevention through vaccination. Candidate prophylactic vaccines based on papillomavirus L1 virus-like particles (VLPs) are currently on human clinical trials: one targeting cervical cancer with a bivalent VLP L1 vaccine containing the two genotypes most frequently involved in cervical cancer (type 16 and 18) and the other, protecting against warts as well as cervical cancer, with a quadrivalent HPV VLP L1 vaccine containing genotypes 6, 11, 16 and 18. The first clinical trials revealed the satisfactory tolerance and excellent immunogenicity of these vaccines inducing high serum antibody titers with minimal side effects. After more than three years, both clinical trials on women 15 to 25 years old have shown that vaccines are able to type specifically protect against nearly 90% of infection and all cervical intra-epithelial neoplasia. The vaccinal strategy defined to date targets preadolescents and adolescent young females (11-13 years) before the first sexual course but some questions are still not resolved concerning the prescriber, the actors of the vaccination and the duration of the protection. Nevertheless cervical cancer screening should be carried on for many years, even if a large vaccinal strategy is decided. Such a vaccine would save lives and reduce the need for costly medical procedures and the psychological stress induced by this cancer.

  14. Incidence of cervical human papillomavirus infection in systemic lupus erythematosus women.

    PubMed

    Mendoza-Pinto, C; García-Carrasco, M; Vallejo-Ruiz, V; Méndez-Martínez, S; Taboada-Cole, A; Etchegaray-Morales, I; Muñóz-Guarneros, M; Reyes-Leyva, J; López-Colombo, A

    2017-01-01

    Objectives Our objective was to study the incidence, persistence and clearance of human papillomavirus infection in systemic lupus erythematosus women and assess risk factors for persistence of human papillomavirus infection. Methods We carried out a prospective, observational cohort study of 127 systemic lupus erythematosus women. Patients were evaluated at baseline and at three years. Traditional and systemic lupus erythematosus women-related disease risk factors were collected. Gynaecological evaluations and cervical cytology screening were made. Human papillomavirus detection and genotyping were made by polymerase chain reaction and linear array. Results The cumulative prevalence of human papillomavirus infection increased from 22.8% at baseline to 33.8% at three years; p = < 0.001: 20.1% of patients experienced 43 incident infections. The risk of any human papillomavirus infection was 10.1 per 1000 patient-months. At three years, 47 (88.6%) prevalent infections were cleared. Independent risk factors associated with incident human papillomavirus infection included more lifetime sexual partners (odds ratio = 1.8, 95% confidence interval = 1.11-3.0) and cumulative cyclophosphamide dose (odds ratio = 3.9, 95% confidence interval = 1.2-12.8). Conclusions In systemic lupus erythematosus women, the cumulative prevalence of human papillomavirus infection, including high risk-human papillomavirus and multiple human papillomavirus infections, may increase over time. Most persistent infections were low risk-human papillomavirus. The number of lifetime sexual partners and the cumulative cyclophosphamide dose were independently associated with incident human papillomavirus infection.

  15. [Apoptosis modulation by human papillomavirus].

    PubMed

    Jave-Suárez, Luis Felipe; Ratkovich-González, Sarah; Olimón-Andalón, Vicente; Aguilar-Lemarroy, Adriana

    2015-01-01

    One of the most important processes to keep the homeostasis in organisms is the apoptosis, also called programmed cell death. This mechanism works through two pathways: The intrinsic or mitochondrial, which responds to DNA damage and extern agents like UV radiation; and the extrinsic or receptor-mediated, which binds to their ligands to initiate the apoptotic trail. The evasion of apoptosis is one of the main causes of cellular transformation to malignity. Many viruses had shown capacity to modify the apoptotic process; among them is the human papillomavirus, which, by means of its oncoproteins, interferes in pathways, reacting with the receptors and molecules and participating in the death mechanism. This creates ideal conditions for cancer development.

  16. Monitoring of human papillomavirus vaccination.

    PubMed

    Dillner, J; Arbyn, M; Unger, E; Dillner, L

    2011-01-01

    Persistent infection with oncogenic human papillomavirus (HPV) is a necessary causal factor in the development of cervical cancer. Moreover, HPV, predominately type 16 and to a lesser degree type 18, is linked causally to varying proportions of other anogenital cancers (vulva, vagina, penis, anus) as well as cancers elsewhere in the body (oropharynx, larynx, conjunctiva). HPV types 6 and 11 cause most of genital warts and recurrent respiratory papillomatosis. Effective prophylactic vaccines have been developed. In this review, we address briefly the immunological aspects of HPV infection and the results of HPV vaccination trials. Internationally standardized monitoring and evaluation of prophylactic HPV vaccination programmes will be essential for arriving at the most cost-effective strategies for cancer control. © 2010 The Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology.

  17. Monitoring of human papillomavirus vaccination

    PubMed Central

    Dillner, J; Arbyn, M; Unger, E; Dillner, L

    2011-01-01

    Persistent infection with oncogenic human papillomavirus (HPV) is a necessary causal factor in the development of cervical cancer. Moreover, HPV, predominately type 16 and to a lesser degree type 18, is linked causally to varying proportions of other anogenital cancers (vulva, vagina, penis, anus) as well as cancers elsewhere in the body (oropharynx, larynx, conjunctiva). HPV types 6 and 11 cause most of genital warts and recurrent respiratory papillomatosis. Effective prophylactic vaccines have been developed. In this review, we address briefly the immunological aspects of HPV infection and the results of HPV vaccination trials. Internationally standardized monitoring and evaluation of prophylactic HPV vaccination programmes will be essential for arriving at the most cost-effective strategies for cancer control. PMID:21062269

  18. Recombinant Human Papillomavirus (HPV) Quadrivalent Vaccine

    Cancer.gov

    This page contains brief information about recombinant human papillomavirus (HPV) quadrivalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.

  19. Identification of human papillomavirus in pterygium.

    PubMed

    Hamed-Azzam, Shirin; Edison, Natalia; Briscoe, Daniel; Mukari, Abed; Elmalah, Irit

    2016-05-01

    The purpose of this study was to evaluate the involvement of human papillomavirus in the pathogenesis of primary and recurrent pterygium in northern Israel. A retrospective study examined 100 randomly chosen pterygium specimens with solar elastosis, from 100 patients who underwent pterygium surgery during 2012-2013 at the Emek Medical Center. All the specimens were analysed for evidence of human papillomavirus infection by immunohistochemistry. Human papillomavirus was not detected in any of the 100 pterygia samples by immunohistochemistry. These used samples were taken from 100 patients with mean age of 51.5 years and a primary: recurrent ratio of 8.09:1. We conclude from our study that human papillomavirus infection does not appear to be an important pathogenic factor of pterygium in Israel. © 2015 Emek Medical Center.

  20. Recombinant Human Papillomavirus (HPV) Nonavalent Vaccine

    Cancer.gov

    This page contains brief information about recombinant human papillomavirus (HPV) nonavalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.

  1. Recombinant Human Papillomavirus (HPV) Quadrivalent Vaccine

    Cancer.gov

    This page contains brief information about recombinant human papillomavirus (HPV) quadrivalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.

  2. Recombinant Human Papillomavirus (HPV) Bivalent Vaccine

    Cancer.gov

    This page contains brief information about recombinant human papillomavirus (HPV) bivalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.

  3. Model systems of human papillomavirus-associated disease.

    PubMed

    Doorbar, John

    2016-01-01

    Human papillomaviruses (HPVs) cause a range of serious diseases, including the vast majority of cervical cancers, most anal cancers and around half of head and neck cancers. They are also responsible for troublesome benign epithelial lesions, including genital warts and laryngeal papillomas, and in some individuals HPVs lead to recurrent respiratory papillomatosis and other difficult-to-manage diseases. As a result, there is a great need for model systems that accurately mimic papillomavirus infections in humans. This is complicated by the diverse variety of HPVs, which now number over 200 types, and the different strategies they have evolved to persist in the population. The most well-developed models involve the culture of HPV-containing keratinocytes in organotypic raft culture, an approach which appears to accurately mimic the life cycle of several of the high-risk cancer-associated HPV types. Included amongst these are HPV16 and 18, which cause the majority of cervical cancers. The low-risk HPV types persist less well in tissue-culture models, and our ability to study the productive life cycle of these viruses is more limited. Although ongoing research is likely to improve this situation, animal models of papillomavirus disease can provide considerable basic information as to how lesions form, regress and can be controlled by the immune system. The best studied are cottontail rabbit papillomavirus, rabbit oral papillomavirus and, more recently, mouse papillomavirus (MmuPV), the last of which is providing exciting new insights into viral tropisms and immune control. In addition, transgenic models of disease have helped us to understand the consequences of persistent viral gene expression and the importance of co-factors such as hormones and UV irradiation in the development of neoplasia and cancer. It is hoped that such disease models will eventually lead us to better understanding and better treatments for human disease.

  4. Human Papillomaviruses As Therapeutic Targets in Human Cancer

    PubMed Central

    Hellner, Karin; Münger, Karl

    2011-01-01

    Cervical carcinomas are almost universally associated with high-risk human papillomavirus (HPV) infections, and are a leading cause of cancer death in women worldwide. HPV oncoproteins contribute to cancer initiation and progression and their expression is necessary for the maintenance of the transformed state. The fact that the initiating oncogenic insult, infection with a high-risk HPV and viral oncoprotein expression, is common to almost all cervical cancers offers unique opportunities for prevention, early detection, and therapy. The potential for prevention has been realized by introduction of prophylactic vaccines that are to prevent transmission of specific high-risk HPVs. Given, however, that these vaccines have no therapeutic efficacy and HPV-associated cervical cancers arise years if not decades after the initial infection, it has been estimated that there will be no measurable decline of HPV-associated tumors before 2040. Cervical cancer alone will be diagnosed in more than 375,000 US women between now and 2040. Other HPV-associated anogenital and head and neck cancers are predicted to afflict another 700,000 men and women over this time period. Hence, therapeutic efforts to combat high-risk HPV-associated disease remain of critical importance. PMID:21220591

  5. Evaluation of HIV and highly active antiretroviral therapy on the natural history of human papillomavirus infection and cervical cytopathologic findings in HIV-positive and high-risk HIV-negative women.

    PubMed

    Blitz, Sandra; Baxter, Joanna; Raboud, Janet; Walmsley, Sharon; Rachlis, Anita; Smaill, Fiona; Ferenczy, Alex; Coutlée, François; Hankins, Catherine; Money, Deborah

    2013-08-01

    The Canadian Women's HIV Study (CWHS) enrolled human immunodeficiency virus (HIV)-positive and high-risk HIV-negative women in a longitudinal cohort. This analysis considered the effects of HIV and highly active antiretroviral therapy (HAART) on HPV persistence and cervical squamous intraepithelial lesions (SILs). Longitudinal cytopathologic and HPV DNA results were analyzed using multistate models. States of cervical SIL were defined as absent, present, and treatment; HPV states were defined as negative or positive. Demographic variables and markers of sexual activity were considered predictors. Results were calculated on the basis of transition probabilities and reported as hazard ratios (HRs). The CWHS followed 750 HIV-positive and 323 HIV-negative women during 1993-2002. A total of 467 and 456 women were included in the longitudinal cervical cytopathologic and HPV DNA analyses, respectively. HIV-positive women had increased prevalence (46.6% vs 28.7%; P < .0001), increased acquisition (HR, 2.3; P = .03), and decreased clearance (HR, 0.4; P < .001) of oncogenic HPV as compared to HIV-negative women. Oncogenic HPV infection predicted progression of cervical dysplasia from normal to abnormal SIL (HR, 2.8; P = .002). Among HIV-positive participants, HAART increased the likelihood of regression (from present to absent) of cervical SIL (HR, 3.3; P = .02) and increased the clearance of oncogenic HPV types other than HPV-16 or HPV-18 (HR, 2.2; P = .01). This analysis demonstrated beneficial effects of HAART on cervical SIL in HIV-positive women.

  6. A comparison of clinically utilized human papillomavirus detection methods in head and neck cancer

    PubMed Central

    Schlecht, Nicolas F.; Brandwein-Gensler, Margaret; Nuovo, Gerard J.; Li, Maomi; Dunne, Anne; Kawachi, Nicole; Smith, Richard V.; Burk, Robert D.; Prystowsky, Michael B.

    2011-01-01

    Detection of human papillomavirus in head and neck cancer has therapeutic implications. In-situ hybridization and immuno-histochemistry for p16 are used by surgical pathologists. We compared the sensitivity and specificity of three popular commercial tests for human papillomavirus detection in head and neck squamous cell carcinomas to a “gold standard” human papillomavirus PCR assay. One hundred-and-ten prospectively collected, formalin fixed tumor specimens were compiled onto tissue microarrays and tested for human papillomavirus DNA by in-situ hybridization with two probe sets: a biotinylated probe for high-risk human papillomavirus types 16/18 (Dako, CA), and a probe cocktail for 16/18 plus 10 additional high-risk types (Ventana, AZ). P16INK4 expression was also assessed using a Pharmingen immuno-histochemistry antibody (BD Biosciences, CA). Tissue microarrays were stained and scored at expert laboratories. Human papillomavirus DNA was detected by MY09/11-PCR using Gold AmpliTaq and dot-blot hybridization on matched fresh frozen specimens in a research laboratory. Human papillomavirus 16 E6 and E7-RNA expression was also measured using RT-PCR. Test performance was assessed by receiver operating characteristic analysis. High-risk human papillomavirus DNA types 16, 18 and 35 were detected by MY-PCR in 28% of tumors, with the majority (97%) testing positive for type 16. Compared to MY-PCR, the sensitivity and specificity for high-risk human papillomavirus DNA detection with Dako in-situ hybridization was 21% (95%CI:7–42) and 100% (95%CI:93–100), respectively. Corresponding test results by Ventana in-situ hybridization were 59% (95%CI:39–78) and 58% (95%CI:45–71), respectively. P16 immuno-histochemistry performed better overall than Dako (p=0.042) and Ventana (p=0.055), with a sensitivity of 52% (95%CI:32–71) and specificity of 93% (95%CI:84–98). Compared to a gold standard human papillomavirus PCR assays, HPV detection by in-situ hybridization was

  7. The natural history of human papillomavirus infection.

    PubMed

    de Sanjosé, Silvia; Brotons, Maria; Pavón, Miguel Angel

    2017-09-06

    Human papillomavirus (HPV) is a small double-stranded DNA virus that commonly infects humans. The oncogenic characteristics of HPV derive from the oncoproteins E6 and E7 that act inhibiting p53 and pRB tumor suppressors. About 5% of all cancers worldwide are attributable mainly to those known as high-risk, including HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. Infection with HPV is common after sexual initiation, but the majority of HPV infections do not cause symptoms or disease and are cleared within 12-24 months post-infection. Only a small fraction of those infections that persist or progress to a preneoplastic lesion result in cancer. Persistence of HPV infection is needed to start the oncogenic process. Clearance of infection is common in young adults. Viral load and viral type are the main cofactors for progression from infection to cervical intraepithelial lesions and cancer. Smoking, hormonal exposure, and HIV are additional exposures that increase the risk of progression to cancer. The adverse health effects of HPV infections can be largely controlled through vaccination and screening. Copyright © 2017. Published by Elsevier Ltd.

  8. Immunoprevention of human papillomavirus-associated malignancies

    PubMed Central

    Wang1, Joshua W.; Hung, Chein-fu; Huh, Warner K.; Trimble, Cornelia L.; Roden, Richard B.S.

    2014-01-01

    Persistent infection by one of fifteen high risk human papillomavirus (hrHPV) types is a necessary but not sufficient cause of 5% of all human cancers. This provides a remarkable opportunity for cancer prevention via immunization. Since Harald zur Hausen’s pioneering identification of hrHPV types 16 and 18, found in ~50% and ~20% of cervical cancers respectively, two prophylactic HPV vaccines containing virus-like particles (VLP) of each genotype have been widely licensed. These vaccines are beginning to impact infection and HPV-associated neoplasia rates after immunization campaigns in adolescents. Here we review recent progress and opportunities to better prevent HPV-associated cancers, including: broadening immune-protection to cover all hrHPV types, reducing the cost of HPV vaccines especially for developing countries that have the highest rates of cervical cancer, and immune-based treatment of established HPV infections. Screening based upon George Papanicolaou’s cervical cytology testing, and more recently detection of hrHPV DNA/RNA, followed by ablative treatment of high grade cervical intraepithelial neoplasia (CIN2/3) have substantially reduced cervical cancer rates, and we examine their interplay with immune-based modalities for the prevention and eventual elimination of cervical cancer and other HPV-related malignancies. PMID:25488410

  9. The Association of High Risk Human Papillomaviruses in Patients With Cervical Cancer: An Evidence Based Study on Patients With Squamous Cell Dysplasia or Carcinoma for Evaluation of 23 Human Papilloma Virus Genotypes

    PubMed Central

    Piroozmand, Ahmad; Mostafavi Zadeh, Seyed Mostafa; Madani, Azita; Soleimani, Reza; Nedaeinia, Reza; Niakan, Mohammad; Avan, Amir; Manian, Mostafa; Moradi, Mohammad; Eftekhar, Zahra

    2016-01-01

    Background Cervical cancer is one of the leading causes of cancer-related death in females. Human papilloma virus (HPV) is the major risk factor of cervical cancer. Objectives The aim of the current study was to explore the frequency and role of 23 different HPVs in patients with cervical cancer. Materials and Methods Overall, 117 formalin-fix and paraffin-embedded (FFPE) tissues from cervical cancer patients with squamous cell carcinoma (SCC) or dysplasia were collected from Mirza-Kochakkhan-Jangali hospital, Tehran, Iran during year 2013, to investigate the presence of HPV- HPV- 67, 68, 6, 11, 13, 16, 17, 30, 69, 39, 40, 42, 64, 66 and 51 to 59 genotypes. Results The Pap smear report illustrated the presence of malignancy in 71 cases, while 11 cases had no evidence of malignancy. Among the patients, 26 cases had sexually transmitted disease with relative frequency of 0.58. Infection with papilloma virus was observed in 83.6% of SCC patients and 45% of the dysplasia group. The most prevalent HPV genotypes were 18 with 31.62% and 16 with 27.35% of cases. Moreover the relative frequencies of HPV-33, -6, -58, -52, -35 and -51, genotypes were 15.38, 7.69, 5.98, 5.12 and 3.41%, respectively. Among the different genotypes of HPV, 31 had the lowest and 16 had the highest relative frequency. Conclusions Our findings demonstrate that HPV-16 and -18 have a higher prevalence in our population than 31 and 51. Further investigations are required to evaluate the role of these genotypes in a larger multicenter setting for establishing their values for early detection of patients, which is useful for screening and vaccination programs of cancerous and precancerous lesions of cervical cancer. PMID:27279992

  10. Evidence and Impact of Human Papillomavirus Latency

    PubMed Central

    Gravitt, Patti E

    2012-01-01

    At present, there is no consensus in the scientific community regarding the ability for human papillomavirus (HPV) infections to establish latency. Based on animal studies, a model of papillomavirus latency has been proposed in which papillomaviruses can be retained in the basal epithelial stem cell pool as latent infections and periodically induced to reactivate when the stem cell divides and one daughter cell is committed to terminal differentiation and induction of the viral life cycle. Tissue resident memory T-cells are hypothesized to control these periodic reactivation episodes and thus limit their duration. In this paper, evidence from human studies consistent with this model of papillomavirus latency is reviewed. Given the strong circumstantial evidence supporting a natural history of HPV infection which includes a immunologically controlled latent state, the longer term implications of HPV latency on a highly infected and aging population may warrant a more serious evaluation. PMID:23341855

  11. Bovine and human papillomaviruses: a comparative review.

    PubMed

    Munday, J S

    2014-11-01

    Fifty years ago, inoculation with bovine papillomavirus (BPV) was found to cause mesenchymal tumors of the skin in cattle and horses, as well as tumors of the bladder in cattle. Subsequent to these studies of BPVs, human papillomaviruses (HPVs) were found to cause cervical cancer resulting in intense research into papillomaviruses. During the past 50 years, the ways that HPVs and BPVs cause disease have been investigated, and both HPVs and BPVs have been associated with an increasingly diverse range of diseases. Herein, the biology, oncogenic mechanisms, and diseases associated with BPVs are compared with those of HPVs. As reviewed, there are currently significant differences between BPVs and HPVs. However, research 50 years ago into BPVs formed a prologue for the recognition that papillomaviruses have a significant role in human disease, and it is possible that future research may similarly reveal that BPVs are less different from HPVs than is currently recognized. © The Author(s) 2014.

  12. [Human papillomavirus detection in cervical cancer prevention].

    PubMed

    Picconi, María Alejandra

    2013-01-01

    Cervical cancer (CC), which is strongly associated to high-risk human papillomavirus (hr-HPV) infection, continues being a significant health problem in Latin America. The use of conventional cytology to detect precancerous cervical lesions has had no major impact on reducing CC incidence and mortality rates, which are still high in the region. New screening tools to detect precancerous lesions became available, which provide great opportunities for CC prevention, as do highly efficacious HPV vaccines able to prevent nearly all lesions associated with HPV-16 and -18 when applied before viral exposure. Currently, hr-HPV testing represents an invaluable component of clinical guidelines for screening, management and treatment of CC and their precursor lesions. Many testing strategies have been developed that can detect a broad spectrum of hr-HPV types in a single assay; however, only a small subset of them has documented clinical performance for any of the standard HPV testing indications. HPV tests that have not been validated and lack proof of reliability, reproducibility and accuracy should not be used in clinical management. Once incorporated into the lab, it is essential to submit the whole procedure of HPV testing to continuous and rigorous quality assurance to avoid sub-optimal, potentially harmful practices. Recent progress and current status of these methods are discussed in this article.

  13. An update on oral human papillomavirus infection

    PubMed Central

    Bharti, Ankit H.; Chotaliya, Kiran; Marfatia, Y. S.

    2013-01-01

    Human papillomavirus (HPV) constitutes the majority of newly acquired sexually transmitted infections (STIs) in United States as per the centers for disease control factsheet 2013. Genital HPV is the most common STI with incidence of about 5.5 million world-wide, nearly 75% of sexually active men and women have been exposed to HPV at some point in their lives. Oral Sexual behavior is an important contributor to infection of HPV in the oral mucosa especially in cases known to practice high risk behavior and initiating the same at an early age. HPV infection of the oral mucosa currents is believed to affect 1-50% of the general population, depending on the method used for diagnosis. The immune system clears most HPV naturally within 2 years (about 90%), but the ones that persist can cause serious diseases. HPV is an essential carcinogen being implicated increasingly in association with cancers occurring at numerous sites in the body. Though there does not occur any specific treatment for the HPV infection, the diseases it causes are treatable such as genital warts, cervical and other cancers. PMID:24339456

  14. Therapeutic Vaccine Strategies against Human Papillomavirus

    PubMed Central

    Khallouf, Hadeel; Grabowska, Agnieszka K.; Riemer, Angelika B.

    2014-01-01

    High-risk types of human papillomavirus (HPV) cause over 500,000 cervical, anogenital and oropharyngeal cancer cases per year. The transforming potential of HPVs is mediated by viral oncoproteins. These are essential for the induction and maintenance of the malignant phenotype. Thus, HPV-mediated malignancies pose the unique opportunity in cancer vaccination to target immunologically foreign epitopes. Therapeutic HPV vaccination is therefore an ideal scenario for proof-of-concept studies of cancer immunotherapy. This is reflected by the fact that a multitude of approaches has been utilized in therapeutic HPV vaccination design: protein and peptide vaccination, DNA vaccination, nanoparticle- and cell-based vaccines, and live viral and bacterial vectors. This review provides a comprehensive overview of completed and ongoing clinical trials in therapeutic HPV vaccination (summarized in tables), and also highlights selected promising preclinical studies. Special emphasis is given to adjuvant science and the potential impact of novel developments in vaccinology research, such as combination therapies to overcome tumor immune suppression, the use of novel materials and mouse models, as well as systems vaccinology and immunogenetics approaches. PMID:26344626

  15. Current status of human papillomavirus vaccines

    PubMed Central

    Yi, Seokjae

    2014-01-01

    Cervical cancer is a malignant neoplasm arising from cells that originate in the cervix uteri. It is the second most prevalent cancer among women. It can have several causes; an infection with some type of human papillomavirus (HPV) is the greatest risk factor for cervical cancer. Over 100 types of HPVs have been identified, and more than 40 types of HPVs are typically transmitted through sexual contact and infect the anogenital region. Among these, a number of HPVs types, containing types 16 and 18, are classified as "high-risk" HPVs that can cause cervical cancer. The HPVs vaccine prevents infection with certain species of HPVs associated with the development of cervical cancer, genital warts, and some less common cancers. Two HPVs vaccines are currently on the global market: quadrivalent HPVs vaccine and bivalent HPV vaccine that use virus-like particles as a vaccine antigen. This review discusses the current status of HPVs vaccines on the global market, clinical trials, and the future of HPVs vaccine development. PMID:25003090

  16. HPV (Human Papillomavirus) vaccine - what you need to know

    MedlinePlus

    ... taken in its entirety from the CDC HPV (Human Papillomavirus) Vaccine Information Statement (VIS): www.cdc.gov/ ... statements/hpv.html . CDC review information for HPV (Human Papillomavirus) VIS: Page last reviewed: December 2, 2016 ...

  17. Involvement of human papillomavirus infections in prostate cancer progression.

    PubMed

    Al Moustafa, Ala-Eddin

    2008-08-01

    High-risk human papillomaviruses (HPVs) are sexually transmitted and have been associated with several human carcinomas especially cervical and colorectal. On the other hand, a small number of studies have examined the presence of high-risk HPV in human prostate cancer tissues. Currently, the presence and role of high-risk HPV infections in prostate carcinogenesis remain unclear because of the limited number of investigations. This raises the question whether high-risk HPV infections play any role in human prostate cancer development. However, other investigators and our group were able to immortalize normal and cancer prostate epithelial cells in vitro by E6/E7 of HPV type 16. In this paper, we propose the hypothesis that normal and cancer prostate epithelial cells are susceptible to persistent HPV infections; therefore, high-risk HPV infections play an important role in the progression of prostate cancer. We believe that an international collaboration of epidemiological studies and more molecular biology investigations are necessary to answer these important questions.

  18. Up-regulation of 14-3-3sigma (Stratifin) is associated with high-grade CIN and high-risk human papillomavirus (HPV) at baseline but does not predict outcomes of HR-HPV infections or incident CIN in the LAMS study.

    PubMed

    Syrjänen, Stina; Naud, Paulo; Sarian, Luis; Derchain, Sophie; Roteli-Martins, Cecilia; Longatto-Filho, Adhernar; Tatti, Silvio; Branca, Margerita; Erzen, Mojca; Hammes, Luciano S; Costa, Silvano; Syrjänen, Kari

    2010-02-01

    To assess whether the potentially high-risk (HR) human papillomavirus (HPV)-related up-regulation of 14-3-3sigma (stratifin) has implications in the outcome of HPV infections or cervical intraepithelial neoplasia (CIN) lesions, cervical biopsy specimens from 225 women in the Latin American Screening Study were analyzed for 14-3-3sigma expression using immunohistochemical analysis. We assessed its associations with CIN grade and HR HPV at baseline and value in predicting outcomes of HR-HPV infections and the development of incident CIN 1+ and CIN 2+. Expression of 14-3-3sigma increased in parallel with the lesion grade. Up-regulation was also significantly related to HR-HPV detection (P = .004; odds ratio, 2.71; 95% confidence interval, 1.37-5.35) and showed a linear relationship to HR-HPV loads (P = .003). 14-3-3sigma expression was of no value in predicting the outcomes (incident, persistent, clearance) of HR-HPV infections or incident CIN 1+ and CIN 2+. 14-3-3sigma is not inactivated in cervical carcinoma and CIN but is up-regulated on transition from CIN 2 to CIN 3. Its normal functions in controlling G(1)/S and G(2)/M checkpoints are being bypassed by HR HPV.

  19. Role of antibodies to human papillomavirus 16 in prostate cancer: A seroscreening by peptide microarray.

    PubMed

    Zhao, Xiaojun; Zhou, Zheng; Chen, Ye; Chen, Wen; Ma, Hongwei; Pu, Jinxian

    2017-06-01

    Evidence is accumulating in estimating the potential role of human papillomavirus infection in prostate carcinogenesis. However, the results remain inconclusive. We measured the serostatus of antibodies to one of the high-risk human papillomaviruses, human papillomavirus 16, with a newly developed peptide microarray. Serum samples were collected from 75 untreated prostate cancer patients, along with 80 control subjects. We identified 12 peptides with significant differences in prostate cancer samples from all 241 peptides derived from human papillomavirus 16. Our results showed human papillomavirus 16 infection in 64.0% of prostate cancer serum samples, which is significantly different compared with the controls ( p < 0.01) because only 17.5% of the control serum was considered seropositive. The area under the receiver operator characteristic curve was 0.793 (95% confidence interval 0.721-0.864), indicating that the new microarray technique may have diagnostic value. The results showed an association between serological evidence for human papillomavirus 16 infection and risk of prostate cancer. The different serostatus of antibodies in the two subgroups indicated that human papillomavirus 16 infection might occur and play a potential role of progression in a minority of prostate cancer.

  20. Human Papillomavirus and Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Hennessey, P.T.; Westra, W.H.; Califano, J.A.

    2009-01-01

    Over the past 20 years, high-risk human papillomavirus (HPV) infection has been established as a risk factor for developing head and neck squamous cell carcinoma, independent of tobacco and alcohol use. In particular, HPV is strongly associated with the development of oropharyngeal cancer and a small minority of oral cavity cancers. In this review, we summarize what is currently known about the biology of HPV, the mechanisms by which it effects malignant transformation, and the potential impact of HPV status on the clinical management of persons with head and neck cancer. PMID:19407148

  1. Global challenges of implementing human papillomavirus vaccines.

    PubMed

    Graham, Janice E; Mishra, Amrita

    2011-06-30

    Human Papillomavirus vaccines are widely hailed as a sweeping pharmaceutical innovation for the universal benefit of all women. The implementation of the vaccines, however, is far from universal or equitable. Socio-economically marginalized women in emerging and developing, and many advanced economies alike, suffer a disproportionately large burden of cervical cancer. Despite the marketing of Human Papillomavirus vaccines as the solution to cervical cancer, the market authorization (licensing) of the vaccines has not translated into universal equitable access. Vaccine implementation for vulnerable girls and women faces multiple barriers that include high vaccine costs, inadequate delivery infrastructure, and lack of community engagement to generate awareness about cervical cancer and early screening tools. For Human Papillomavirus vaccines to work as a public health solution, the quality-assured delivery of cheaper vaccines must be integrated with strengthened capacity for community-based health education and screening.

  2. Global challenges of implementing human papillomavirus vaccines

    PubMed Central

    2011-01-01

    Human Papillomavirus vaccines are widely hailed as a sweeping pharmaceutical innovation for the universal benefit of all women. The implementation of the vaccines, however, is far from universal or equitable. Socio-economically marginalized women in emerging and developing, and many advanced economies alike, suffer a disproportionately large burden of cervical cancer. Despite the marketing of Human Papillomavirus vaccines as the solution to cervical cancer, the market authorization (licensing) of the vaccines has not translated into universal equitable access. Vaccine implementation for vulnerable girls and women faces multiple barriers that include high vaccine costs, inadequate delivery infrastructure, and lack of community engagement to generate awareness about cervical cancer and early screening tools. For Human Papillomavirus vaccines to work as a public health solution, the quality-assured delivery of cheaper vaccines must be integrated with strengthened capacity for community-based health education and screening. PMID:21718495

  3. The effect of intrauterine devices on acquisition and clearance of human papillomavirus.

    PubMed

    Averbach, Sarah H; Ma, Yifei; Smith-McCune, Karen; Shiboski, Stephen; Moscicki, Anna B

    2017-04-01

    Previous studies have shown a decrease in cervical cancer associated with intrauterine device use. It has been hypothesized that intrauterine device use may alter the natural history of human papillomavirus infections, preempting development of precancerous lesions of the cervix and cervical cancer, but the effect of intrauterine devices on the natural history of human papillomavirus infection and subsequent development of cervical cancer is poorly understood. The purpose of this study was to evaluate the association between intrauterine device use and cervical high-risk human papillomavirus acquisition and clearance. This is a prospective cohort study conducted from October 2000 through June 2014 among 676 sexually active young women and girls enrolled from family planning clinics in San Francisco, CA. Data were analyzed using a Cox proportional hazards model, including time-varying indicators of intrauterine device use, and adjusting for fixed and time-dependent predictor variables. A total of 85 women used an intrauterine device at some time during follow-up. Among 14,513 study visits, women reported intrauterine device use at 505 visits. After adjusting for potential behavioral confounders, there was no association between intrauterine device use and human papillomavirus acquisition (hazard ratio, 0.50; 95% confidence interval, 0.20-1.23; P = .13) or clearance of human papillomavirus infection (hazard ratio, 1.44; 95% confidence interval, 0.76-2.72; P = .26). Current intrauterine device use is not associated with acquisition or persistence of human papillomavirus infection. Intrauterine device use is safe among women and girls with human papillomavirus infections and at risk for human papillomavirus acquisition. Intrauterine device use may play a role further downstream in the natural history of cervical cancer by inhibiting the development of precancerous lesions of the cervix in human papillomavirus-infected women, or enhancing clearance of established

  4. The biology of beta human papillomaviruses.

    PubMed

    Tommasino, Massimo

    2017-03-02

    The beta genus comprises more than 50 beta human papillomavirus (HPV) types that are suspected to be involved, together with ultraviolet (UV) irradiation, in the development of non-melanoma skin cancer (NMSC), the most common form of human cancer. Two members of the genus beta, HPV5 and HPV8, were first identified in patients with a genetic disorder, epidermodysplasia verruciformis (EV), that confers high susceptibility to beta HPV infection and NMSC development. The fact that organ transplant recipients (OTRs) with an impaired immune system have an elevated risk of NMSC raised the hypothesis that beta HPV types may also be involved in skin carcinogenesis in non-EV patients. Epidemiological studies have shown that serological and viral DNA markers are weakly, but significantly, associated with history of NMSC in OTRs and the general population. Functional studies on mucosal high-risk (HR) HPV types have clearly demonstrated that the products of two early genes, E6 and E7, are the main viral oncoproteins, which are able to deregulate events closely linked to transformation, such as cell cycle progression and apoptosis. Studies on a small number of beta HPV types have shown that their E6 and E7 oncoproteins also have the ability to interfere with the regulation of key pathways/events associated with cellular transformation. However, the initial functional data indicate that the molecular mechanisms leading to cellular transformation are different from those of mucosal HR HPV types. Beta HPV types may act only at early stages of carcinogenesis, by potentiating the deleterious effects of other carcinogens, such as UV radiation.

  5. Disclosure of Genital Human Papillomavirus Infection to Female Sex Partners by Young Men

    PubMed Central

    Arima, Yuzo; Winer, Rachel L; Kurth, Ann E; Martin, Diane P; Hughes, James P; Stern, Michael E; Feng, Qinghua; Kiviat, Nancy B; Koutsky, Laura A

    2012-01-01

    A survey was administered to male university students testing positive for high-risk human papillomavirus. Disclosure was more likely in men with fewer partners, in main partnerships, and in longer partnerships. Disclosure was associated with discussing the Pap test/HPV vaccine with female partners and not associated with a worsening relationship. PMID:22797688

  6. Molecular Diagnosis for Nodal Metastasis in Endoscopically Managed Cervical Cancer: The Accuracy of the APTIMA Test to Detect High-risk Human Papillomavirus Messenger RNA in Sentinel Lymph Nodes.

    PubMed

    Köhler, Christhardt; Le, Xin; Dogan, Nasuh Utku; Pfiffer, Tatiana; Schneider, Achim; Marnitz, Simone; Bertolini, Julia; Favero, Giovanni

    2016-01-01

    To evaluate the feasibility and accuracy of a commercially available test to detect E6/E7 mRNA of 14 subtypes of high-risk HPVs (APTIMA; Hologic, Bedford, MA) in the sentinel lymph nodes of CC patients laparoscopically operated. Prospective pilot study. The study was conducted in the Department of Advanced Operative and Oncologic Gynecology, Asklepios Hospital, Hamburg, Germany. 54 women with HPV-positive CC submitted to laparoscopic sentinel node biopsy alone or sentinel node biopsy followed by systematic pelvic and/or para-aortic endoscopic lymphadenectomy. All removed sentinel lymph nodes (SLNs) underwent sample collection by cytobrush for the APTIMA assay before frozen section. Results obtained with the HPV mRNA test were compared with the definitive histopathological analysis of the SLNs and additional lymph nodes removed. A total of 125 SLNs (119 pelvic and 6 paraaortic) were excised with a mean number of 2.3 SLNs per patient. Final histopathologic analysis confirmed nodal metastases in 10 SLNs from 10 different patients (18%). All the histologically confirmed metastatic lymph nodes were also HPV E6/E7 mRNA positive, resulting in a sensitivity of 100%. Four histologically free sentinel nodes were positive for HPV E6/E7 mRNA, resulting in a specificity of 96.4%. The HPV E6/E7 mRNA assay in the SLNs of patients with CC is feasible and highly accurate. The detection of HPV mRNA in 4 women with negative SLNs might denote a shift from microscopic identification of metastasis to the molecular level. The prognostic value of this findings awaits further verification. Copyright © 2016. Published by Elsevier Inc.

  7. Comparison of the Cobas 4800 HPV and HPV 9G DNA Chip Tests for Detection of High-Risk Human Papillomavirus in Cervical Specimens of Women with Consecutive Positive HPV Tests But Negative Pap Smears.

    PubMed

    Jun, Sun-Young; Park, Eun Su; Kim, Jiyoung; Kang, Jun; Lee, Jae Jun; Bae, Yoonjin; Kim, Sang-Il; Maeng, Lee-So

    2015-01-01

    Detecting high-risk (HR) HPV is important for clinical management of women with persistent HPV-positive and Pap-negative results. The Cobas 4800 HPV test is the first FDA-approved HPV DNA test that can be used alone as a first-line screening tool. The HPV 9G DNA chip test is a PCR-based DNA microarray assay. We evaluated the patients of consecutive HPV-positivity on HPV 9G DNA chip test without cytologic abnormalities. We then compared the performances of HPV 9G DNA chip and the Cobas 4800 HPV tests for detecting HR HPV with each other and confirmed HPV genotyping using direct sequencing. All 214 liquid-based cytology specimens were collected from 100 women with consecutive HPV-positive and Pap-negative results on the HPV 9G DNA chip test between May 2012 and Dec 2013, but only 180 specimens were available for comparing HPV test results. The HPV 9G DNA chip and the Cobas 4800 HPV tests agreed with each other in 81.7% of the samples, and the concordance rate was greater than 97.2% for detecting HPV-16 or -18. For HR genotypes other than HPV types 16 and 18, the two tests agreed for 81.1% of the samples. The sensitivity of both assays for detecting HR HPV was 100%, regardless of HR genotypes. The HPV 9G DNA chip test may be as effective as the Cobas 4800 HPV test in detecting HR HPV, and has a similar ability to identify HPV-16 and -18.

  8. Comparison of the Cobas 4800 HPV and HPV 9G DNA Chip Tests for Detection of High-Risk Human Papillomavirus in Cervical Specimens of Women with Consecutive Positive HPV Tests But Negative Pap Smears

    PubMed Central

    Jun, Sun-Young; Park, Eun Su; Kim, Jiyoung; Kang, Jun; Lee, Jae Jun; Bae, Yoonjin; Kim, Sang-Il; Maeng, Lee-So

    2015-01-01

    Detecting high-risk (HR) HPV is important for clinical management of women with persistent HPV-positive and Pap-negative results. The Cobas 4800 HPV test is the first FDA-approved HPV DNA test that can be used alone as a first-line screening tool. The HPV 9G DNA chip test is a PCR-based DNA microarray assay. We evaluated the patients of consecutive HPV-positivity on HPV 9G DNA chip test without cytologic abnormalities. We then compared the performances of HPV 9G DNA chip and the Cobas 4800 HPV tests for detecting HR HPV with each other and confirmed HPV genotyping using direct sequencing. All 214 liquid-based cytology specimens were collected from 100 women with consecutive HPV-positive and Pap-negative results on the HPV 9G DNA chip test between May 2012 and Dec 2013, but only 180 specimens were available for comparing HPV test results. The HPV 9G DNA chip and the Cobas 4800 HPV tests agreed with each other in 81.7% of the samples, and the concordance rate was greater than 97.2% for detecting HPV-16 or -18. For HR genotypes other than HPV types 16 and 18, the two tests agreed for 81.1% of the samples. The sensitivity of both assays for detecting HR HPV was 100%, regardless of HR genotypes. The HPV 9G DNA chip test may be as effective as the Cobas 4800 HPV test in detecting HR HPV, and has a similar ability to identify HPV-16 and -18. PMID:26469982

  9. 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

  10. Human papillomavirus infection in female sex workers in Lima, Peru.

    PubMed

    Montano, Silvia M; Hsieh, Evelyn J; Calderón, Martha; Ton, Thanh G N; Quijano, Eberth; Solari, Vicky; Zunt, Joseph R

    2011-02-01

    To determine the prevalence and risk factors for human papillomavirus (HPV) infection in female sex workers (FSW) in Lima, Peru. Cross-sectional study of 87 FSW. Information regarding demographics, sex work practices, and genital and blood specimens was collected. Forty-four (50.6%) of 87 FSW had HPV detected in cervical swabs. The prevalence of coinfection by two or more HPV types was 39.1%. Thirty-one (35.6%) were infected by at least one high-risk HPV type, representing 70.5% of women with HPV infection. HPV infection was associated with younger age but not with any demographic or sexual characteristics. Our study confirms the high prevalence of HPV infection in FSW reported by other groups and suggests that brothel-based FSW may be at lower risk for acquiring high-risk HPV infection.

  11. Human papillomavirus infection in female sex workers in Lima, Peru

    PubMed Central

    Montano, Silvia M; Hsieh, Evelyn J; Calderón, Martha; Ton, Thanh G N; Quijano, Eberth; Solari, Vicky; Zunt, Joseph R

    2012-01-01

    Objectives To determine the prevalence and risk factors for human papillomavirus (HPV) infection in female sex workers (FSW) in Lima, Peru. Methods Cross-sectional study of 87 FSW. Information regarding demographics, sex work practices, and genital and blood specimens was collected. Results Forty-four (50.6%) of 87 FSW had HPV detected in cervical swabs. The prevalence of coinfection by two or more HPV types was 39.1%. Thirty-one (35.6%) were infected by at least one high-risk HPV type, representing 70.5% of women with HPV infection. HPV infection was associated with younger age but not with any demographic or sexual characteristics. Conclusions Our study confirms the high prevalence of HPV infection in FSW reported by other groups and suggests that brothel-based FSW may be at lower risk for acquiring high-risk HPV infection. PMID:20813720

  12. Genetic alterations by human papillomaviruses in oncogenesis.

    PubMed

    Lazo, P A; Gallego, M I; Ballester, S; Feduchi, E

    1992-03-30

    The integration sites in the cellular genome of human papillomavirus are located in chromosomal regions always associated with oncogenes or other known tumor phenotypes. Two regions, 8q24 and 12q13, are common to several cases of cervical carcinoma and can have integrated more than one type of papillomavirus DNA. These two chromosomal regions contain several genes implicated in oncogenesis. These observations strongly imply that viral integration sites of DNA tumor viruses can be used as the access point to chromosomal regions where genes implicated in the tumor phenotype are located, a situation similar to that of non-transforming retroviruses.

  13. Lichenoid drug eruption after human papillomavirus vaccination.

    PubMed

    Laschinger, Mary E; Schleichert, Rachel A; Green, Brian

    2015-01-01

    Lichenoid drug reactions have been linked to a long and growing list of medications, most of which are used mainly in adults, making these reactions exceedingly rare in children. To the best of our knowledge, this case report is the first of a lichenoid drug eruption in a child after human papillomavirus vaccination.

  14. Four historic legends in human papillomaviruses research.

    PubMed

    Mammas, Ioannis N; Spandidos, Demetrios A

    2015-01-01

    Human papillomaviruses (HPVs) infection and HPVs-associated lesions, including skin warts in children and adults and cervical neoplasia in women, have been excessively studied since ancient years. In our article, we present briefly four major researchers from the HPVs pre-vaccination historic period: Hippokrates the Asclepiad, Domenico Antonio Rigoni-Stern, George N. Papanicolaou and Harald zur Hausen.

  15. Human Papillomavirus: A Catalyst to a Killer

    ERIC Educational Resources Information Center

    Richman, Alice

    2005-01-01

    Genital human papillomavirus (HPV) is the most prevalent and widespread sexually transmitted disease and is responsible for almost all cases of cervical cancer worldwide. However, HPV has received little public health attention, is not a reportable STD, and often is absent from the repertoire of STDs. In addition, there is pervasive misinformation…

  16. [Melanoma and Human Papillomaviruses: Is There an Outlook for Study?].

    PubMed

    Volgareva, G M; Mikhaylova, I N; Golovina, D A

    2016-01-01

    Melanoma is one of the most aggressive human malignant tumors. Its incidence and mortality are growing steadily. Ultraviolet irradiation is the main risk factor for melanoma involved in melanomagenesis. The probability of viral etiology of melanoma has been discussed. Human papillomaviruses (HPV) have been mentioned among candidates for its etiologic agents because some HPV types are the powerful carcinogens causing cervical cancer and other cancers. The review analyses the literature data on the association of melanoma with HPV Several groupsfound HPVin skin melanomas as well as in mucosa; viruses of high oncogenic risk were detected in some cases. For some organs the etiological role of high-risk HPV as inducers of invasive carcinomas is confirmed. These organs require special mention: cervix uteri, vulva, vagina, penis, anal region, and oral cavity. However in the majority of the studies in which viral DNA-positive melanomas were found, testing for viral genome expression was not done while this is the fact of primary importance. HPVare found in normal skin and mucous membranes thus creating justifiable threat of tumor specimen contamination with viral DNA in vivo. There are limited data on aggravation of the disease prognosis in papillomavirus-positive melanomas. However, any systematic observation of a sizeable patient group distinguished by that tumor type has not been performed yet. Viral E6 and E7 oncogenes of high-risk papillomaviruses were shown to be able to transform normal human melanocytes in vitro experiments. Thus, we can assume the presence of the association of melanoma with oncogenic HPV. The clinical significance of this problem is indisputable under the conditions of the steady increase in melanoma incidence and mortality rates in Russia and abroad. The problem requires further study.

  17. Carbonic anhydrase IX (CA-IX) and high-risk human papillomavirus (H-HPV) as diagnostic biomarkers of cervical dysplasia/neoplasia in Japanese women with a cytologic diagnosis of atypical glandular cells (AGC): a Gynecologic Oncology Group (GOG) Study

    PubMed Central

    Liao, S-Y; Rodgers, W H; Kauderer, J; Bonfiglio, T A; Darcy, K M; Carter, R; Levine, L; Spirtos, N M; Susumu, N; Fujiwara, K; Walker, J L; Hatae, M; Stanbridge, E J

    2011-01-01

    Background: High-risk human papillomavirus (H-HPV) infection is linked to cervical neoplasia but its role in detecting cervical glandular lesions (GLs) is unclear. Carbonic anhydrase IX (CA-IX) is a hypoxic biomarker that is highly expressed in neoplastic cervical GLs. The diagnostic utility of these biomarkers was evaluated by the Gynecologic Oncology Group in Japanese women with a cytological diagnosis of atypical glandular cells. Methods: Immunostaining was used to detect CA-IX in a conventional Pap smear. Immunoreactivity of CA-IX was interpreted by a panel of pathologists blinded to the histological diagnosis. Polymerase chain reaction was used to detect H-HPV in a liquid-based cytology specimen. Results: Significant cervical lesions (SCLs), defined as cervical intraepithelial neoplasia (CIN2, CIN3), adenocarcinoma in situ or invasive carcinoma, were observed in 37/88 (42%) of women. CA-IX testing alone (n=88) had a sensitivity of 89, 100 or 73% for SCLs, GLs or significant squamous lesions (SLs), respectively, with a false negative rate (FNR) of 14%. Testing for H-HPV (n=84) had a sensitivity of 65, 53 or 80% for SCLs, GLs or SLs, respectively, with a FNR of 22%. The combination of CA-IX and H-HPV testing had a sensitivity of 97, 100 or 93% for SCLs, GLs or SLs, respectively, with a FNR of 5%. Among eight H-HPV-negative GLs, six (75%) had a diagnosis of lobular endocervical glandular hyperplasia (LEGH). Conclusion: The combination of CA-IX and HPV testing improved the diagnostic accuracy. The low rate of H-HPV positivity in the GLs was associated with coexisting LEGH independent of H-HPV. PMID:21157448

  18. Risk estimates for persistent high-risk human papillomavirus infections as surrogate endpoints of progressive cervical disease critically depend on reference category: analysis of the combined prospective cohort of the New Independent States of the Former Soviet Union and Latin American Screening studies.

    PubMed

    Syrjänen, K; Shabalova, I; Naud, P; Kozachenko, V; Derchain, S; Zakharchenko, S; Roteli-Martins, C; Nerovjna, R; Longatto-Filho, A; Kljukina, L; Tatti, S; Branovskaja, M; Hammes, L S; Branca, M; Grunjberga, V; Eržen, M; Juschenko, A; Costa, S; Sarian, L; Podistov, J; Syrjänen, S

    2011-06-01

    To make feasible future clinical trials with new-generation human papillomavirus (HPV) vaccines, novel virological surrogate endpoints of progressive disease have been proposed, including high-risk HPV (HR-HPV) persistence for six months (6M+) or 12 months (12M+). The risk estimates (relative risks [RRs]) of these 'virological endpoints' are influenced by several variables, not yet validated adequately. We compared the impact of three referent groups: (i) HPV-negative, (ii) HPV-transient, (iii) HPV-mixed outcome on the risk estimates for 6M+ or 12M+ HR-HPV persistence as predictors of progressive disease. Generalized estimating equation models were used to estimate the strength of 6M+ and 12M+ HR-HPV persistence with disease progression to squamous intraepithelial lesions (SILs), cervical intraepithelial neoplasia (CIN) grade 1+, CIN2+, CIN/SIL endpoints, comparing three optional reference categories (i)-(iii) in a prospective sub-cohort of 1865 women from the combined New Independent States of the Former Soviet Union (NIS) and Latin American Screening (LAMS) studies cohort (n = 15,301). The RRs of these viral endpoints as predictors of progressive disease are affected by the length of viral persistence (6M+ or 12M+) and the surrogate endpoint (SIL, CIN1, CIN2, CIN/SIL). Most dramatic is the effect of the referent group used in risk estimates, with the HPV-negative referent group giving the highest and most consistent RRs for both 6M+ and 12M+ viral persistence, irrespective of which surrogate is used. In addition to deciding on whether to use 6M+ or 12M+ persistence criteria, and cytological, histological or combined surrogate endpoints, one should adopt the HPV-negative referent group as the gold standard in all future studies using viral persistence as the surrogate endpoint of progressive disease.

  19. The association of human papillomavirus vaccination with sexual behaviours and human papillomavirus knowledge: a systematic review.

    PubMed

    Coles, Victoria A H; Patel, Ajay S; Allen, Felicity L; Keeping, Sam T; Carroll, Stuart M

    2015-10-01

    Since the 2008 introduction of the human papillomavirus (HPV) vaccination programme for adolescent girls in the UK, parents and other groups have expressed fears that immunisation condones sexual activity, promotes promiscuity and encourages risky sexual behaviour. This study aimed to explore whether HPV vaccination programmes have increased knowledge surrounding HPV and associated disease and whether uptake has influenced sexual behaviour. MEDLINE, Embase, Cochrane Library and PsycINFO electronic databases were interrogated. Studies of behaviour, attitudes and knowledge associated with HPV vaccination (or vaccination intent) in subjects of any age and gender in programmes reflective of UK practice were included in the review (n = 58). The evidence regarding the association of HPV vaccination with high-risk sexual behaviour was varied, primarily due to the heterogeneous nature of the included studies. Young females typically exhibited better knowledge than males, and vaccinated respondents (or those with vaccination intent) had higher levels of knowledge than the unvaccinated. However, knowledge surrounding HPV and genital warts was generally poor. This review highlights the need to provide effective education regarding the HPV vaccine and HPV-associated disease to adolescents of vaccination age, nurses, teachers, parents and guardians to ultimately allow informed decisions to be made regarding receipt of the HPV vaccine.

  20. Human Alpha and Beta Papillomaviruses Use Different Synonymous Codon Profiles

    PubMed Central

    Cladel, Nancy M.; Bertotto, Alex; Christensen, Neil D.

    2013-01-01

    Human papillomaviruses use rare codons relative to their hosts. It has been theorized that this is a mechanism to allow the virus to escape immune surveillance. In the present study we examined the codings of four major genes of 21 human alpha (mucosatropic) viruses and 16 human beta (cutaneous-tropic) viruses. We compared the codon usage of different genes from a given papillomavirus and also the same genes from different papillomaviruses. Our data showed that codon usage was not always uniform between two genes of a given papillomavirus or between the same genes of papillomaviruses from different genera. We speculate as to why this might be and conclude that codon usage in the papillomaviruses may not only play a role in facilitating escape from immune surveillance but may also underlie some of the unanswered questions in the papillomavirus field. PMID:20157772

  1. Human alpha and beta papillomaviruses use different synonymous codon profiles.

    PubMed

    Cladel, Nancy M; Bertotto, Alex; Christensen, Neil D

    2010-06-01

    Human papillomaviruses use rare codons relative to their hosts. It has been theorized that this is a mechanism to allow the virus to escape immune surveillance. In the present study, we examined the codings of four major genes of 21 human alpha (mucosatropic) viruses and 16 human beta (cutaneous-tropic) viruses. We compared the codon usage of different genes from a given papillomavirus and also the same genes from different papillomaviruses. Our data showed that codon usage was not always uniform between two genes of a given papillomavirus or between the same genes of papillomaviruses from different genera. We speculate as to why this might be and conclude that codon usage in the papillomaviruses may not only play a role in facilitating escape from immune surveillance but may also underlie some of the unanswered questions in the papillomavirus field.

  2. Replication and Assembly of Human Papillomaviruses

    PubMed Central

    Conway, M.J.; Meyers, C.

    2009-01-01

    Human papillomaviruses (HPVs) are small dsDNA tumor viruses, which are the etiologic agents of most cervical cancers and are associated with a growing percentage of oropharyngeal cancers. The HPV capsid is non-enveloped, having a T=7 icosahedral symmetry formed via the interaction among 72 pentamers of the major capsid protein, L1. The minor capsid protein L2 associates with L1 pentamers, although it is not known if each L1 pentamer contains a single L2 protein. The HPV life cycle strictly adheres to the host cell differentiation program, and as such, native HPV virions are only produced in vivo or in organotypic “raft” culture. Research producing synthetic papillomavirus particles—such as virus-like particles (VLPs), papillomavirus-based gene transfer vectors, known as pseudovirions (PsV), and papillomavirus genome-containing quasivirions (QV)—has bypassed the need for stratifying and differentiating host tissue in viral assembly and has allowed for the rapid analysis of HPV infectivity pathways, transmission, immunogenicity, and viral structure. PMID:19407149

  3. Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection.

    PubMed

    Qing, Song; Tulake, Wuniqiemu; Ru, Mingfang; Li, Xiaohong; Yuemaier, Reziwanguli; Lidifu, Dilare; Rouzibilali, Aierken; Hasimu, Axiangu; Yang, Yun; Rouziahong, Reziya; Upur, Halmurat; Abudula, Abulizi

    2017-04-01

    It is known that high-risk human papillomavirus infection is the main etiological factor in cervical carcinogenesis. However, human papillomavirus screening is not sufficient for early diagnosis. In this study, we aimed to identify potential biomarkers common to cervical carcinoma and human papillomavirus infection by proteomics for human papillomavirus-based early diagnosis and prognosis. To this end, we collected 76 cases of fresh cervical tissues and 116 cases of paraffin-embedded tissue slices, diagnosed as cervical squamous cell carcinoma, cervical intraepithelial neoplasia II-III, or normal cervix from ethnic Uighur and Han women. Human papillomavirus infection by eight oncogenic human papillomavirus types was detected in tissue DNA samples using a quantitative polymerase chain reaction. The protein profile of cervical specimens from human papillomavirus 16-positive squamous cell carcinoma and human papillomavirus-negative normal controls was analyzed by proteomics and bioinformatics. The expression of candidate proteins was further determined by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. We identified 67 proteins that were differentially expressed in human papillomavirus 16-positive squamous cell carcinoma compared to normal cervix. The quantitative reverse transcriptase-polymerase chain reaction analysis verified the upregulation of ASAH1, PCBP2, DDX5, MCM5, TAGLN2, hnRNPA1, ENO1, TYPH, CYC, and MCM4 in squamous cell carcinoma compared to normal cervix ( p < 0.05). In addition, the transcription of PCBP2, MCM5, hnRNPA1, TYPH, and CYC was also significantly increased in cervical intraepithelial neoplasia II-III compared to normal cervix. Immunohistochemistry staining further confirmed the overexpression of PCBP2, hnRNPA1, ASAH1, and DDX5 in squamous cell carcinoma and cervical intraepithelial neoplasia II-III compared to normal controls ( p < 0.05). Our data suggest that the expression of ASAH1, PCBP2, DDX5

  4. An exploration of human papillomavirus-related cervical cancer prevention experiences among college women: a descriptive qualitative approach.

    PubMed

    Tu, Yu-Ching; Wang, Hsiu-Hung

    2013-12-01

    To enhance understanding of young women's experiences of human papillomavirus-related cervical cancer prevention in Taiwan. High-risk types of human papillomavirus are a key aetiologic factor behind cervical cancer. Recently, human papillomavirus vaccination is considered an effective approach to prevent vaccine-specific typed human papillomavirus-related cervical cancer in women. However, several controversial issues still arise about routine administration of human papillomavirus vaccines, and the literature on young women's protection against human papillomavirus-related cervical cancer is limited. A descriptive qualitative design categorised responses into themes. Sixteen sexually active college women (aged 20-22 years) were recruited via purposive and snow-ball sampling in Southern Taiwan. Every participant underwent an in-depth interview which was audio-recorded and fully transcribed. Analysis of the interview material was inductive and followed a thematic analysis approach. Procedures to confirm confidentiality, credibility and consistency were considered. This article provides an insight into the college women's experiences in the obstacles to and striving towards breakthroughs of human papillomavirus-related cervical cancer prevention. The obstacles include inadequate health literacy, financial difficulty, negative medical experiences and gender myths. The striving towards breakthroughs consists in self-protection and knowledge support. College women experience difficulties with human papillomavirus-related cervical cancer prevention. They desire to have a publicly funded human papillomavirus immunisation programme, friendly medical environments, sufficient knowledge and open-minded society to maintain their health. Such reflection information is helpful to design effective human papillomavirus-related cervical cancer prevention campaigns. Young women do not know how to protect against human papillomavirus infection, although human papillomavirus

  5. Human papillomavirus infection and immunohistochemical p16(INK4a) expression as predictors of outcome in penile squamous cell carcinomas.

    PubMed

    Bezerra, Stephania M; Chaux, Alcides; Ball, Mark W; Faraj, Sheila F; Munari, Enrico; Gonzalez-Roibon, Nilda; Sharma, Rajni; Bivalacqua, Trinity J; Burnett, Arthur L; Netto, George J

    2015-04-01

    Approximately 50% of penile squamous cell carcinomas (SCC) are associated with high-risk human papillomavirus (HR-HPV) infection. We evaluated the correlation of p16(INK4a) expression and HR-HPV with clinicopathological features and outcome in a cohort of patients with penile SCC. Two tissue microarrays were constructed from 53 invasive penile SCC at our hospital. p16(INK4a) expression was assessed by immunohistochemistry (CINtec Kit). High-risk human papillomavirus status was assessed by in situ hybridization (INFORM HPV III family 16 probe B cocktail). High-risk human papillomavirus was detected in 8 cases (15%), and p16(INK4a) overexpression was found in 23 cases (44%). Both markers showed a significant association with histologic subtype (P = .017 and P = .01, respectively) and lymphovascular invasion (P = .015 and P = .015, respectively). Regarding outcome analyses, neither HPV infection nor p16(INK4a) overexpression significantly predicted overall survival or cancer-specific survival using Cox proportional hazards regression model. High-risk human papillomavirus positivity and p16(INK4a) overexpression were significantly associated with histologic subtype and presence of lymphovascular invasion. Human papillomavirus status was not predictive of outcome in our cohort.

  6. Epidemiology of oral human papillomavirus infection

    PubMed Central

    Chung, Christine H.; Bagheri, Ashley; D'Souza, Gypsyamber

    2013-01-01

    Human papillomavirus (HPV) infection is known to cause a subset of oropharyngeal cancers. Data regarding oral HPV infection is limited but emerging. HPV infection of the genital tract has been more thoroughly researched and helps inform our understanding of oral HPV infection. In this article we review current data on HPV prevalence, natural history, mode of acquisition, and risk factors for oral HPV infection. PMID:24080455

  7. Human Papillomavirus in Head and Neck Cancer

    PubMed Central

    Garbuglia, Anna Rosa

    2014-01-01

    Human papillomavirus (HPV) is currently considered to be a major etiologic factor, in addition to tobacco and alcohol, for oropharyngeal cancer (OPC) development. HPV positive OPCs are epidemiologically distinct from HPV negative ones, and are characterized by younger age at onset, male predominance, and strong association with sexual behaviors. HPV16 is the most prevalent types in oral cavity cancer (OCC), moreover the prevalence of beta, and gamma HPV types is higher than that of alpha HPV in oral cavity. PMID:25256828

  8. Roles of Human Papillomaviruses and p16 in Oral Cancer.

    PubMed

    Sritippho, Thanun; Chotjumlong, Pareena; Iamaroon, Anak

    2015-01-01

    Head and neck cancer, including oral cancer, is the sixth most common cancer in humans worldwide. More than 90% of oral cancers are of squamous cell carcinoma type. Recent studies have shown a strong relationship between human papillomavirus (HPV) infection and head and neck cancer, especially oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). Moreover, the incidence of HPV-related OSCC appears to be on the rise while HPV-unrelated OSCC tends to have stabilized in the past decades. p16, a tumor suppressor gene, normally functions as a regulator of the cell cycle. Upon infection with high-risk types of HPV (HR-HPV), particularly types 16, 18, 31, 33, 34, 35, 39, 51, 52, 56, 58, 59, 66, 68, and 70, the expression of p16 is aberrantly overexpressed. Therefore, the expression of p16 is widely used as a surrogate marker for HPV infection in head and neck cancer.

  9. Human papillomaviruses and carcinogenesis: well-established and novel models.

    PubMed

    Viarisio, Daniele; Gissmann, Lutz; Tommasino, Massimo

    2017-08-01

    Human papillomaviruses (HPVs) infect the cutaneous or mucosal epithelia and are classified phylogenetically as genera and species. Persistent infections by the mucosal high-risk (HR) HPV types from genus alpha are associated with cancer development of the genital and upper respiratory tracts. The products of two early genes, E6 and E7, are the major HR HPV oncoproteins, being essential in all steps of the carcinogenic process. Cutaneous beta HPV types are proposed, together with ultraviolet (UV) radiation, to promote non-melanoma skin cancer development. However, in contrast to the HR HPV types, beta HPV types appear to be required only at an early stage of carcinogenesis, facilitating the accumulation of UV-induced DNA mutations. Although findings in experimental models also suggest that beta HPV types and other carcinogens may synergize in the induction of malignancies, these possibilities need to be confirmed in human studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Enhanced transcriptional activation by E2 proteins from the oncogenic human papillomaviruses.

    PubMed Central

    Kovelman, R; Bilter, G K; Glezer, E; Tsou, A Y; Barbosa, M S

    1996-01-01

    A systematic comparison of transcriptional activation by papillomavirus E2 proteins revealed that the E2 proteins from high-risk human papillomaviruses (human papillomavirus type 16 [HPV-16] and HPV-18) are much more active than are the E2 proteins from low-risk HPVs (HPV-6b and HPV-11). Despite the tropism of HPVs for particular epithelial cell types, this difference in transcriptional activation was observed in a number of different epithelial and nonepithelial cells. The enhanced activities of the E2 proteins from high-risk HPVs did not result from higher steady-state levels of protein in vivo, and in vitro DNA-binding assays revealed similar binding properties for these two classes of E2 proteins. These results demonstrate that the E2 proteins from high-risk HPVs have an intrinsically enhanced potential to activate transcription from promoters with E2-responsive elements. We found that there are also substantial differences between the activation properties of the bovine papillomavirus type 1 E2 protein and those of either of the two classes of HPV E2 proteins, especially with regard to requirements for particular configurations of E2 binding sites in the target promoter. Our results indicate that there are at least three distinct functional classes of E2 proteins and that these classes of E2 proteins may perform different roles during the respective viral life cycles. PMID:8892874

  11. Mucosal and cutaneous human papillomaviruses detected in raw sewages.

    PubMed

    La Rosa, Giuseppina; Fratini, Marta; Accardi, Luisa; D'Oro, Graziana; Della Libera, Simonetta; Muscillo, Michele; Di Bonito, Paola

    2013-01-01

    Epitheliotropic viruses can find their way into sewage. The aim of the present study was to investigate the occurrence, distribution, and genetic diversity of Human Papillomaviruses (HPVs) in urban wastewaters. Sewage samples were collected from treatment plants distributed throughout Italy. The DNA extracted from these samples was analyzed by PCR using five PV-specific sets of primers targeting the L1 (GP5/GP6, MY09/MY11, FAP59/64, SKF/SKR) and E1 regions (PM-A/PM-B), according to the protocols previously validated for the detection of mucosal and cutaneous HPV genotypes. PCR products underwent sequencing analysis and the sequences were aligned to reference genomes from the Papillomavirus Episteme database. Phylogenetic analysis was then performed to assess the genetic relationships among the different sequences and between the sequences of the samples and those of the prototype strains. A broad spectrum of sequences related to mucosal and cutaneous HPV types was detected in 81% of the sewage samples analyzed. Surprisingly, sequences related to the anogenital HPV6 and 11 were detected in 19% of the samples, and sequences related to the "high risk" oncogenic HPV16 were identified in two samples. Sequences related to HPV9, HPV20, HPV25, HPV76, HPV80, HPV104, HPV110, HPV111, HPV120 and HPV145 beta Papillomaviruses were detected in 76% of the samples. In addition, similarity searches and phylogenetic analysis of some sequences suggest that they could belong to putative new genotypes of the beta genus. In this study, for the first time, the presence of HPV viruses strongly related to human cancer is reported in sewage samples. Our data increases the knowledge of HPV genomic diversity and suggests that virological analysis of urban sewage can provide key information useful in supporting epidemiological studies.

  12. Humanized birth in high risk pregnancy: barriers and facilitating factors.

    PubMed

    Behruzi, Roxana; Hatem, Marie; Goulet, Lise; Fraser, William; Leduc, Nicole; Misago, Chizuru

    2010-02-01

    The medical model of childbearing assumes that a pregnancy always has the potential to turn into a risky procedure. In order to advocate humanized birth in high risk pregnancy, an important step involves the enlightenment of the professional's preconceptions on humanized birth in such a situation. The goal of this paper is to identify the professionals' perception of the potential obstacles and facilitating factors for the implementation of humanized care in high risk pregnancies. Twenty-one midwives, obstetricians, and health administrator professionals from the clinical and academic fields were interviewed in nine different sites in Japan from June through August 2008. The interviews were audio taped, and transcribed with the participants' consent. Data was subsequently analyzed using content analysis qualitative methods. Professionals concurred with the concept that humanized birth is a changing and promising process, and can often bring normality to the midst of a high obstetric risk situation. No practice guidelines can be theoretically defined for humanized birth in a high risk pregnancy, as there is no conflict between humanized birth and medical intervention in such a situation. Barriers encountered in providing humanized birth in a high risk pregnancy include factors such as: the pressure of being responsible for the safety of the mother and the fetus, lack of the women's active involvement in the decision making process and the heavy burden of responsibility on the physician's shoulders, potential legal issues, and finally, the lack of midwifery authority in providing care at high risk pregnancy. The factors that facilitate humanized birth in a high risk include: the sharing of decision making and other various responsibilities between the physicians and the women; being caring; stress management, and the fact that the evolution of a better relationship and communication between the health professional and the patient will lead to a stress

  13. Human papillomavirus (HPV) genotyping of cutaneous warts in Greek children.

    PubMed

    Giannaki, Maria; Kakourou, Talia; Theodoridou, Maria; Syriopoulou, Vassiliki; Kabouris, Marios; Louizou, Eirini; Chrousos, George

    2013-01-01

    The human papillomavirus (HPV) infects the squamous epithelium of the skin and produces common warts, plantar warts, and flat warts, which occur commonly on the hands, face, and feet. The objective of this study was to determine the presence of HPV in warts in children in order to associate the virus with the disease. Sixty-eight children with clinically diagnosed cutaneous warts were recruited. Skin biopsy samples were examined and DNA was extracted using a commercially available kit. To distinguish between the HPV types, we used a specific pair of primers to amplify the HPV DNA. Polymerase chain reaction amplification of the L1 region was followed by restriction fragment length polymorphism analysis and Luminex xMAP technology. HPV 57 was the predominant type in our study, although the detection of the high-risk HPV type 16 in 33% of our positive samples indicates the presence of mucosal high-risk HPV types in the skin of children. It seems that the newly introduced Luminex assay maximized the discrimination of genotypes even in the case of multiple HPV infections. Or findings also suggest the presence of high-risk HPV types in cutaneous warts. © 2013 Wiley Periodicals, Inc.

  14. Human papillomavirus vaccination in males: the state of the science.

    PubMed

    Barroso, Luis F; Wilkin, Timothy

    2011-04-01

    Human papillomavirus (HPV) is an extremely prevalent sexually transmitted infection that is typically acquired soon after onset of sexual activity. The burden of HPV-related malignant and nonmalignant disease is high in men and women. High-risk or oncogenic types of HPV cause cervical, vaginal, and vulvar cancer in women. These types have also been shown to cause penile cancer in men and a substantial proportion of oropharyngeal and anal malignancy in men and women. Low-risk types of HPV cause anogenital warts. Prevention of penile, anal, and oropharyngeal cancers and anogenital warts represents potential benefits of the HPV vaccine in men. This review focuses on HPV disease in men, existing data on HPV vaccination in men, and various factors associated with the decision to vaccinate boys and young men, as well as the timing of vaccination.

  15. Human papillomavirus and Epstein Barr virus in prostate cancer: Koilocytes indicate potential oncogenic influences of human papillomavirus in prostate cancer.

    PubMed

    Whitaker, Noel J; Glenn, Wendy K; Sahrudin, Arisha; Orde, Matthew M; Delprado, Warick; Lawson, James S

    2013-02-15

    The purpose of this study is to determine if high risk human papillomaviruses (HPV) and Epstein Barr virus (EBV) are both present in the same prostate cancer specimens. We used a range of analytical techniques including in situ polymerase chain reaction (IS-PCR) and standard liquid PCR followed by sequencing of the product to seek to identify HPV and EBV in normal, benign, and malignant prostate tissues. Both HPV type 18 and EBV gene sequences were identified in a high and approximately equal proportion of normal, benign, and prostate cancer specimens. These sequences were located in the nuclei of prostate epithelial cells. HPV associated koilocytes were identified in 24% of prostate cancer specimens. The presence of both HPV and EBV gene sequences in most of the same normal, benign, and malignant prostate specimens is particularly noteworthy because of recent experimental evidence demonstrating that EBV and HPV can collaborate to increase proliferation of cultured cervical cells. Because the presence of EBV and HPV in normal, benign, and malignant prostate tissues appears to be ubiquitous, it is possible that they are harmless. On the other hand HPV type 18 in particular, has high oncogenic potential and may be associated with some prostate cancers. The identification of HPV associated koilocytes in prostate cancer specimens is an indication of HPV infection and potential oncogenic influences of human papillomavirus in prostate cancer. Copyright © 2012 Wiley Periodicals, Inc.

  16. University Students' Knowledge and Attitudes Regarding Cervical Cancer, Human Papillomavirus, and Human Papillomavirus Vaccines in Turkey

    ERIC Educational Resources Information Center

    Koç, Zeliha

    2015-01-01

    Objectives: The current descriptive study aimed to determine university students' knowledge and attitudes regarding cervical cancer, human papillomavirus (HPV), and HPV vaccines in Turkey. Participants: A total of 800 students participated. Methods: This study was carried out between September 1, 2012, and October 30, 2012, in 8 female…

  17. University Students' Knowledge and Attitudes Regarding Cervical Cancer, Human Papillomavirus, and Human Papillomavirus Vaccines in Turkey

    ERIC Educational Resources Information Center

    Koç, Zeliha

    2015-01-01

    Objectives: The current descriptive study aimed to determine university students' knowledge and attitudes regarding cervical cancer, human papillomavirus (HPV), and HPV vaccines in Turkey. Participants: A total of 800 students participated. Methods: This study was carried out between September 1, 2012, and October 30, 2012, in 8 female…

  18. [Transfer factor effectiveness patients with persistent genital human papillomavirus infection].

    PubMed

    Morfin-Maciel, Blanca María; Sotelo-Ortiz, Julieta Margarita

    2012-01-01

    Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Most HPV infections are cleared within two years by the immune system. Only in 5% to 10% of infected women the infection persists determining a high risk of developing cervical intraepithelial neoplasia. The transfer factor (TF) or dialyzable leukocyte extract is an immunomodulator that has been successfully used as an adjuvant in the treatment of intracelular infections such as recurrent herpes virus diseases. One daily dose of transfer factor was given for five days and subsequently each week for five weeks to a group of women with persistent genital papillomavirus infection. We included 13 patients, aged 19 to 45 years, with first intercourse between the ages of 14 to 23, and a mean of three sexual partners in their lifetime. All of them had persistent HPV that had been treated before with local and ablative therapeutic options, including cervical freezing, cervical conization, cauterizing loop, imiquimod and podophyllin. Transfer factor was administered daily for 5 days, and subsequently at 7-day intervals for 5 weeks. We found a clinical significant improvement in the gynaecological evaluation of cervical, vaginal, vulvar and perineal lesions. No recurrences have developed for at least 1 year of follow-up. The use of transfer factor in women with HPV showed resolution of genital lesions, without recurrences for at least one year after the treatment was ended.

  19. Human Papillomavirus Typing in HIV-Positive Women

    PubMed Central

    Hameed, Meera; Fernandes, Helen; Skurnick, Joan; Moore, Dorothy; Kloser, Patricia

    2001-01-01

    Objective: Human papillomavirus (HPV) is the major cause of cervical carcinoma and cervical intraepithelial neoplasia worldwide. Certain HPV types have a strong association with and probably a causative role in the pathogenesis of premalignant cervical lesions. Epidemiologic studies in women infected by the human immunodeficiency virus (HIV) have shown an increased incidence of squamous intraepithelial lesions (SILs), whichwere predominantly high-grade. Six to 30 per cent of women diagnosed with atypical squamous cells of undetermined significance (ASCUS) on a Papanicolaou (Pap) smear harbor SIL in normal screening populations. This study was undertaken to determine the presence of low- and high-risk HPV types in women infected by HIV and to correlate the results to those of the Pap smear. Study design: HPV DNA typing (low- and high-risk) by Digene™ (Digene Corporation, Gathesburg, MD) hybrid capture methodology was performed on cervical swabs from 209 HIV-positive women. The results of HPV typing were correlated with those of the Pap smear in a retrospective analysis. Results: One hundred and one women (48%) tested positive for HPV subtypes by DNA typing by the hybrid capture method. Of these, 64 patients (63%) had Pap smears whichwere read as being normal, having benign cellular changes, or having ASCUS (favor reactive process). Of these, 19 patients tested positive for both high-risk and low-risk subtypes, 32 patients tested positive only for high-risk subtypes, and 13 patients tested positive only for low-risk subtypes. Conclusion: HPV subtyping identifies a significant group of HIV-positive women who are at risk for developing cervical intraepithelial neoplasia, although they may not show significant abnormalities on their Pap smears. PMID:11495559

  20. Evidence of Human Papillomavirus in the Placenta

    PubMed Central

    Weyn, Christine; Thomas, Dominique; Jani, Jacques; Guizani, Meriem; Donner, Cathérine; Van Rysselberge, Michel; Hans, Christine; Bossens, Michel; Englert, Yvon

    2011-01-01

    Human papillomavirus (HPV) is an epitheliotropic virus typically infecting keratinocytes but also possibly epithelial trophoblastic placental cells. In the present study, we set out to investigate whether HPV can be recovered from transabdominally obtained placental cells to avoid any confounding contamination by HPV-infected cervical cells. Thirty-five placental samples from women undergoing transabdominal chorionic villous sampling were analyzed, and we detected HPV-16 and HPV-62 in 2 placentas. This study suggests that HPV infection of the placenta can occur early in pregnancy. The overall clinical implication of these results remains to be elucidated. PMID:21208925

  1. Human Papillomavirus Entry: Hiding in a Bubble.

    PubMed

    DiGiuseppe, Stephen; Bienkowska-Haba, Malgorzata; Sapp, Martin

    2016-09-15

    Incoming human papillomavirus (HPV) utilize vesicular transport to traffic from the plasma membrane to the trans-Golgi network. Following nuclear envelope breakdown during mitosis, the viral DNA associates with condensed chromosomes utilizing spindle microtubules for delivery. Most intriguingly, the viral DNA resides in a transport vesicle until mitosis is completed and the nuclear envelope has reformed. This finding provides support for the transient existence of nuclear membrane-bound vesicles. Due to their transient nature, it also points to the existence of a cell pathway for the disposal of vesicles ending up fortuitously or purposefully in the nucleus. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  2. Human Papillomavirus Entry: Hiding in a Bubble

    PubMed Central

    DiGiuseppe, Stephen; Bienkowska-Haba, Malgorzata

    2016-01-01

    Incoming human papillomavirus (HPV) utilize vesicular transport to traffic from the plasma membrane to the trans-Golgi network. Following nuclear envelope breakdown during mitosis, the viral DNA associates with condensed chromosomes utilizing spindle microtubules for delivery. Most intriguingly, the viral DNA resides in a transport vesicle until mitosis is completed and the nuclear envelope has reformed. This finding provides support for the transient existence of nuclear membrane-bound vesicles. Due to their transient nature, it also points to the existence of a cell pathway for the disposal of vesicles ending up fortuitously or purposefully in the nucleus. PMID:27412595

  3. The human papillomavirus E7 oncoprotein

    SciTech Connect

    McLaughlin-Drubin, Margaret E. Muenger, Karl

    2009-02-20

    The human papillomavirus (HPV) E7 oncoprotein shares functional similarities with such proteins as adenovirus E1A and SV40 large tumor antigen. As one of only two viral proteins always expressed in HPV-associated cancers, E7 plays a central role in both the viral life cycle and carcinogenic transformation. In the HPV viral life cycle, E7 disrupts the intimate association between cellular differentiation and proliferation in normal epithelium, allowing for viral replication in cells that would no longer be in the dividing population. This function is directly reflected in the transforming activities of E7, including tumor initiation and induction of genomic instability.

  4. Human Papillomavirus: What Every Provider Should Know

    PubMed Central

    Erickson, Britt K.; Alvarez, Ronald D.; Huh, Warner K.

    2012-01-01

    Persistence of Human Papillomavirus (HPV) infection is necessary for the development of cervical cancer. Additionally, infection with HPV is implicated in the majority of cases of other genital tract malignancies including vulvar, penile, and vaginal cancer. HPV testing and vaccination are a routine part of OB/GYN clinical practice. With an enhanced public awareness of HPV infections, many patients turn to their OB/GYN with questions about transmission, testing and prevention. In this review, we will discuss the biology of HPV, epidemiology of disease, methods and indications for testing, and vaccination strategies. PMID:23021131

  5. [Infection therapeutic modalities in human papillomavirus].

    PubMed

    Carrillo Pacheco, Adia; Hernández Valencia, Marcelino; Hernández Quijano, Tomás; Zárate, Arturo

    2012-11-01

    Human papillomavirus (HPV) genital it can infect any mucous of the body and to cause cancer of the uterine cervix. Until recently specific treatments did not exist on this infection, for what had to destroy or to remove the injured tissue by diverse procedures, what could have obstetric repercussions in young women. Recently some surgical modalities and topical drugs have arisen, as well as of systemic employment that allow to arrive to the lesions difficult to approach, and have demonstrated good effectiveness to cure the infection for HPV, for what an analysis of the medical treatment of this infection type is made.

  6. Human papillomavirus genotyping and integration in ovarian cancer Saudi patients

    PubMed Central

    2013-01-01

    Background Human papillomavirus (HPV) is associated with different malignancies but its role in the pathogenesis of ovarian cancer is controversial. This study investigated the prevalence, genotyping and physical state of HPV in ovarian cancer Saudi patients. Methods Hundred formalin fixed paraffin embedded (FFPE) ovarian carcinoma tissues and their normal adjacent tissues (NAT) were included in the study. HPV was detected by nested polymerase chain reaction (PCR) using degenerated HPVL1 consensus primer pairs MY09/MY11 and GP5+/GP6 + to amplify a broad spectrum of HPV genotypes in a single reaction. The HPV positive samples were further genotyped using DNA sequencing. The physical state of the virus was identified using Amplification of Papillomavirus Oncogene Transcripts (APOT) assay in the samples positive for HPV16 and/or HPV18. Results High percentage of HPV (42%) was observed in ovarian carcinoma compared to 8% in the NAT. The high-risk HPV types 16, 18 and 45 were highly associated with the advanced stages of tumor, while low-risk types 6 and 11 were present in NAT. In malignant tissues, HPV-16 was the most predominant genotype followed by HPV-18 and -45. The percentage of viral integration into the host genome was significantly high (61.1%) compared to 38.9% episomal in HPV positive tumors tissues. In HPV18 genotype the percentage of viral integration was 54.5% compared to 45.5% episomal. Conclusion The high risk HPV genotypes in ovarian cancer may indicate its role in ovarian carcinogenesis. The HPV vaccination is highly recommended to reduce this type of cancer. PMID:24252426

  7. The role of human papillomavirus infection in prostate carcinoma.

    PubMed

    Aghakhani, Arezoo; Hamkar, Rasool; Parvin, Mahmoud; Ghavami, Nastaran; Nadri, Mahsa; Pakfetrat, Attesa; Banifazl, Mohammad; Eslamifar, Ali; Izadi, Nabiollah; Jam, Sara; Ramezani, Amitis

    2011-01-01

    Human papillomavirus (HPV) infections are associated with benign and malignant lesions of the female and male anogenital tract. Currently the possible role of HPV infections in prostate carcinogenesis is a subject of great controversy. In this study we aimed to investigate the role of HPV infection in prostate carcinoma (PCa). The study included formalin-fixed paraffin-embedded tissue samples of 104 primary prostate adenocarcinoma cases and 104 control tissues of benign prostatic hyperplasia (BPH). HPV-DNA was purified and amplified through MY09/MY11 and GP5(+)/GP6(+) primers and subsequently subjected to sequencing. HPV-DNA was found in 13 of 104 (12.5%) PCa and 8 of 104 (7.7%) BPH samples. High-risk HPVs were detected in 10 of 13 (76.9%) PCa and 5 of 8 (62.5%) BPH samples with positive HPV-DNA. Low-risk HPVs were detected in 3 of 13 (23.1%) PCa and 3 of 8 (37.5%) BPH specimens with positive HPV-DNA. There was no significant difference between PCa and BPH specimens regarding HPV-DNA presence or the detection of high-risk and low-risk types of HPV. Our data do not support the role of HPV infection in prostate carcinoma. Further studies are required to elucidate the role of HPV infection in human prostate carcinogenesis.

  8. Gnathic and peripheral ameloblastomas lack human papillomavirus DNA.

    PubMed

    Verduin, Lindsey; Bishop, Justin; Mills, Stacey E

    2015-10-01

    Human papillomavirus (HPV) has been associated with a variety of head and neck neoplasms, including squamous cell carcinomas and Schneiderian papillomas. Ameloblastomas can arise from either the gnathic bones or peripheral soft tissues. Peripheral sinonasal ameloblastomas share clinical features with Schneiderian papillomas. A small number of reports have described detection of HPV DNA within ameloblastomas. However, Most of these cases was reported in the 1990s, used the polymerase chain reaction technique, and only examined gnathic tumors. The current study was designed to determine whether low- or high-risk HPV DNA could be detected in gnathic or peripheral ameloblastomas using in situ hybridization. Twenty-nine examples of gnathic osseous and peripheral head and neck ameloblastomas were obtained from the authors' archives (University of Virginia and the Johns Hopkins Hospital). High-risk HPV DNA was not detected in any of the 29 tumors analyzed. Low-risk HPV DNA was identified in only 1 tumor, which was peripheral in origin, and from an immunocompromised patient. We believe that the HPV in this case represents a background "passenger" infection. This study demonstrates that HPV of either high- or low-risk subtypes is unlikely to play a role in the pathogenesis of sinonasal ameloblastomas. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. A review of methods for detect human Papillomavirus infection

    PubMed Central

    2012-01-01

    Human Papillomavirus (HPV) is the most common sexually transmitted virus. Worldwide, the most common high-risk (HR)-HPV are -16/18, and approximately 70% of cervical cancers (CC) are due to infection by these genotypes. Persistent infection by HR-HPV is a necessary but not sufficient cause of this cancer, which develops over a long period through precursor lesions, which can be detected by cytological screening. Although this screening has decreased the incidence of CC, HPV-related cervical disease, including premalignant and malignant lesions, continues to be a major burden on health-care systems. Although not completely elucidated, the HPV-driven molecular mechanisms underlying the development of cervical lesions have provided a number of potential biomarkers for both diagnostic and prognostic use in the clinical management of women with HPV-related cervical disease, and these biomarkers can also be used to increase the positive predictive value of current screening methods. In addition, they can provide insights into the biology of HPV-induced cancer and thus lead to the development of nonsurgical therapies. Considering the importance of detecting HPV and related biomarkers, a variety of methods are being developed for these purposes. This review summarizes current knowledge of detection methods for HPV, and related biomarkers that can be used to discriminate lesions with a high risk of progression to CC. PMID:23131123

  10. Human papillomavirus genotypes and cervical cancer in northeast Thailand.

    PubMed

    Natphopsuk, Sitakan; Settheetham-Ishida, Wannapa; Pientong, Chamsai; Sinawat, Supat; Yuenyao, Pissamai; Ishida, Takafumi; Settheetham, Dariwan

    2013-01-01

    Human papillomavirus (HPV) is a major cause of cervical cancer. More than 100 HPV genotypes have been identified; however the distribution varies geographically and according to ethnicity. The purpose of this study was to investigate the prevalence and distribution of HPV subtypes among Northeast Thai women. Subjects included 198 cases of SCCA and 198 age-matched, healthy controls. HPV-DNA was amplified by PCR using the consensus primers GP5+/6+ system followed by reverse line blot hybridization genotyping. The prevalence of high-risk HPV infection was 21 (10.1%) and 152 (76.8%) in the controls and in the cases, respectively. High-risk HPV significantly increased the risk for cervical cancer with an OR of 42.4 (95%CI: 22.4-81.4, p<0.001) and an adjusted OR of 40.7-fold (95%CI: 21.5-76.8, p <0.001). HPV-16 was the most prevalent HPV type in the SCCA (56.2%) followed by HPV-58 (17.8%) and HPV-18 (13.6%); whereas HPV-58 (46.4%) was a prominent genotype in the controls followed by HPV-16 (39.3%) and unidentified HPV types (25.0%). These findings indicate that HPV infection remains a critical risk factor for SCCA; particularly, HPV-16, HPV-58 and HPV-18. In order to eradicate cervical cancer, sustained health education, promoted use of prophylactics and a HPV-58 vaccine should be introduced in this region.

  11. Partner Human Papillomavirus Viral Load and Incident Human Papillomavirus Detection in Heterosexual Couples.

    PubMed

    Grabowski, Mary K; Kong, Xiangrong; Gray, Ronald H; Serwadda, David; Kigozi, Godfrey; Gravitt, Patti E; Nalugoda, Fred; Reynolds, Steven J; Wawer, Maria J; Redd, Andrew D; Watya, Stephen; Quinn, Thomas C; Tobian, Aaron A R

    2016-03-15

    The association between partner human papillomavirus (HPV) viral load and incident HPV detection in heterosexual couples is unknown. HPV genotypes were detected in 632 human immunodeficiency virus (HIV)-negative couples followed for 2 years in a male circumcision trial in Rakai, Uganda, using the Roche HPV Linear Array. This assay detects 37 genotypes and provides a semiquantitative measure of viral load based on the intensity (graded 1-4) of the genotype-specific band; a band intensity of 1 indicates a low genotype-specific HPV load, whereas an intensity of 4 indicates a high load. Using Poisson regression with generalized estimating equations, we measured the association between partner's genotype-specific viral load and detection of that genotype in the HPV-discordant partner 1 year later. Incident detection of HPV genotypes was 10.6% among men (54 of 508 genotype-specific visit intervals) and 9.0% among women (55 of 611 genotype-specific visit intervals). Use of male partners with a baseline genotype-specific band intensity of 1 as a reference yielded adjusted relative risks (aRRs) of 1.14 (95% confidence interval [CI], .58-2.27]) for incident detection of that genotype among women whose male partner had a baseline band intensity of 2, 1.75 (95% CI, .97-3.17) among those whose partner had an intensity of 3, and 2.52 (95% CI, 1.40-4.54) among those whose partner had an intensity of 4. Use of female partners with a baseline genotype-specific band intensity of 1 as a reference yielded an aRR of 2.83 (95% CI, 1.50-5.33) for incident detection of that genotype among men whose female partner had a baseline band intensity of 4. These associations were similar for high-risk and low-risk genotypes. Male circumcision also was associated with significant reductions in incident HPV detection in men (aRR, 0.53 [95% CI, .30-.95]) and women (aRR, 0.42 [95% CI, .23-.76]). In heterosexual couples, the genotype-specific HPV load in one partner is associated with the risk of new

  12. Monitoring and ordering practices for human papillomavirus in cervical cytology: findings from the College of American Pathologists Gynecologic Cytopathology Quality Consensus Conference working group 5.

    PubMed

    Booth, Christine N; Bashleben, Christine; Filomena, Carol A; Means, Marilee M; Wasserman, Patricia G; Souers, Rhona J; Henry, Michael R

    2013-02-01

    The association of certain types of human papillomavirus with cervical carcinoma is well established. Human papillomavirus testing is now routinely used to screen for cervical carcinoma and precursor lesions of the cervix (cotesting and reflex testing) and these results are considered in patient triage and management. To provide information about current laboratory practices in human papillomavirus testing and consensus best practice statements based on results from the College of American Pathologists' laboratory-based survey funded by the Centers for Disease Control and Prevention. The College of American Pathologists submitted a paper-based survey to 1245 laboratories in the United States. After review of the initial results, follow-up Web-based survey results, and a literature review by an expert working group, consensus best practice statements were constructed by working group members for presentation at a national consensus conference. These best practice statements were discussed and then voted upon by conference participants. A total of 525 laboratories responded to survey questions about human papillomavirus ordering and monitoring practices, whereas 546 responded to the overall survey. In most laboratories (87.6%), the high-risk human papillomavirus test is ordered as a reflex test by providers. A minority of laboratories (11.9%) routinely bundle low- and high-risk human papillomavirus tests. Most laboratories (84.4%) do not limit testing in patients with atypical squamous cells to women older than 20 years. More than half of laboratories (53.3%) monitor human papillomavirus positive rates in Papanicolaou tests with atypical squamous cells of undetermined significance. It is not appropriate for laboratories to offer low-risk human papillomavirus testing for any clinical circumstance in gynecologic cytology. Laboratories should not order human papillomavirus testing to resolve diagnostic discrepancies. It is a valuable broad measure of laboratory quality

  13. The biology and life-cycle of human papillomaviruses.

    PubMed

    Doorbar, John; Quint, Wim; Banks, Lawrence; Bravo, Ignacio G; Stoler, Mark; Broker, Tom R; Stanley, Margaret A

    2012-11-20

    Human papillomaviruses (HPVs) comprise a diverse group, and have different epithelial tropisms and life-cycle strategies. Many HPVs are classified as low-risk, as they are only very rarely associated with neoplasia or cancer in the general population. These HPVs typically cause inapparent/inconspicuous infections, or benign papillomas, which can persist for months or years, but which are eventually resolved by the host's immune system. Low-risk HPVs are difficult to manage in immunosuppressed people and in individuals with genetic predispositions, and can give rise to papillomatosis, and in rare instances, to cancer. The high-risk HPV types are, by contrast, a cause of several important human cancers, including almost all cases of cervical cancer, a large proportion of other anogenital cancers and a growing number of head and neck tumours. The high-risk HPV types constitute a subset of the genus Alphapapillomavirus that are prevalent in the general population, and in most individuals cause only inconspicuous oral and genital lesions. Cancer progression is associated with persistent high-risk HPV infection and with deregulated viral gene expression, which leads to excessive cell proliferation, deficient DNA repair, and the accumulation of genetic damage in the infected cell. Although their life-cycle organisation is broadly similar to that of the low-risk HPV types, the two groups differ significantly in their capacity to drive cell cycle entry and cell proliferation in the basal/parabasal cell layers. This is thought to be linked, at least in part, to different abilities of the high- and low-risk E6 proteins to modulate the activity of p53 and PDZ-domain proteins, and the differential ability of the E7 proteins to target the several different members of the retinoblastoma protein family. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. Crown Copyright

  14. Human papillomavirus types and recurrent cervical warts

    SciTech Connect

    Nuovo, G.J. ); Pedemonte, B.M. )

    1990-03-02

    The authors analyzed cervical intraepithelial neoplasias (CINs) detected after cryotherapy to determine if recurrence is associated with the same human papillomavirus (HPV) type found in the original lesion. Eight women had detectable HPV DNA in CINs that occurred after ablation of another CIN, and for each patient the HPV type in the pretreatment lesion was different from that in the CIN that appeared after cryotherapy. This compares with 12 women who had HPV detected in two or more CINs present at the same time, 11 of whom had the same HPv type noted. they concluded that although multiple, simultaneous CINs in a woman often contain the same HPV type, recurrent CINs that occur after cryotherapy contain an HPV type different from that present in the pretreatment lesion.

  15. Improving Human Papillomavirus Vaccinations in Military Women.

    PubMed

    Wedel, Sarah; Navarrete, Rebecca; Burkard, Joseph F; Clark, Mary Jo

    2016-10-01

    The purpose of this evidence-based project was to provide patient education to increase human papillomavirus (HPV) vaccination rates in military women. Despite the availability of a vaccine, HPV continues to be the most common sexually transmitted infection in the United States. The goal of this program was to increase patient knowledge and HPV vaccination rates by providing education and a verbal recommendation for vaccination during regularly scheduled well-woman exams. The project resulted in a 65% increase in vaccination rates, raising the preprogram vaccination rate of 55% to a postintervention vaccine percentage of 91%. The results demonstrate the importance of patient education and provider recommendation in vaccine acceptance. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

  16. Human papillomavirus oncoproteins and apoptosis (Review)

    PubMed Central

    JIANG, PEIYUE; YUE, YING

    2014-01-01

    The aim of this study was to review the literature and identify the association between human papillomavirus (HPV) oncoproteins and apoptosis. HPV-associated apoptosis may be primarily blocked by a number of oncoproteins, including E5, E6 and E7. E5 protein protects cells from tumor necrosis factor-associated apoptosis; the oncoprotein E6 predominantly inhibits apoptosis through the p53 pathway; and oncoprotein E7 is involved in apoptosis activation and inhibition. In addition, HPV oncoproteins are involved in activating or repressing the transcription of E6/E7. In conclusion, HPV oncoproteins, including E5, E6 and E7 protein, may interfere with apoptosis via certain regulatory principles. PMID:24348754

  17. Oral contraceptives, human papillomavirus and cervical cancer.

    PubMed

    La Vecchia, Carlo; Boccia, Stefania

    2014-03-01

    Oncogenic human papillomavirus is the key determinant of cervical cancer, but other risk factors interact with it to define individual risk. Among these, there is oral contraceptive (OC) use. A quantitative review of the link between OCs and cervical cancer was performed. Long-term (>5 year) current or recent OC use has been related to an about two-fold excess risk of cervical cancer. Such an excess risk, however, levels off after stopping use, and approaches unity 10 or more years after stopping. The public health implications of OC use for cervical cancer are limited. In any case, such implications are greater in middle-income and low-income countries, as well as in central and eastern Europe and Latin America, where cervical cancer screening and control remain inadequate.

  18. Duty to Advocate: Human Papillomavirus Vaccination

    PubMed Central

    Nichols, Kristen; Girotto, Jennifer; Steele, Amy Mitchell-Van; Stoffella, Sylvia

    2017-01-01

    Despite the excellent benefit-to-risk ratio for human papillomavirus (HPV) vaccination and recommendations for its routine use from the Advisory Committee on Immunization Practices (ACIP), significant controversy surrounding HPV vaccination continues to exist. In light of this controversy and continued low rates of vaccination among U.S. adolescents, the Pediatric Pharmacy Advocacy Group (PPAG) endorses the safety and efficacy of HPV vaccination and agrees with ACIP recommendations for protection of the U.S. population against the potentially severe consequences of HPV. The PPAG recommends that all eligible individuals undergo vaccination. We further recommend that pediatric pharmacists participate in the education of patients and their families and serve as advocates for HPV vaccination. This document serves as an update to the 2008 PPAG position statement.1 PMID:28337085

  19. Human papillomavirus and gastrointestinal cancer: A review

    PubMed Central

    Bucchi, Dania; Stracci, Fabrizio; Buonora, Nicola; Masanotti, Giuseppe

    2016-01-01

    Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Exposure to HPV is very common, and an estimated 65%-100% of sexually active adults are exposed to HPV in their lifetime. The majority of HPV infections are asymptomatic, but there is a 10% chance that individuals will develop a persistent infection and have an increased risk of developing a carcinoma. The International Agency for Research on Cancer has found that the following cancer sites have a strong causal relationship with HPV: cervix uteri, penis, vulva, vagina, anus and oropharynx, including the base of the tongue and the tonsils. However, studies of the aetiological role of HPV in colorectal and esophageal malignancies have conflicting results. The aim of this review was to organize recent evidence and issues about the association between HPV infection and gastrointestinal tumours with a focus on esophageal, colorectal and anal cancers. The ultimate goal was to highlight possible implications for prognosis and prevention. PMID:27672265

  20. Therapy of cutaneous human Papillomavirus infections.

    PubMed

    Rivera, Allison; Tyring, Stephen K

    2004-01-01

    Human Papillomaviruses (HPV) are double-stranded DNA viruses, which result in a variety of clinical manifestations according to type. The most common cutaneous lesions include warts located on the skin and genitalia. Because there is currently no cure for HPV infection, treatment focuses on the alleviation of signs and symptoms. Unfortunately, therapy has not been proved to affect transmissibility. Traditional treatment modalities have focused on the destruction of infected tissue through a variety of techniques. These include podophyllin resin, podophyllotoxin, salicylic acid, trichloroacetic acid, bichloroacetic acid, cryotherapy, laser, and surgical techniques. None of these modalities have been proved to be superior. More recently, immunomodulatory compounds with antiviral properties have demonstrated superior efficacy with clearance rates up to 77% and low recurrence rates. Most importantly, clinical trials of vaccines to prevent acquisition of oncogenic HPV are demonstrating marked safety and efficacy.

  1. New treatments for human papillomavirus infection.

    PubMed

    Muñoz-Santos, C; Pigem, R; Alsina, M

    2013-12-01

    Human papillomavirus infection is very common. In this article, we review the latest developments in the treatment of lesions caused by this virus, with a particular focus on anogenital warts. Sinecatechins and new imiquimod formulations are among the most significant new developments. Others include photodynamic therapy and intralesional immunotherapy, but there is insufficient evidence to recommend their routine use. Finally, while therapeutic vaccines and inhibitory molecules appear to hold great promise, they are still in the early phases of investigation. More studies are needed, and these should have similar designs, larger samples, and sufficiently long follow-up periods to enable the direct comparison of the short-term and long-term effectiveness of different treatment options. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  2. Duty to Advocate: Human Papillomavirus Vaccination.

    PubMed

    Nichols, Kristen; Girotto, Jennifer; Steele, Amy Mitchell-Van; Stoffella, Sylvia

    2017-01-01

    Despite the excellent benefit-to-risk ratio for human papillomavirus (HPV) vaccination and recommendations for its routine use from the Advisory Committee on Immunization Practices (ACIP), significant controversy surrounding HPV vaccination continues to exist. In light of this controversy and continued low rates of vaccination among U.S. adolescents, the Pediatric Pharmacy Advocacy Group (PPAG) endorses the safety and efficacy of HPV vaccination and agrees with ACIP recommendations for protection of the U.S. population against the potentially severe consequences of HPV. The PPAG recommends that all eligible individuals undergo vaccination. We further recommend that pediatric pharmacists participate in the education of patients and their families and serve as advocates for HPV vaccination. This document serves as an update to the 2008 PPAG position statement.1.

  3. Systematic review of human papillomavirus vaccine coadministration.

    PubMed

    Noronha, Alinea S; Markowitz, Lauri E; Dunne, Eileen F

    2014-05-13

    Human papillomavirus (HPV) vaccination is recommended in early adolescence, at an age when other vaccines are also recommended. Administration of multiple vaccines during one visit is an opportunity to improve uptake of adolescent vaccines. We conducted a systematic review of safety and immunogenicity of HPV vaccines coadministered with other vaccines. Our review included 9 studies, 4 of quadrivalent HPV vaccine and 5 of bivalent HPV vaccine; coadministered vaccines included: meningococcal conjugate, hepatitis A, hepatitis B, combined hepatitis A and B, tetanus, diphtheria, acellular pertussis, and inactivated poliovirus vaccines. Studies varied in methods of data collection and measurement of immunogenicity and safety. Noninferiority of immune response and an acceptable safety profile were demonstrated when HPV vaccine was coadministered with other vaccines.

  4. Human papillomavirus molecular biology and disease association

    PubMed Central

    Egawa, Nagayasu; Griffin, Heather; Kranjec, Christian; Murakami, Isao

    2015-01-01

    Summary Human papillomaviruses (HPVs) have evolved over millions of years to propagate themselves in a range of different animal species including humans. Viruses that have co‐evolved slowly in this way typically cause chronic inapparent infections, with virion production in the absence of apparent disease. This is the case for many Beta and Gamma HPV types. The Alpha papillomavirus types have however evolved immunoevasion strategies that allow them to cause persistent visible papillomas. These viruses activate the cell cycle as the infected epithelial cell differentiates in order to create a replication competent environment that allows viral genome amplification and packaging into infectious particles. This is mediated by the viral E6, E7, and E5 proteins. High‐risk E6 and E7 proteins differ from their low‐risk counterparts however in being able to drive cell cycle entry in the upper epithelial layers and also to stimulate cell proliferation in the basal and parabasal layers. Deregulated expression of these cell cycle regulators underlies neoplasia and the eventual progression to cancer in individuals who cannot resolve high‐risk HPV infection. Most work to date has focused on the study of high‐risk HPV types such as HPV 16 and 18, which has led to an understanding of the molecular pathways subverted by these viruses. Such approaches will lead to the development of better strategies for disease treatment, including targeted antivirals and immunotherapeutics. Priorities are now focused toward understanding HPV neoplasias at sites other than the cervix (e.g. tonsils, other transformation zones) and toward understanding the mechanisms by which low‐risk HPV types can sometimes give rise to papillomatosis and under certain situations even cancers. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25752814

  5. Accuracy of urinary human papillomavirus testing for the presence of cervical human papillomaviruses and higher grades of cervical intraepithelial neoplasia.

    PubMed

    Piyathilake, Chandrika J; Badiga, Suguna; Chambers, Michelle M; Brill, Ilene K; Matthews, Roland; Partridge, Edward E

    2016-09-15

    Although urine-based testing for human papillomavirus (HPV) is being explored as a practical approach for cervical cancer screening, whether the results differ by age, race, or indicators of excess body weight or in populations exposed to HPV vaccines has not been documented by previous studies. The purpose of this study was to determine the accuracy of urinary HPV testing for the presence of cervical HPVs and high-grade cervical intraepithelial lesions (grade 2 and 3 cervical intraepithelial neoplasia [CIN]) by the aforementioned population characteristics. The study population consisted of 502 women diagnosed with different grades of CIN. HPV testing was performed with paired urine and cervical cell DNA with the Roche Diagnostics Linear Array test. Agreement coefficient 1 and probabilities were calculated to determine the accuracy of urinary HPV testing for the presence of cervical HPVs and CIN lesions. Substantial to almost perfect agreement (0.66-0.83) was observed in the detection of any HPV genotype in urine specimens versus cervical specimens, regardless of the population characteristics. Although the positive predictive value for the detection of CIN lesions was relatively low, the negative predictive value for CIN-3 was high (≥90%) among women positive for any of the urinary or cervical high-risk human papillomavirus (HR-HPV) genotypes or HPV genotypes not included in currently available HPV vaccines. The results demonstrate that urinary HPV testing provides highly satisfactory results for excluding the possibility of any cervical HPV infections, including HPV types not included in vaccines and CIN lesions associated with any HR-HPV, regardless of a woman's age, race, or excess body weight. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2836-2844. © 2016 American Cancer Society. © 2016 American Cancer Society.

  6. Prognostic value of p16 expression irrespective of human papillomavirus status in patients with oropharyngeal carcinoma.

    PubMed

    Saito, Yuki; Yoshida, Masafumi; Omura, Go; Kobayashi, Kenya; Fujimoto, Chisato; Ando, Mizuo; Sakamoto, Takashi; Asakage, Takahiro; Yamasoba, Tatsuya

    2015-09-01

    In a previous study, we reported the value of p16 expression and alcohol consumption in oropharyngeal carcinoma in Japan. We now report the clinical significance of human papillomavirus status and p16 expression in oropharyngeal carcinoma in Japan. Over a 9-year period, a retrospective case comparison study of the pathology database was conducted at the University of Tokyo to identify tumor samples of oropharyngeal carcinoma. We performed immunohistochemistry for the p16 protein, in situ hybridization for human papillomavirus-deoxyribonucleic acid and polymerase chain reaction for the human papillomavirus-deoxyribonucleic acid oncogene E6 in oropharyngeal carcinoma in Japanese patients. We evaluated the human papillomavirus status in patients with oropharyngeal carcinoma to determine its prevalence and association with prognosis. We defined human papillomavirus(+) and human papillomavirus(-) oropharyngeal carcinoma cohorts as those with and without polymerase chain reaction for the human papillomavirus-deoxyribonucleic acid oncogene E6 or in situ hybridization-human papillomavirus. In oropharyngeal carcinoma, the prevalences of p16(+)human papillomavirus(+), p16(+)human papillomavirus(-), p16(-)human papillomavirus(+) and p16(-)human papillomavirus(-) were 32% (48/150), 7% (10/150), 2% (3/150) and 59% (89/150), respectively. Low tobacco and alcohol consumption, tonsil or base of tongue localization, but not age, were associated with p16(+)human papillomavirus(+). Low alcohol consumption was associated with p16(+)human papillomavirus(-). There was a significant difference in overall survival between p16(+)human papillomavirus(-) and p16(-)human papillomavirus(-) (P = 0.03). In multivariate Cox regression models, p16 was the independent prognostic factor, regardless of human papillomavirus status. p16 expression was a reliable prognostic biomarker regardless of human papillomavirus status. © The Author 2015. Published by Oxford University Press. All rights reserved

  7. Site of infections associated with human papillomavirus.

    PubMed

    Beltrão, Monique; Wanderley, Marcela Silvestre Outtes; de Santana, Nataly Amorim; Bruneska, Danyelly; de Lima Filho, José Luiz

    2015-03-01

    Human papillomavirus (HPV) is the most clinically common sexually transmitted infection due to its carcinogenic power and the high number of lesions that it causes at different sites of the human body. Genital tract organs are the most common sites where the virus can be found, but by increasing the sensitivity of diagnostic technique, it is possible to identify viral presence in different regions of the body such as the stomach, the lung, and the urinary tract. These findings break with the traditional HPV skin/genital tropic profile and demonstrate that the virus is capable of infecting a wide variety of cells, tissues, and organs or can, at least, survive in these areas. The widespread presence of the HPV in the human body, often in latent form, led us to consider the hypothesis that HPV latency may be associated with no disease. This observation raises further questions about the possibility of the virus not causing disease in specific sites of the human body, but rather, behaving like a commensal/opportunistic microorganism.

  8. Negative emotions and stigma associated with a human papillomavirus test result: A comparison between human papillomavirus-positive men and women.

    PubMed

    Daley, Ellen M; Vamos, Cheryl A; Wheldon, Christopher W; Kolar, Stephanie K; Baker, Elizabeth A

    2015-08-01

    Human papillomavirus has largely been framed as a women's health issue, and the psychosocial impact of human papillomavirus among men remains unclear. In this study, we found that women infected with human papillomavirus (n = 154) experienced a greater degree of negative emotions and stigma than human papillomavirus-infected men (n = 190). Among women, younger age and less education were associated with greater expression of negative emotions and stigma. Conversely, being single was significantly associated with a greater degree of negative emotions and stigma beliefs among men. These findings suggest the need to re-frame messages that both men and women receive regarding human papillomavirus. © The Author(s) 2013.

  9. The fanconi anemia pathway limits human papillomavirus replication.

    PubMed

    Hoskins, Elizabeth E; Morreale, Richard J; Werner, Stephen P; Higginbotham, Jennifer M; Laimins, Laimonis A; Lambert, Paul F; Brown, Darron R; Gillison, Maura L; Nuovo, Gerard J; Witte, David P; Kim, Mi-Ok; Davies, Stella M; Mehta, Parinda A; Butsch Kovacic, Melinda; Wikenheiser-Brokamp, Kathryn A; Wells, Susanne I

    2012-08-01

    High-risk human papillomaviruses (HPVs) deregulate epidermal differentiation and cause anogenital and head and neck squamous cell carcinomas (SCCs). The E7 gene is considered the predominant viral oncogene and drives proliferation and genome instability. While the implementation of routine screens has greatly reduced the incidence of cervical cancers which are almost exclusively HPV positive, the proportion of HPV-positive head and neck SCCs is on the rise. High levels of HPV oncogene expression and genome load are linked to disease progression, but genetic risk factors that regulate oncogene abundance and/or genome amplification remain poorly understood. Fanconi anemia (FA) is a genome instability syndrome characterized at least in part by extreme susceptibility to SCCs. FA results from mutations in one of 15 genes in the FA pathway, whose protein products assemble in the nucleus and play important roles in DNA damage repair. We report here that loss of FA pathway components FANCA and FANCD2 stimulates E7 protein accumulation in human keratinocytes and causes increased epithelial proliferation and basal cell layer expansion in the HPV-positive epidermis. Additionally, FANCD2 loss stimulates HPV genome amplification in differentiating cells, demonstrating that the intact FA pathway functions to restrict the HPV life cycle. These findings raise the possibility that FA genes suppress HPV infection and disease and suggest possible mechanism(s) for reported associations of HPV with an FA cohort in Brazil and for allelic variation of FA genes with HPV persistence in the general population.

  10. Oropharyngeal perinatal colonization by human papillomavirus.

    PubMed

    Sánchez-Torices, María Soledad; Corrales-Millan, Rocío; Hijona-Elosegui, Jesús J

    2016-01-01

    Human papillomavirus (HPV) infection is the most common human sexually transmitted disease. It is clinically relevant because this condition is necessary for the development of epithelial cervical cancer, and it is also a factor closely associated with the occurrence of diverse tumours and various benign and malignant lesions of the head and neck area. The infective mechanism in most of these cases is associated with sexual intercourse, but there is recent scientific evidence suggesting that HPV infection may also be acquired by other routes of infection not necessarily linked to sexual contact. One of them is vertical transmission from mother to child, either during pregnancy or at the time of delivery. The aim of our research was to study maternal-foetal HPV transmission during childbirth in detail, establishing the rate of oropharyngeal neonatal HPV in vaginal deliveries. The presence and type of HPV viral DNA at the time of delivery in samples of maternal cervical secretions, amniotic fluid, venous cord blood samples and neonatal oropharynx in pregnant women (and their babies) were determined. The rate of oropharyngeal neonatal HPV colonization in vaginal deliveries was 58.24%. The maternal and neonatal HPV colonization mechanism is essentially, but not exclusively, transvaginal. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  11. [Human papillomavirus nonavalent vaccine. Update 2017].

    PubMed

    Bosch, F X; Moreno, D; Redondo, E; Torné, A

    Human papillomavirus (HPV) is the causative agent of 5% of human cancers. HPV infection is necessary for the development of cervical cancer and is responsible of a variable percentage of cancers of anus, vulva, vagina, penis, and oropharynx. Since 2007, 2 vaccines against HPV have been commercially available in Spain: bivalent (HPV types 16/18), and tetravalent (HPV types 6/11/16/18). In order to extend the protection afforded by HPV vaccines, a clinical program was launched in 2006 for the new nonavalent vaccine, including 9 HPV types (6/11/16/18/31/33/45/52/58). These types are responsible for 90% of cervical cancers, 82% of high-grade ano-genital pre-cancerous lesions, and 90% of genital warts. The purpose of this publication is to provide healthcare professionals with the scientific evidence that supports the new vaccine, as well as the clinical value that it offers in our environment. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Human Papillomavirus in Brazilian women with and without cervical lesions

    PubMed Central

    2011-01-01

    Background Human Papillomavirus (HPV) high-risk (HR) types are the causal factor for cervical cancer and premalignant dysplasia. Data on frequency of HPV types provide a basis to design and evaluate HPV prevention programs. Taking into account the heterogeneity of HPV types across and within populations this study aims to access the HPV frequency in Brazilian women. Results We identified 24 different types of HPV, including a Betapapillomavirus and a likely new type, previously reported, from 132 women positive for the virus analysed by Hybrid Capture II assay. These women were infected by a single or multiple HPV types and 142 HPV strains were identified. HR types were found in 75% of women and HPV types 16, 18, 45, 58, and 66 had the highest frequency. Significant differences in frequency of HR HPV types were found for presence of cervical lesions, and for different HPV species and women age. Conclusions Compared with previous studies in Brazil, our data indicated differences in frequency and HPV type diversity, a significant association of other HR-types but HPV16 and 18 and cervical lesions, and a trend for distinct distribution of HPV types by age. PMID:21208414

  13. Pathogenesis of human papillomavirus-associated mucosal disease.

    PubMed

    Groves, Ian J; Coleman, Nicholas

    2015-03-01

    Human papillomaviruses (HPVs) are a necessary cause of carcinoma of the cervix and other mucosal epithelia. Key events in high-risk HPV (HRHPV)-associated neoplastic progression include persistent infection, deregulated expression of virus early genes in basal epithelial cells and genomic instability causing secondary host genomic imbalances. There are multiple mechanisms by which deregulated virus early gene expression may be achieved. Integration of virus DNA into host chromosomes is observed in the majority of cervical squamous cell carcinomas (SCCs), although in ∼15% of cases the virus remains extrachromosomal (episomal). Interestingly, not all integration events provide a growth advantage to basal cervical epithelial cells or lead to increased levels of the virus oncogenes E6 and E7, when compared with episome-containing basal cells. The factors that provide a competitive advantage to some integrants, but not others, are complex and include virus and host contributions. Gene expression from integrated and episomal HRHPV is regulated through host epigenetic mechanisms affecting the virus long control region (LCR), which appear to be of functional importance. New approaches to treating HRHPV-associated mucosal neoplasia include knockout of integrated HRHPV DNA, depletion of virus transcripts and inhibition of virus early gene transcription through targeting or use of epigenetic modifiers. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  14. [Relationship between nasal inverted papilloma and human papillomavirus subtypes].

    PubMed

    Sun, Pu; Chen, Xiao-ping; Pei, Fei; Ma, Rui-xia; Zhang, Yi; Chen, Qun; Dong, Wei-gang; Chen, Wei-xiang; Huang, Hui-li

    2010-04-01

    To study the distribution of human papillomavirus (HPV) subtypes in nasal inverted papilloma (NIP), and to evaluate the relationship between HPV and NIP. Twenty-one HPV subtypes were detected in paraffin-embedded tissues of 101 cases of NIP by flow through hybridization and gene chip (HybriMax), 24 cases of normal nasal mucosa were used as controls. HPV positive rates of NIP were 64.36% (65/101). Benign NIP group, NIP with atypical hyperplasia group, NIP with cancerous group of HPV positive rates were 59.7% (46/77), 81.8% (18/22) and 50% (1/2) respectively. The control group was negative (0/24). The comparison between NIP group and control group was statistically significant (chi(2) = 32.178, P < 0.05). Benign NIP group and NIP with atypical hyperplasia group were compared, but no statistically significance (chi(2) = 3.649, P = 0.056) was found. The constituent ratio of benign NIP group and NIP with atypical hyperplasia group in high, low-risk HPV subtypes infections was compared, a statistically significance (chi(2) = 10.412, P < 0.05) was found. The occurrence of NIP was related with HPV infection. High-risk HPV subtype infections or multiple infections will prompt benign NIP to NIP with atypical hyperplasia. Understanding the distribution of HPV subtypes in the NIP is helpful to predict the clinical behavior.

  15. Human papillomavirus and invasive cervical cancer in Brazil.

    PubMed Central

    Eluf-Neto, J.; Booth, M.; Muñoz, N.; Bosch, F. X.; Meijer, C. J.; Walboomers, J. M.

    1994-01-01

    A hospital-based case-control study was undertaken to examine the role of human papillomavirus (HPV) in the development of invasive cervical cancer in Brazil. The study included 199 histologically confirmed incident cases and 225 age-frequency-matched controls selected from a wide range of diagnostic categories. A polymerase chain reaction technique was used to detect HPV DNA in cervical specimens collected with spatula and brush. HPV DNA was detected in 84% of the cases compared with 17% of controls. Grouping HPV types 16, 18, 31 and 33, 66% of the cases were positive compared with only 6% of the controls. In addition to HPV, number of sexual partners, early age at first intercourse, parity and duration of oral contraceptive use were significantly associated with an increased risk of cervical cancer. A history of previous Papanicolaou smears was significantly associated with a decreased risk. After adjustment, only presence of HPV DNA, parity and history of previous smears remained as independent risk factors. The adjusted odds ratios of cervical cancer associated with HPV 16, 18, 31, and 33 was 69.7 (95% confidence interval 28.7-169.6) and with unidentified types was 12.0 (5.1-28.5). The very high risks found in this study further implicate this virus in the aetiology of cervical cancer. PMID:8286192

  16. Human papillomavirus in men: comparison of different genital sites

    PubMed Central

    Aguilar, L V; Lazcano‐Ponce, E; Vaccarella, S; Cruz, A; Hernández, P; Smith, J S; Muñoz, N; Kornegay, J R; Hernández‐Avila, M; Franceschi, S

    2006-01-01

    Objective To elucidate which anatomical sites need to be sampled to detect human papillomavirus (HPV) infection in the lower male genital tract. Method In an HPV survey of Mexican soldiers (median age 24 years; range 16–50 years), a cell sample from 2 cm deep into the distal urethra (group 1; n = 168 men), or 0.5 cm deep into the meatus urethralis (group 2; n = 414 men) was collected, along with a sample from the external genitalia. The different samples were tested for 27 HPV types using a polymerase chain reaction based strip assay. Results HPV DNA was detected more frequently in external genitalia samples (46.4%) than in the urethra (20.8%) or meatus samples (12.1%). Lack of samples from the urethra or meatus would have led to 5.1% and 1.5% false HPV negative results, respectively. The most frequently detected high risk HPV types (HPV 59, 52, 51, and 16) were similar in different sites, whereas low risk types were found rarely in urethra samples. Conclusions The addition of cell samples from the meatus to those from external genitalia contributed negligibly to the evaluation of the prevalence of HPV in men. HPV detection was slightly improved by the addition of urethra samples, but the gain may not justify the discomfort of the procedure in large epidemiological studies. PMID:16461598

  17. Prevalence of human papillomavirus infection in Italian and immigrant women.

    PubMed

    Paba, P; Morosetti, G; Criscuolo, A A; Chiusuri, V; Marcuccilli, F; Sesti, F; Piccione, E; Perno, C F; Ciotti, M

    2012-01-01

    Human papillomavirus (HPV) is the most common sexually transmitted agent worldwide. Prevalence varies according to the geographic regions, and is highest in developing countries. Geographic differences exist also in the detection rate of oncogenic types in malignant cervical lesions. In this study, the prevalence of HPV infection as well as the spectrum of HPV types was evaluated in Italian and immigrant women of the urban area of Rome. Several risk factors (age at first intercourse, number of partners, smoking, pregnancy, age at first pregnancy, contraception, education, and menarche) were taken into consideration. Overall, there was a high prevalence of HPV infection in the two groups studied. No significant differences were observed in the spectrum of HPV types detected. HPV 16 and 18 were the types detected more frequently in both groups. Interestingly, HPV 54 and 70 were found only in the immigrants. Whether this finding reflects a recent introduction of these HPV types in the population studied remains to be established. Monitoring of HPV types in the population is advisable, especially in countries like Italy which is a destination and a gateway for immigrants directed towards north and central Europe. The introduction of high risk HPV variants may have a clinical impact and affect the diagnostic procedures.

  18. Human papillomavirus (HPV): making the case for 'Immunisation for All'.

    PubMed

    Prue, G; Lawler, M; Baker, P; Warnakulasuriya, S

    2016-08-05

    Human papillomavirus (HPV) contributes to the most common sexually transmitted infections, with repeated and persistent infection with particular types causing disease in both men and women. Infection with low-risk HPV types can lead to genital warts and benign lesions of the oral cavity, while high-risk types can cause various HPV-related malignancies. The incidence of head and neck cancers has been rising in the past number of decades mostly due to oropharyngeal cancer linked to HPV infection. HPV vaccination has been shown to be effective for cervical and other anogenital HPV-related cancers, and there is significant potential for HPV vaccination to prevent oropharyngeal cancers, given that the HPV types implicated in this disease can be protected against by the HPV vaccine. Few countries have implemented a universal HPV vaccination programme for males and females, with many countries arguing that female-only vaccination programmes protect males via herd immunity and that men who have sex with men will be protected via targeted vaccination programmes. We argue these may be limited in their effectiveness. We propose that the most effective, practical, ethical and potentially cost-effective solution is universal HPV vaccination that might lead to control of HPV-related diseases in men and women alike.

  19. Laboratory and clinical aspects of human papillomavirus testing

    PubMed Central

    Chan, Paul K.S.; Picconi, María Alejandra; Cheung, Tak Hong; Giovannelli, Lucia; Park, Jong Sup

    2012-01-01

    Human papillomavirus (HPV) infection is associated with a wide spectrum of disease that ranges from self-limited skin warts to life-threatening cancers. Since HPV plays a necessary etiological role in cervical cancer, it is logical to use HPV as a marker for early detection of cervical cancer and precancer. Recent advances in technology enable the development of high-throughput HPV assays of different formats, including DNA-based, mRNA-based, high-risk group-specific and type-specific methods. The ultimate goal of these assays is to improve the accuracy and cost-effiectiveness of cervical screening programs. HPV testing has several potential advantages compared to cytology-based screening. However, since the cancer to transient infection ratio is always low in the general population, HPV test results are bound to have a low positive predictive value that may subject women to unnecessary follow-up investigations. The wide-spread administration of prophylactic HPV vaccine will substantially decrease the incidence of cancer and precancer. This poses a number of challenges to cytology-based screening, and the role of HPV testing is expected to increase. Finally, apart from technical and cost-effiectiveness considerations, one should also keep in mind the psycho-social impact of using sexually-transmitted agents as a marker for cancer screening. PMID:22913405

  20. Prospects and prejudices of human papillomavirus vaccines in India.

    PubMed

    Das, Bhudev C; Hussain, Showket; Nasare, Vilas; Bharadwaj, Mausumi

    2008-05-23

    Cervical cancer is the most common cancer and a leading cause of cancer deaths among women in developing countries. The disease is caused due to persistent infection of one or more of about 15 high-risk human papillomaviruses (HR-HPVs), most commonly by HPV types 16/18. In India, over 98% of cervical cancer cases harbor HPV infection and HPV 16 is the type exclusively (80-90%) prevalent. Unlike the West, HPV infection is most common in women in their third decade (26-35 years) of sexual activity and invasive cancer also arises much later with a peak at about 45-55 years of age. Recently, two successful prophylactic HPV vaccines, a quadrivalent (HPV16/18/6/11) 'Gardasil' by Merck and a bivalent (HPV16/18) 'Cervarix' by GSK have been developed. Several other approaches including plant-based edible, pentameric capsomere-based intranasal and DNA-based vaccines have also been employed to develop prophylactic vaccines. Also, several therapeutic vaccines either protein/peptide based or DNA based are in clinical trials but are yet to establish their efficacy. Though there are several issues regarding implementation of the already developed vaccines in resource limited countries, efforts are being made to develop cost-effective second-generation vaccines. If cost minimized, HPV related new technologies involved in screening tests and vaccines are expected to reduce incidence of cervical cancer and deaths it causes in women from developing countries.

  1. Human papillomavirus vaccination induces neutralising antibodies in oral mucosal fluids.

    PubMed

    Handisurya, A; Schellenbacher, C; Haitel, A; Senger, T; Kirnbauer, R

    2016-02-16

    Mucosal human papillomaviruses (HPV) are a major cause of cancers and papillomas of the anogenital and oropharyngeal tract. HPV-vaccination elicits neutralising antibodies in sera and cervicovaginal secretions and protects uninfected individuals from persistent anogenital infection and associated diseases caused by the vaccine-targeted HPV types. Whether immunisation can prevent oropharyngeal infection and diseases and whether neutralising antibodies represent the correlate of protection, is still unclear. We determined IgG and neutralising antibodies against low-risk HPV6 and high-risk HPV16/18 in sera and oral fluids from healthy females (n=20) before and after quadrivalent HPV-vaccination and compared the results with non-vaccinated controls. HPV-vaccination induced type-specific antibodies in sera and oral fluids of the vaccinees. Importantly, the antibodies in oral fluids were capable of neutralising HPV pseudovirions in vitro, indicating protection from infection. The increased neutralising antibody levels against HPV16/18 in sera and oral fluids post-vaccination correlated significantly within an individual. We provide experimental proof that HPV-vaccination elicits neutralising antibodies to the vaccine-targeted types in oral fluids. Hence, immunisation may confer direct protection against type-specific HPV infection and associated diseases of the oropharyngeal tract. Measurement of antibodies in oral fluids represents a suitable tool to assess vaccine-induced protection within the mucosal milieu of the orophayrynx.

  2. Host defenses against human papillomaviruses: lessons from epidermodysplasia verruciformis.

    PubMed

    Orth, G

    2008-01-01

    Epidermodysplasia verruciformis (EV) is a rare, autosomal recessive genodermatosis associated with a high risk of skin carcinoma (MIM 226400). EV is characterized by the abnormal susceptibility of otherwise healthy patients to infection by specific, weakly virulent human papillomaviruses (HPVs), including the potentially oncogenic HPV-5. Inactivating mutations in either of the related EVER1/TMC6 and EVER2/TMC8 genes cause most EV cases. New insights in EV pathogenesis have been gained from the following recent observations: (1) EV-specific HPVs (betapapillomaviruses) are defective for an important growth-promoting function encoded by an E5/E8 gene present in other HPVs, and inactivation of EVER proteins may compensate for the missing viral function; (2) the transmembrane viral E5/E8 and cellular EVER proteins interact both with the zinc transporter ZnT1, and are likely to modulate zinc homeostasis. EV may thus represent a primary deficiency in intrinsic, constitutive immunity to betapapillomaviruses, or constitute a primary deficiency in innate immunity (or both). Keratinocytes, the home cells of HPVs, are likely to play a central role in both cases. An important issue is to establish which cellular genes involved in intrinsic and innate antiviral responses play a part in the outcome of infections with other HPV types, such as genital oncogenic HPVs.

  3. Race, ethnicity, and income factors impacting human papillomavirus vaccination rates.

    PubMed

    Jeudin, Patricia; Liveright, Elizabeth; Del Carmen, Marcela G; Perkins, Rebecca B

    2014-01-01

    Human papillomavirus (HPV) infection and cervical cancer disproportionately affect low-income and minority women. HPV vaccines have the potential to either reduce or exacerbate racial disparities in HPV-related diseases and cervical cancers, depending on the equitability of vaccine uptake. This review aims to identify barriers and facilitators of equitable uptake of HPV vaccination among low-income and minority girls. This review discusses factors related to race, ethnicity, and income that are associated with initiation and completion rates of the 3-dose HPV vaccine series and presents targets for intervention. We reviewed relevant English-language literature to identify current vaccination rates and factors associated with vaccine uptake. Study findings related to race (black, Latino, Asian), and incomes were summarized. Current trends in the United States indicate low uptake among all adolescents, and that rates stagnated between 2011 and 2012. Low-income and minority adolescents are equally or more likely to start the HPV vaccination series than are white and higher-income adolescents, but are less likely to complete all 3 shots. Provider recommendation is a key factor in HPV vaccination, and minorities are less likely to report receiving recommendations for HPV vaccination. As black, Hispanic, and Asian populations continue to grow in the United States over the next several decades, it is imperative that we not only improve HPV vaccination rates overall, but also focus on high-risk populations to prevent an increase in cervical cancer disparities. © 2014 Published by Elsevier HS Journals, Inc.

  4. Bacterial Vaginosis and the Natural History of Human Papillomavirus

    PubMed Central

    King, Caroline C.; Jamieson, Denise J.; Wiener, Jeffrey; Cu-Uvin, Susan; Klein, Robert S.; Rompalo, Anne M.; Shah, Keerti V.; Sobel, Jack D.

    2011-01-01

    Objective. To evaluate associations between common vaginal infections and human papillomavirus (HPV). Study Design. Data from up to 15 visits on 756 HIV-infected women and 380 high-risk HIV-uninfected women enrolled in the HIV Epidemiology Research Study (HERS) were evaluated for associations of bacterial vaginosis, trichomoniasis, and vaginal Candida colonization with prevalent HPV, incident HPV, and clearance of HPV in multivariate analysis. Results. Bacterial vaginosis (BV) was associated with increased odds for prevalent (aOR = 1.14, 95% CI: 1.04, 1.26) and incident (aOR = 1.24, 95% CI: 1.04, 1.47) HPV and with delayed clearance of infection (aHR = 0.84, 95% CI: 0.72, 0.97). Whereas BV at the preceding or current visit was associated with incident HPV, in an alternate model for the outcome of incident BV, HPV at the current, but not preceding, visit was associated with incident BV. Conclusion. These findings underscore the importance of prevention and successful treatment of bacterial vaginosis. PMID:21869857

  5. [Cervical infection epidemiology of human papillomavirus in Ushuaia, Argentina].

    PubMed

    Sijvarger, C C; González, J V; Prieto, A; Messmer, A G; Mallimaci, M C; Alonio, V L; Teyssié, A R; Picconi, M A

    2006-01-01

    Genital infection with human papillomavirus (HPV) is decisive in the causation of cervical cancer. In order to evaluate the epidemiology of HPV infection in Ushuaia, Province of Tierra del Fuego, Argentina, 132 endocervical cytobrushes from preneoplastic and neoplastic cases and controls were studied. Detection and typing of the viral genome was performed by polymerase chain reaction, combined with a restriction fragment length polymorphism assay or hybridization. The overall prevalence of HPV infection was 41% in the population examined, with a frequency of 26% in the controls and 71% in the cases under study. The 14-24 age group showed the highest HPV prevalence. The most common viral types in the infected population were HPV 16 (23%), HPV 18 (11%), HPV 33 (8%) and HPV 35 (8%), while high risk viral types were detected in 30% of the samples, 16% of the controls and 60% of the cases. This study provides the first data on the predominant viral types in Ushuaia. Our results show lower levels of infection than in regions with a high incidence of cervical cancer, HPV 16 being the most prevalent viral type. This research may be useful for selecting a specific vaccine targeting the population examined.

  6. Human papillomavirus variants among Inuit women in northern Quebec, Canada

    PubMed Central

    Gauthier, Barbara; Coutlée, Francois; Franco, Eduardo L.; Brassard, Paul

    2015-01-01

    Background Inuit communities in northern Quebec have high rates of human papillomavirus (HPV) infection, cervical cancer and cervical cancer–related mortality as compared to the Canadian population. HPV types can be further classified as intratypic variants based on the extent of homology in their nucleotide sequences. There is limited information on the distribution of intratypic variants in circumpolar areas. Objective Our goal was to describe the HPV intratypic variants and associated baseline characteristics. Design We collected cervical cell samples in 2002–2006 from 676 Inuit women between the ages of 15 and 69 years in Nunavik. DNA isolates from high-risk HPVs were sequenced to determine the intratypic variant. Results There were 149 women that were positive for HPVs 16, 18, 31, 33, 35, 45, 52, 56 or 58 during follow-up. There were 5 different HPV16 variants, all of European lineage, among the 57 women positive for this type. There were 8 different variants of HPV18 present and all were of European lineage (n=21). The majority of samples of HPV31 (n=52) were of lineage B. The number of isolates and diversity of the other HPV types was low. Age was the only covariate associated with HPV16 variant category. Conclusions These frequencies are similar to what was seen in another circumpolar region of Canada, although there appears to be less diversity as only European variants were detected. This study shows that most variants were clustered in one lineage for each HPV type. PMID:26653084

  7. Human papillomaviruses and non-melanoma skin cancer.

    PubMed

    McLaughlin-Drubin, Margaret E

    2015-04-01

    Human papillomaviruses (HPVs) infect the squamous epithelium and can induce benign and malignant lesions. To date, more than 200 different HPV types have been identified and classified into five genera, α, β, γ, μ, and ν. While high-risk α mucosal HPVs have a well-established role in cervical carcinoma and a significant percentage of other anogenital tract and oral carcinomas, the biology of the cutaneous β HPVs and their contribution to non-melanoma skin cancer (NMSC) has been less studied. Although the association of β HPV infection with NMSC in patients with a rare, genetically determined condition, epidermodysplasia verruciformis has been well established, the role of β HPV infection with NMSC in the normal population remains controversial. In stark contrast to α HPV-associated cancers, the presence of the β HPV genome does not appear to be mandatory for the maintenance of the malignant phenotype. Moreover, the mechanism of action of the β HPV E6 and E7 oncoproteins differs from the β HPV oncoproteins. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Human papillomavirus vaccination induces neutralising antibodies in oral mucosal fluids

    PubMed Central

    Handisurya, A; Schellenbacher, C; Haitel, A; Senger, T; Kirnbauer, R

    2016-01-01

    Background: Mucosal human papillomaviruses (HPV) are a major cause of cancers and papillomas of the anogenital and oropharyngeal tract. HPV-vaccination elicits neutralising antibodies in sera and cervicovaginal secretions and protects uninfected individuals from persistent anogenital infection and associated diseases caused by the vaccine-targeted HPV types. Whether immunisation can prevent oropharyngeal infection and diseases and whether neutralising antibodies represent the correlate of protection, is still unclear. Methods: We determined IgG and neutralising antibodies against low-risk HPV6 and high-risk HPV16/18 in sera and oral fluids from healthy females (n=20) before and after quadrivalent HPV-vaccination and compared the results with non-vaccinated controls. Results: HPV-vaccination induced type-specific antibodies in sera and oral fluids of the vaccinees. Importantly, the antibodies in oral fluids were capable of neutralising HPV pseudovirions in vitro, indicating protection from infection. The increased neutralising antibody levels against HPV16/18 in sera and oral fluids post-vaccination correlated significantly within an individual. Conclusions: We provide experimental proof that HPV-vaccination elicits neutralising antibodies to the vaccine-targeted types in oral fluids. Hence, immunisation may confer direct protection against type-specific HPV infection and associated diseases of the oropharyngeal tract. Measurement of antibodies in oral fluids represents a suitable tool to assess vaccine-induced protection within the mucosal milieu of the orophayrynx. PMID:26867163

  9. Human papillomavirus detection in cervical scrapes from women attended in the Family Health Program1

    PubMed Central

    Augusto, Everton Faccini; dos Santos, Larissa Silva; Oliveira, Ledy do Horto dos Santos

    2014-01-01

    Objectives to survey the prevalence of human papillomavirus, associated risk factors and genotype distribution in women who were referred to cervical cancer screening when attended in a Family Health Program. Method we conducted a cross-sectional survey, investigating 351 women. Polymerase chain reaction for DNA amplification and restriction fragment length polymorphism analysis were used to detect and typify the papillomavirus. Results virus infection was detected in 8.8% of the samples. Among the 21 different genotypes identified in this study, 14 were high risk for cervical cancer, and the type 16 was the most prevalent type. The infection was associated with women who had non-stable sexual partners. Low risk types were associated with younger women, while the high risk group was linked to altered cytology. Conclusion in this sample attended a Family Health Program, we found a low rate of papillomavirus infection. Virus frequency was associated to sexual behavior. However, the broad range of genotypes detected deserves attention regarding the vaccine coverage, which includes only HPV prevalent types. PMID:24553709

  10. Committee Opinion No. 704: Human Papillomavirus Vaccination.

    PubMed

    2017-06-01

    Human papillomavirus (HPV) is associated with anogenital cancer (including cervical, vaginal, vulvar, penile, and anal), oropharyngeal cancer, and genital warts. The HPV vaccination significantly reduces the incidence of anogenital cancer and genital warts. Despite the benefits of HPV vaccines, only 41.9% of girls in the recommended age group, and only 28.1% of males in the recommended age group have received all recom-mended doses. Compared with many other countries, HPV vaccination rates in the United States are unacceptably low. The U.S. Food and Drug Administration has approved three vaccines that are effective at preventing HPV infection. These vaccines cover 2, 4, or 9 HPV serotypes, respectively. Safety data for all three HPV vaccines are reassuring. The HPV vaccines are recommended for girls and boys aged 11-12 years and can be given to females and males up to age 26 years. The Advisory Committee on Immunization Practices and the American College of Obstetricians and Gynecologists recommend routine HPV vaccination for girls and boys at the target age of 11-12 years (but it may be given from the age of 9 years) as part of the adolescent immunization platform in order to help reduce the incidence of anogenital cancer and genital warts associated with HPV infection. Obstetrician-gynecologists and other health care providers should stress to parents and patients the benefits and safety of HPV vaccination and offer HPV vaccines in their offices.

  11. Molecular detection methods of human papillomavirus (HPV).

    PubMed

    Zaravinos, Apostolos; Mammas, Ioannis N; Sourvinos, George; Spandidos, Demetrios A

    2009-01-01

    Human papillomavirus (HPV) testing can identify women at risk of cervical cancer. Currently, molecular detection methods are the gold standard for identification of HPV. The three categories of molecular assays that are available are based on the detection of HPV DNA and include (1) non-amplified hybridization assays, such as Southern transfer hybridization (STH), dot blot hybridization (DB) and in situ hybridization (ISH); (2) signal amplified hybridization assays, such as hybrid capture assays (HC2); (3) target amplification assays, such as polymerase chain reaction (PCR) and in situ PCR. STH requires large amounts of DNA, is laborious and not reproducible, while ISH has only moderate sensitivity for HPV. The sensitivity of the HC2 assay is similar to that of PCR-based assays, with high sensitivity being achieved by signal rather than target amplification. PCR-based detection is both highly sensitive and specific. Since PCR can be performed on very small amounts of DNA, it is ideal for use on specimens with low DNA content. In the future, with the advance of technology, viral DNA extraction and amplification systems will become more rapid, more sensitive, and more automated.

  12. Human papillomavirus type 56-associated Bowen disease.

    PubMed

    Shimizu, A; Tamura, A; Abe, M; Amano, H; Motegi, S; Nakatani, Y; Hoshino, H; Ishikawa, O

    2012-11-01

    Some cases of human papillomavirus (HPV) type 56 infection in Bowen disease have been reported. However, the incidence and clinical characteristics are still unclear. To clarify the prevalence of HPV type 56-positive Bowen disease in our department and to characterize the clinical manifestations. Sixty-eight specimens of Bowen disease were examined by polymerase chain reaction using HPV consensus primers, and the amplified products were subjected to DNA sequence analyses. Moreover, positive samples were investigated by in situ hybridization. These findings were used to clarify the clinical characteristics of HPV-positive Bowen disease. Eight out of 68 specimens (12%) of Bowen disease were HPV-positive, of which six specimens were HPV type 56-positive. The HPV type 56-positive lesions were characterized by a longitudinal melanonychia or a deeply pigmented keratotic lesion. The remaining two specimens were genital Bowen disease in which HPV type 16 was detected. In situ hybridization demonstrated the positive cells in the upper layer of epidermis. The HPV type 56 detected in the samples of longitudinal melanonychia can be divided into at least into two types. This study determined the prevalence of HPV type 56-positive Bowen disease. Longitudinal melanonychia is the most characteristic manifestation of HPV type 56-associated Bowen disease. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

  13. Human papillomavirus and lung cancinogenesis: an overview.

    PubMed

    de Freitas, Antonio Carlos; Gurgel, Ana Pavla; de Lima, Elyda Golçalves; de França São Marcos, Bianca; do Amaral, Carolina Maria Medeiros

    2016-12-01

    Lung cancer is the most common cause of cancer deaths worldwide. Although tobacco smoking is considered to be the main risk factor and the most well-established risk factor for lung cancer, a number of patients who do not smoke have developed this disease. This number varies between 15 % to over one-half of lung cancer cases, and the deaths from lung cancer in non-smokers are increasing every year. There are many other agents that are thought to be etiological, including diesel exhaust exposure, metals, radiation, radon, hormonal factors, cooking oil, air pollution and infectious diseases, such as human papillomavirus (HPV). Studies in various parts of the world have detected HPV DNA at different rates in lung tumors. However, the role of HPV in lung cancer is still unclear. Thus, in this review, we investigated some molecular mechanisms of HPV protein activity in host cells, the entry of HPV into lung tissue and the possible route used by the virus to reach the lung cells.

  14. Requiring human papillomavirus vaccine for immigrant women.

    PubMed

    Hachey, Krista J; Allen, Rebecca H; Nothnagle, Melissa; Boardman, Lori A

    2009-11-01

    The Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommends human papillomavirus (HPV) vaccination of 11- to 12-year-old girls, with catch-up vaccination for girls and women aged 13 to 26 years. Although compulsory HPV vaccination is not currently mandated for any U.S. population, immigrant women aged 11-26 years are now required to receive the first injection of the vaccine (the full series consists of three doses) as a result of the 1996 Illegal Immigration Reform and Immigrant Responsibility Act. According to this law, immigrants applying for visas to enter the United States or to adjust their immigration status must receive the inoculations that the Advisory Committee on Immunization Practices recommends for U.S. residents. In the case of HPV, this law represents not only an undue burden on immigrant women, but also raises scientific and ethical questions regarding the benefit of vaccination in this population. Given these issues, immigrant women should not be required to provide documentation of HPV vaccination at the time of visa application or adjustment of immigration status.

  15. Human papillomavirus-related esophageal cancer survival

    PubMed Central

    Guo, Lanwei; Liu, Shuzheng; Zhang, Shaokai; Chen, Qiong; Zhang, Meng; Quan, Peiliang; Sun, Xi-Bin

    2016-01-01

    Abstract Background: Human papillomavirus (HPV) has been identified to be related to progression of esophageal cancer. However, the results remain controversial. A meta-analysis of epidemiologic studies was therefore conducted to address this issue. Methods: The electronic databases of MEDLINE and Excerpta Medica database were searched till April 30, 2016. Study-specific risk estimates were pooled using a random-effects model. Results: Ten studies involving a total of 1184 esophageal cancer cases were included in this meta-analysis. The pooled hazard ratio comparing HPV-positive to HPV-negative esophageal cancers was 1.03 (95% confidence interval 0.78–1.37), which was not significantly correlated with improved survival. However, HPV-16-positive patients might have a significantly favorable survival (hazard ratio 0.73, 95% confidence interval 0.44–1.21). Conclusion: The meta-analysis indicated that HPV infection may not be of prognostic utility in the evaluation of factors contributing to esophageal cancer. Further large prospective studies are encouraged to stratify survival analysis by HPV type. PMID:27861358

  16. Human papillomavirus related diseases in Malaysians.

    PubMed

    Cheah, P L

    1994-06-01

    The surge of information on the aetiological association of the human papillomavirus (HPV) with some epithelial tumours emanating from various centres has prompted the initiation of a large-scale retrospective study at the Department of Pathology, University Hospital Kuala Lumpur to determine the prevalence and importance of this virus in some epithelial tumours of Malaysian patients. A retrospective analysis of 100 cases of large cell non-keratinising carcinoma of the uterine cervix by in-situ hybridisation on archival formalin-fixed, paraffin-embedded tissue has revealed the presence of HPV type 16 in 47% and type 18 in 41% of cases. This gives an overall detection rate of 88% of the two HPV types most commonly encountered in cervical carcinomas. Except for the unusually high frequency of HPV 18 detected in the cases, the overall prevalence is comparable to that reported in studies from most other centres. Although this higher frequency of HPV 18 may be due to geographical variation, the selection of the large cell non-keratinising type of squamous cell cervical carcinoma for study remains a possible reason for this phenomenon. In comparison to cervical carcinomas, HPV appears to be uncommon in penile carcinomas and HPV 6 was detected in only 1 of 23 cases studied.

  17. Anaphylaxis following quadrivalent human papillomavirus vaccination.

    PubMed

    Brotherton, Julia M L; Gold, Mike S; Kemp, Andrew S; McIntyre, Peter B; Burgess, Margaret A; Campbell-Lloyd, Sue

    2008-09-09

    In 2007, Australia implemented the National human papillomavirus (HPV) Vaccination Program, which provides quadrivalent HPV vaccine free to all women aged 12-26 years. Following notification of 7 presumptive cases of anaphylaxis in the state of New South Wales, Australia, we verified cases and compared the incidence of anaphylaxis following HPV vaccination to other vaccines in comparable settings. We contacted all patients with suspected anaphylaxis and obtained detailed histories from telephone interviews and a review of medical records. A multidisciplinary team determined whether each suspected case met the standardized Brighton definition. Some participants also received skin-prick allergy testing for common antigens and components of the HPV vaccine. Of 12 suspected cases, 8 were classified as anaphylaxis. Of these, 4 participants had negative skin-prick test results for intradermal Gardasil. From the 269 680 HPV vaccine doses administered in schools, 7 cases of anaphylaxis were identified, which represents an incidence rate of 2.6 per 100 000 doses (95% CI 1.0-5.3 per 100 000). In comparison, the rate of identified anaphylaxis was 0.1 per 100 000 doses (95% CI 0.003-0.7) for conjugated meningococcal C vaccination in a 2003 school-based program. Based on the number of confirmed cases, the estimated rate of anaphylaxis following quadrivalent HPV vaccine was significantly higher than identified in comparable school-based delivery of other vaccines. However, overall rates were very low and managed appropriately with no serious sequelae.

  18. The paediatric story of human papillomavirus (Review)

    PubMed Central

    MAMMAS, IOANNIS N.; SOURVINOS, GEORGE; SPANDIDOS, DEMETRIOS A.

    2014-01-01

    Human papillomavirus (HPV) is composed of a particularly heterogeneous family of DNA viruses, which has gained much attention in recent years due to the discoveries of Professor Harald zur Hausen, who first identified a connection between HPV and cervical cancer. Professor Harald zur Hausen, the ‘Father of HPV Virology’, was the recipient of the 2008 Nobel Prize. HPV can be transmitted through physical contact via autoinoculation or fomites, sexual contact, as well as vertically from the HPV-positive mother to her newborn, causing subclinical or clinical infections. In infancy and childhood, HPV-associated clinical infections include skin warts, genital warts and juvenile recurrent respiratory papillomatosis, while cervical squamous intraepithelial lesions have also been reported among adolescent girls. To date, several research teams, worldwide, have extensively investigated HPV from the paediatric point of view. This primitive effort has been performed before the recent great expansion of paediatric HPV research due to the vaccination programmes against HPV, which were introduced into clinical practice in 2006. In this review article, we present a brief overview of paediatric HPV research after the first report in 1978 involving children in the research of HPV until the time point of this great expansion. In the future, it is expected that further unresolved issues will be addressed and clarified, as the paediatric story of HPV remains a challenging research target. PMID:25013461

  19. Human papillomavirus DNA in oral mucosal lesions.

    PubMed

    Giovannelli, Lucia; Campisi, Giuseppina; Lama, Anna; Giambalvo, Ornella; Osborn, John; Margiotta, Valerio; Ammatuna, Pietro

    2002-03-15

    This study determined the presence of human papillomavirus (HPV) DNA in oral mucosa cells from 121 patients with different types of oral mucosal lesions (13 squamous cell carcinomas, 59 potentially malignant lesions, 49 benign erosive ulcerative lesions) and from 90 control subjects. HPV DNA was detected by nested polymerase chain reaction, and genotype was determined by DNA sequencing. HPV prevalence was 61.5% in carcinomas, 27.1% in potentially malignant lesions, 26.5% in erosive ulcerative lesions, and 5.5% in control subjects. The risk of malignant or potentially malignant lesions was associated with HPV and was statistically significant. HPV-18 was found in 86.5% of HPV-positive lesions but was not associated with a particular type of lesion and was found in 80% of the HPV-positive control subjects. HPV infection was related to older age but not to sex, smoking, or alcohol use; the presence of lesions in the oral cavity increased the risk of HPV infection.

  20. Human papillomavirus vaccines and vaccine implementation.

    PubMed

    de Sanjosé, Silvia; Alemany, Laia; Castellsagué, Xavier; Bosch, F Xavier

    2008-11-01

    Countries are now challenged by the rapid development of vaccines aimed at the primary prevention of infections. In the years to come, several vaccines will need to be considered as potential candidates in routine immunization programs. Recently, two new vaccines against two/four types of human papillomavirus (HPV) have been commercialized. Bivalent HPV 16 and 18 (Cervarix) and quadrivalent HPV 6, 11, 16 and 18 (Gardasil) vaccines are now extensively used in some countries. These vaccines will prevent infection and long-running complications, such as cervical cancer, other HPV-related cancers and genital warts (for the quadrivalent vaccine). The beneficial effect of these vaccines will be largely observed in women. This article summarizes the burden of HPV preventable disease worldwide and briefly describes the impact of secondary prevention and the most relevant aspects of the current available vaccines, their efficacy and safety. Finally, some major aspects that are likely to impact the introduction of these vaccines around the world are outlined, with particular emphasis on developing countries.

  1. Anti-human papillomavirus therapeutics: facts & future.

    PubMed

    Bharti, Alok C; Shukla, Shirish; Mahata, Sutapa; Hedau, Suresh; Das, Bhudev C

    2009-09-01

    Even after 25 years of establishing Human Papillomavirus (HPV) as the causative agent for cervical cancer, effective treatment of HPV infection still unavailable. Comprehensive efforts especially for targeting HPV infection have been made only in recent years. Conventional physical ablation of HPV-induced lesions such as cryo-therapy, photo-therapy, LEEP, laser cone-biopsy and localized radiotherapy are shown to be effective to some extent in treating localized lesions where the removal of diseased tissue is associated with removal of transforming keratinocytes harboring HPV. Apart from currently available prophylactic vaccines which prevent the viral entry and should be given prior to viral exposure, several attempts are being made to develop therapeutic vaccines that could treat prevailing HPV infection. In addition, immunomodulators like interferons and imiquimod that have been shown to elicit cytokine milieu to enhance host immune response against HPV infection. Also, antiviral approaches such as RNA interference (RNAi) nucleotide analogs, antioxidants and herbal derivatives have shown effective therapeutic potential against HPV infection. These leads are being tested in pre-clinical and clinical studies. Present article provides a brief overview of conventional therapies for HPV-associated diseases. Potential of non-ablative anti-HPV treatment modalities that could prove useful for either elimination of HPV in early stages of infection when the virus is not integrated into the host cell genome or suppression of the expression of viral oncogenes that dys-regulate the host cell cycle following transformation is discussed.

  2. Introducing human papillomavirus vaccines - questions remain.

    PubMed

    Paavonen, Jorma; Lehtinen, Matti

    2008-01-01

    Genital human papillomavirus (HPV) infection and HPV-associated cervical and other anogenital cancers are significant public health problems. HPV 16 and HPV 18 are responsible for approximately 70% of all invasive cervical cancers worldwide. The first prophylactic HPV virus-like particle (VLP) vaccine against HPV types 6/11/16/18 was licensed in 2006 for girls and women aged 9-26 years. The second prophylactic HPV vaccine against HPV types 16 and 18 has been licensed this year. These vaccines are almost 100% effective in preventing infection and high-grade precancer associated with the HPV types included in the vaccine. The vaccines are well tolerated, safe, and highly immunogenic when given in three doses within 6 months. Efficacy of the vaccine against external vulvar and HPV-related vaginal lesions is also high. Even though the vaccine is highly effective against high-grade cervical, vaginal, or vulvar precancers, this only applies to women unexposed to these HPV types and only to high-grade intraepithelial lesions caused by these HPV types. Therefore, it is important to understand that the population impact of the vaccines will be much lower than vaccinating naive populations. Implementing HPV vaccine is a great opportunity but also a great challenge. However, mandatory HPV vaccination may raise many questions, and more answers are needed.

  3. Human papillomaviruses. Applications, caveats and prevention.

    PubMed

    Crum, Christopher P; Berkowitz, Ross S

    2002-07-01

    Unlike cervical cytology, human papillomavirus (HPV) testing provides an objective assessment of neoplasia risk. The major advantages of this technology are the potential for "reflex testing" (when used with liquid-based cytology); efficient exclusion of HPV-negative women, who can be triaged to yearly follow-up; and identification of HPV-positive women, who require colposcopic triage. However, practitioners should be aware that highly sensitive HPV tests will also identify many women with little or no immediate risk of significant neoplasia, may impose a psychosocial burden on the patient and may be used or interpreted inappropriately by both practitioners and patients. However, these caveats are similar to those inherent in any screening program involving a sexually transmitted disease, and the disadvantages of HPV testing will be minimized by attention to patient concerns and a keen awareness of the limitations of this technology. Ultimately, control of cervical cancer and its precursors rests with active prevention via vaccination programs targeting HPV. If successful, such programs could radically alter the number of women requiring triage for preinvasive disease and initiate a progressive decline in cervical cancer incidence.

  4. Human Papillomaviruses: Genetic Basis of Carcinogenicity

    PubMed Central

    Burk, Robert D.; Chen, Zigui; Van Doorslaer, Koenraad

    2009-01-01

    Persistent infection by specific oncogenic human papillomaviruses (HPVs) is established as the necessary cause of cervix cancer. DNA sequence differences between HPV genomes determine whether an HPV has the potential to cause cancer. Of the more than 100 HPV genotypes characterized at the genetic level, at least 15 are associated, to varying degrees, with cervical cancer. Classification based on nucleotide similarity places nearly all HPVs that infect the cervicovaginal area within the α-PV genus. Within this genus, phylogenetic trees inferred from the entire viral genome cluster all cancer-causing types together, suggesting the existence of a common ancestor for the oncogenic HPVs. However, in separate trees built from the early open reading frames (ORFs; i.e. E1, E2, E6, E7) or the late ORFs (i.e. L1, L2), the carcinogenic potential sorts with the early region of the genome, but not the late region. Thus, genetic differences within the early region specify the pathogenic potential of α-HPV infections. Since the HPV genomes are monophyletic and sites are highly correlated across the genome, diagnosis of oncogenic types and non-oncogenic types can be accomplished using any region across the genome. Here we review our current understanding of the evolutionary history of the oncogenic HPVs, in particular, we focus on the importance of viral genome heterogeneity and discuss the genetic basis for the oncogenic phenotype in some but not all α-PVs. PMID:19684441

  5. Human papillomavirus vaccination among adolescents in Georgia

    PubMed Central

    Underwood, Natasha L; Weiss, Paul; Gargano, Lisa M; Seib, Katherine; Rask, Kimberly J; Morfaw, Christopher; Murray, Dennis; DiClemente, Ralph J; Hughes, James M; Sales, Jessica M

    2015-01-01

    Human papillomavirus (HPV) vaccination coverage for adolescent females and males remains low in the United States. We conducted a 3-arm randomized controlled trial (RCT) conducted in middle and high schools in eastern Georgia from 2011–2013 to determine the effect of 2 educational interventions used to increase adolescent vaccination coverage for the 4 recommended adolescent vaccines: Tdap, MCV4, HPV and influenza. As part of this RCT, this article focuses on: 1) describing initiation and completion of HPV vaccine series among a diverse population of male and female adolescents; 2) assessing parental attitudes toward HPV vaccine; and 3) examining correlates of HPV vaccine series initiation and completion. Parental attitude score was the strongest predictor of HPV vaccine initiation among adolescents (adjusted odds ratio (aOR): 2.08; 95% confidence interval (CI): 1.80, 2.39). Other correlates that significantly predicted HPV series initiation were gender, study year, and intervention arm. Parental attitudes remained a significant predictor of receipt of 3 doses of HPV vaccine along with gender, race, school type and insurance type. This study demonstrates that positive parental attitudes are important predictors of HPV vaccination and critical to increasing coverage rates. Our findings suggest that more research is needed to understand how parental attitudes are developed and evolve over time. PMID:25912372

  6. Safety of human papillomavirus vaccines: a review

    PubMed Central

    Stillo, Michela; Carrillo Santisteve, Paloma; Lopalco, Pier Luigi

    2015-01-01

    Introduction: Between 2006 and 2009, two different human papillomavirus virus (HPV) vaccines were licensed for use: a quadrivalent (qHPVv) and a bivalent (bHPVv) vaccine. Since 2008, HPV vaccination programmes have been implemented in the majority of the industrialized countries. Since 2013, HPV vaccination has been part of the national programs of 66 countries including almost all countries in North America and Western Europe. Despite all the efforts made by individual countries, coverage rates are lower than expected. Vaccine safety represents one of the main concerns associated with the lack of acceptance of HPV vaccination both in the European Union/European Economic Area and elsewhere. Areas covered: Safety data published on bivalent and quadrivalent HPV vaccines, both in pre-licensure and post-licensure phase, are reviewed. Expert opinion: Based on the latest scientific evidence, both HPV vaccines seem to be safe. Nevertheless, public concern and rumors about adverse events (AE) represent an important barrier to overcome in order to increase vaccine coverage. Passive surveillance of AEs is an important tool for detecting safety signals, but it should be complemented by activities aimed at assessing the real cause of all suspect AEs. Improved vaccine safety surveillance is the first step for effective communication based on scientific evidence. PMID:25689872

  7. Human Papillomavirus Prevalence Is Associated With Socioeconomic Gradients Within a Medically Underserved Appalachian Region.

    PubMed

    Ware, S Lee; Crosby, Richard; Fisher, Rebecca; Hagensee, Michael E

    2017-07-13

    To assess type-specific prevalence of human papillomavirus (HPV) infection in a medically underserved Appalachian area and to determine whether gradients in poverty are associated with prevalence. Among 398 women, a validated assay tested self-collected cervicovaginal samples for 37 HPV types. Three economic strata were created based on household income: below the federal poverty level for 1 person, between the FPLs for families of 1 to 4 persons, and above the FPL for a family of 4. Prevalence was 55.6%, with 33% having at least 1 high-risk infection. Prevalence was 27.8% for 9-valent HPV vaccine-preventable types and 39.2% for multiple types. Compared with FPL for a family of 4, women with federal poverty level for 1 person had 3 times greater prevalence, 2.3 times greater prevalence of high-risk types, and 2.5 times greater prevalence of multiple types. Human papillomavirus prevalence was high, with one-third of the sample having at least 1 high-risk type and those in the lowest-income category being disproportionately infected.

  8. Human Papillomavirus Genotyping Testing Practice in 2014: Results of a College of American Pathologists National Survey.

    PubMed

    Zhao, Chengquan; Crothers, Barbara A; Ghofrani, Mohiedean; Li, Zaibo; Souers, Rhona J; Hussain, Mujtaba; Fan, Fang; Ocal, Idris Tolgay; Goodrich, Kelly; Shen, Rulong; Davey, Diane D

    2016-12-01

    - College of American Pathologists (CAP) surveys are used to establish national benchmarks for laboratories. - To investigate human papillomavirus (HPV) genotyping testing practice patterns in laboratories in 2014. - Data were analyzed from the CAP HPV Genotyping Practices Supplemental Questionnaire distributed to 749 laboratories participating in the CAP Human Papillomavirus (High Risk) for Cytology Program. - Six hundred four of 749 laboratories (80.6%) responded to the survey. More laboratories offered HPV genotyping testing and performed in-house HPV genotyping testing as compared to previous surveys. The Roche cobas HPV test was the most commonly used genotyping method (37.0%; 160 of 433), followed by Hologic Aptima HPV16 18/45 (26.1%; 113 of 433) and Hologic Cervista HPV16/18 (14.3%; 62 of 433). Most laboratories (287 of 399; 71.9%) offered HPV genotyping for high-risk HPV cases regardless of Papanicolaou (Pap) test results and patient age; this pattern was more common in laboratories using cobas. The remaining laboratories specifically offered testing to women with a negative Pap test result at age 30 years and older (65.2%, 73 of 112) or all ages (37.5%, 42 of 112). The median reporting rates of HPV16 and/or HPV18 positivity were 20.6%, 25.7%, 21.1%, and 57.4% for women with positive high-risk HPV adjunctive negative Pap results, atypical squamous cells of undermined significance, low-grade squamous intraepithelial lesion, and high-grade squamous lesion, respectively. - Human papillomavirus genotyping testing has increased. Roche cobas and Hologic Aptima genotype methods were the most common, and laboratories using cobas usually offered genotyping regardless of Pap test result and age. The data provide a baseline and trend of HPV genotyping test practices in 2014.

  9. Papillomaviruses

    PubMed Central

    Félez-Sánchez, Marta

    2015-01-01

    Papillomaviruses (PVs) are a numerous family of small dsDNA viruses infecting virtually all mammals. PVs cause infections without triggering a strong immune response, and natural infection provides only limited protection against reinfection. Most PVs are part and parcel of the skin microbiota. In some cases, infections by certain PVs take diverse clinical presentations from highly productive self-limited warts to invasive cancers. We propose PVs as an excellent model system to study the evolutionary interactions between the immune system and pathogens causing chronic infections: genotypically, PVs are very diverse, with hundreds of different genotypes infecting skin and mucosa; phenotypically, they display extremely broad gradients and trade-offs between key phenotypic traits, namely productivity, immunogenicity, prevalence, oncogenicity and clinical presentation. Public health interventions have been launched to decrease the burden of PV-associated cancers, including massive vaccination against the most oncogenic human PVs, as well as systematic screening for PV chronic anogenital infections. Anti-PVs vaccines elicit protection against infection, induce cross-protection against closely related viruses and result in herd immunity. However, our knowledge on the ecological and intrapatient dynamics of PV infections remains fragmentary. We still need to understand how the novel anthropogenic selection pressures posed by vaccination and screening will affect viral circulation and epidemiology. We present here an overview of PV evolution and the connection between PV genotypes and the phenotypic, clinical manifestations of the diseases they cause. This differential link between viral evolution and the gradient cancer-warts-asymptomatic infections makes PVs a privileged playground for evolutionary medicine research. PMID:25634317

  10. Prevalence of human papillomavirus in university young women

    PubMed Central

    MONTALVO, MARIA T.; LOBATO, ISMELDA; VILLANUEVA, HILDA; BORQUEZ, CELIA; NAVARRETE, DANIELA; ABARCA, JUAN; CALAF, GLORIA M.

    2011-01-01

    Cervical cancer is the second most prevalent female cancer worldwide. The majority of cases appear between the age of 30 and 50. Human papillomavirus (HPV) plays a central role in cervical cancer with 99.7% of HPV DNA identified in invasive cervical carcinomas. The prevalence of the HPV infection varies substantially among countries and according to age and lifestyle. HPV is a common sexually transmitted infection among males and females with a 70% higher incidence in sexually active females. This study aimed to determine the prevalence of human papillomavirus in young university women by analyzing the correlation between Papanicolaou (PAP)-stained cervical tests and HPV detection by genotyping, as well as other risk factors. A total of 200 women aged between 18 and 25 years were enrolled in this study, which took place between September 2008 and May 2009 at the Universidad de Tarapacá, Arica, Chile. Results of the PAP smears showed that 97.5% of cells had normal characteristics, although an inflammatory pattern was noted. The prevalence of generic HPV infection was 3.5% when testing for HPV DNA using the polymerase chain reaction (PCR) method. An analysis of the genotype of infected female individuals indicated that high-risk HPV types, such as HPV 16 and 31 were present in 42.84 and 14.29% of females, respectively, and low-risk types such as HPV 6, in 14.29%. Only one sample with differentiated non-HPV (14.29%) was found. A 95% correlation between PAP-stained cervical tests and the method of testing for HPV was observed. Using the PCR method, it was found that of the 195 negative PAP smears, 5 were positive for HPV and two of the samples that were positive for ASC-US were also positive. A significantly increased (P<0.05) HPV infection risk was observed in the 18–21 age group with a higher prevalence (71.40%) when compared to the 22–25 age group (28.6%). A significant (P<0.042) difference was found between smoking and HPV infection. In conclusion, a

  11. Ancillary Studies in Determining Human Papillomavirus Status of Squamous Cell Carcinoma of the Oropharynx: A Review

    PubMed Central

    Cantley, Richard L.; Gabrielli, Eleonora; Montebelli, Francesco; Cimbaluk, David; Gattuso, Paolo; Petruzzelli, Guy

    2011-01-01

    Squamous cell carcinoma (SCC) of the oral cavity and pharynx represents the sixth most common form of malignancy worldwide. A significant proportion of these cases are related to human papillomavirus (HPV) infection. In general, HPV-associated SCC is more commonly nonkeratinizing and poorly differentiated, whereas non-HPV-associated SCC is typically keratinizing and moderately differentiated. Nevertheless, significant overlap in morphology is seen between these two forms of SCC. The purpose of this paper is to highlight the utility of ancillary studies in the establishment of HPV status of oropharyngeal SCC, including p16 immunohistochemistry, high-risk HPV in situ hybridization, polymerase chain reaction, and newer HPV detection modalities. PMID:21772959

  12. Human papillomavirus infection in men who have sex with men in Lima, Peru.

    PubMed

    Quinn, Roswell; Salvatierra, Javier; Solari, Vicky; Calderon, Martha; Ton, Thanh G N; Zunt, Joseph R

    2012-12-01

    Human papillomavirus (HPV) infection among men who have sex with men (MSM) is the primary risk factor for anal cancer. Of 105 Peruvian MSM examined, 77.1% were infected with HPV; of these 79.0% were coinfected with two or more types and 47.3% were infected by a carcinogenic type. HPV types 53, 6, 16, and 58 were the most frequent HPV infections detected. High-risk HPV type infection was associated with sex work, HIV status, and having rectal chlamydial or gonorrheal infection. These findings support broadening HPV vaccine coverage and increasing surveillance for the development of cancer in MSM infected with HPV.

  13. Human Papillomavirus Infection in Men Who Have Sex with Men in Lima, Peru

    PubMed Central

    Quinn, Roswell; Salvatierra, Javier; Solari, Vicky; Calderon, Martha; Ton, Thanh G.N.

    2012-01-01

    Abstract Human papillomavirus (HPV) infection among men who have sex with men (MSM) is the primary risk factor for anal cancer. Of 105 Peruvian MSM examined, 77.1% were infected with HPV; of these 79.0% were coinfected with two or more types and 47.3% were infected by a carcinogenic type. HPV types 53, 6, 16, and 58 were the most frequent HPV infections detected. High-risk HPV type infection was associated with sex work, HIV status, and having rectal chlamydial or gonorrheal infection. These findings support broadening HPV vaccine coverage and increasing surveillance for the development of cancer in MSM infected with HPV. PMID:22519744

  14. Human papillomaviruses genotyping in plantar warts.

    PubMed

    de Planell-Mas, Elena; Martínez-Garriga, Blanca; Zalacain, Antonio Jesús; Vinuesa, Teresa; Viñas, Miguel

    2017-05-01

    Plantar warts are caused by human papillomaviruses (HPVs) and have been associated with several HPV genotypes. However, there are few studies focused exclusively on plantar warts. In this work, we aim to identify the HPV genotypes of plantar warts and explore their relation to demographic and clinical characteristics of patients. A total of 72 patients diagnosed with plantar warts were recruited at the Laser unit at Podiatric Hospital, University of Barcelona, Spain. Inner hyperkeratosis laminar sections of warts were collected and DNA of samples were extracted. Amplification of a conserved region of the HPV L1 gene was performed with the SK-Polymerase chain reaction method. DNA amplicons were sequenced and HPV types identified. The most prevalent genotypes detected among the 105 analyzed plantar warts were HPV-57 (37.1%), HPV-27 (23.8%), HPV-1a (20.9%), HPV-2 (15.2%), and HPV-65 (2.8%). The majority of patients (78%) presented one single plantar wart, whereas multiple warts were detected in 22.2% of patients. One patient with multiple warts presented HPV types from two different genera, suggesting the spread of warts by self-inoculation as well as by de novo infection. No significant differences between the number of warts in toes, midfoot and heel were found. The most prevalent HPV types detected in all areas belonged to the alpha genus. This work provides new insight on plantar warts and their associated HPV genotypes, and evidences the usefulness and reliability of both the sample collection procedure and the PCR method used for HPV detection and typing. J. Med. Virol. 89:902-907, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. [Human papillomavirus vaccine. Efficacy and safety].

    PubMed

    Bruni, Laia; Serrano, Beatriz; Bosch, Xavier; Castellsagué, Xavier

    2015-05-01

    Human papillomavirus (HPV) related disease remains a major cause of morbidity and mortality worldwide. Prophylactic vaccines have been recognized as the most effective intervention to control for HPV-related diseases. This article reviews the major phaseii/iii trials of the bivalent (HPVs16/18), quadrivalent (HPVs6/11/16/18), and the recently approved 9-valent vaccine (HPVs6/11/16/18/31/33/45/52/58). Large trials have been conducted showing the safety, immunogenicity and high efficacy of the bivalent and quadrivalent vaccines in the prevention of pre-invasive lesions and infection, especially when administered at young ages before exposure to HPV. Trials of the 9-valent vaccine have also demonstrated the safety, immunogenicity and efficacy of the vaccine in the prevention of infection and disease associated with the vaccine types, and its potential to substantially increase the overall prevention of HPV-related diseases. Post-licensure country reports have shown the recent and early impact of these vaccines at population level after the implementation of established HPV vaccination programs, including decreases in the prevalence of vaccine HPV types, the incidence of genital warts, and the incidence of high-grade cervical abnormalities. If widely implemented, current HPV vaccines may drastically reduce the incidence of cervical cancer and other HPV-related cancers and diseases. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  16. Committee opinion no. 588: human papillomavirus vaccination.

    PubMed

    2014-03-01

    The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommends that human papillomavirus (HPV) vaccination routinely be targeted to females and males aged 11 years or 12 years as part of the adolescent immunization platform to help reduce the incidence of anogenital cancers and genital warts associated with HPV infection. The quadrivalent HPV vaccine is approved for use in males and females, whereas the bivalent HPV vaccine is approved for use only in females. For those not vaccinated at the target age, catch-up vaccination is recommended up to age 26 years. The American College of Obstetricians and Gynecologists endorses these recommendations. Although obstetrician-gynecologists are not likely to care for many patients in the initial HPV vaccination target group, they have the opportunity to educate mothers about the importance of vaccinating their children at the recommended age and are critical to vaccinating adolescent girls and young women during the catch-up period. Obstetrician-gynecologists should advise patients and parents that HPV vaccines are most effective in preventing genital cancers when administered before the onset of sexual activity. However, sexually active individuals can receive some benefit from the vaccination because exposure to all HPV types prevented by the vaccines is unlikely in persons aged 13 years through 26 years. Although HPV vaccination in pregnancy is not recommended, neither is routine pregnancy testing before vaccination. Lactating women can receive either HPV vaccine. The need for ongoing cervical cytology screening should be emphasized in all women aged 21 years and older, even those who received HPV vaccination before the onset of sexual activity.

  17. Prevalence of high-risk human papilloma virus among women with hepatitis C virus before liver transplantation

    PubMed Central

    Tarallo, P.A.; Smolowitz, J.; Carriero, D.; Tarallo, J.; Siegel, A.; Jia, H.; Emond, J.C.

    2013-01-01

    Background We sought to assess the prevalence and risk factors for high-risk human papillomavirus (HPV) infection among female liver transplant (LT) candidates. Traditional health screening before LT listing has included Pap smear and is typically carried out by the patient’s local provider. The prevalence of high-risk HPV in this population has not been studied. Methods With Institutional Review Board approval, 62 LT candidates received a liquid-based Pap smear with high-risk HPV testing as part of their pre-transplant evaluation by a single provider. Clinical variables included age, ethnicity, insurance status, prior Pap smear, and HPV results, HPV risk factors including age of first intercourse, number of lifetime partners, last sexual activity, smoking, birth control pill use, history of sexually transmitted infections, human immunodeficiency virus status, immunosuppressive medication, medical diagnoses, prescribed medications, and history of hepatitis A, B, C, or D. Results The 62 women had a median age of 56 years, and 39% had high-risk behavior known to be associated with HPV. Ten of 62 patients (16.1%) had high-risk HPV at baseline screening, 5 of whom had atypical cytology. All of the patients who were positive for high-risk HPV had an etiology of hepatitis C virus (HCV) as the underlying cause of liver disease, with the majority (90%) having no history of high-risk behavior for HPV. In contrast, all patients with high-risk behavior who were HCV negative were HPV negative. Fisher’s exact test demonstrated a statistically significant relationship between HPV and HCV; odds ratio = 24.4, 95% confidence interval, P-value = 0.0013. None of the other potential risk factors were associated with HPV in this cohort. Conclusions In this study, we provide evidence of a strong association between HCV and HPV in LT candidates, which has not been previously reported. HPV positivity was observed in non-sexually active women, suggesting a reactivation of dormant HPV

  18. Human papillomavirus-related basaloid squamous cell carcinoma of the bladder associated with genital tract human papillomavirus infection.

    PubMed

    Ginori, Alessandro; Barone, Aurora; Santopietro, Rosa; Barbanti, Gabriele; Cecconi, Filippo; Tripodi, Sergio Antonio

    2015-02-01

    Basaloid squamous cell carcinoma is a biologically aggressive neoplasm mainly found in the head and neck region. Recently, four cases of basaloid squamous cell carcinoma of the bladder have been reported, and three of them occurred in patients with neurogenic bladder, repeated catheterizations and human papillomavirus infection of the urinary tract. To the best of our knowledge, none of the patients affected by basaloid squamous cell carcinoma of the bladder described in the literature had documented genital involvement by human papillomavirus. Herein, we describe the case of a woman with neurogenic bladder affected by basaloid squamous cell carcinoma of the bladder and by a concomitant genital tract human papillomavirus infection. © 2014 The Japanese Urological Association.

  19. Human papillomavirus detection in head and neck squamous cell carcinoma.

    PubMed

    Vietía, Dayahindara; Liuzzi, Juan; Avila, Maira; De Guglielmo, Zoraya; Prado, Yrneh; Correnti, María

    2014-01-01

    Human Papillomavirus (HPV) has been associated with benign and malignant lesions in different epitheliums. The relationship between specific genotypes of high-risk HPV and some human cancers is well established. The aim of this work was to detect the HPV genotypes present in head and neck squamous cell carcinoma (HNSCC). We evaluated 71 samples of patients with histopathological diagnosis of HNSCC. The DNA extraction was conducted with the QIAGEN commercial kit. HPV detection and genotyping were performed by reverse hybridisation (INNO-LiPA) following the commercial specifications. The mean age of the patients evaluated was 60.7 ± 13.11 years. The distribution of the lesions included 25 (35.20%) cases of squamous cell carcinoma (SCC) of the oral cavity, 23 (32.39%) of larynx, 16 (22.50%) of the oropharynx, 4 (5.63%) of paranasal sinus, and 2 (2. 80%) cases of SCC of the nostril. Of the patients, 78.9% were males, and of these 76% were tobacco users and 67.6% were alcohol consumers. The viral DNA was detected in 67.6% of the samples. The oral cavity and the larynx were the highest HPV-positivity sites with 35.40% and 29.10% respectively. The most frequent genotype was 16 as single infection (18.70%), or in combination with another HPV types. In the oral cavity and larynx the genotypes 16 or the combination 6 and 51 were present in 11.76% and 14.28%, respectively; and in the oropharynx the most frequent genotype was 16 in 22.50% of the cases, and in the paranasal sinus 50% presented infection with HPV-6. We observed that tumours with most advanced size and stage presented greater HPV positivity. This study shows a high percentage of HPV positivity in SCC is mainly associated with high-risk HPV. It is important to highlight that viral infection, especially HPV-16, could be a risk factor in HNSCC progression.

  20. Human papillomavirus detection in head and neck squamous cell carcinoma

    PubMed Central

    Vietía, Dayahindara; Liuzzi, Juan; Ávila, Maira; De Guglielmo, Zoraya; Prado, Yrneh; Correnti, María

    2014-01-01

    Introduction Human Papillomavirus (HPV) has been associated with benign and malignant lesions in different epitheliums. The relationship between specific genotypes of high-risk HPV and some human cancers is well established. The aim of this work was to detect the HPV genotypes present in head and neck squamous cell carcinoma (HNSCC). Methods We evaluated 71 samples of patients with histopathological diagnosis of HNSCC. The DNA extraction was conducted with the QIAGEN commercial kit. HPV detection and genotyping were performed by reverse hybridisation (INNO-LiPA) following the commercial specifications. Results The mean age of the patients evaluated was 60.7 ± 13.11 years. The distribution of the lesions included 25 (35.20%) cases of squamous cell carcinoma (SCC) of the oral cavity, 23 (32.39%) of larynx, 16 (22.50%) of the oropharynx, 4 (5.63%) of paranasal sinus, and 2 (2. 80%) cases of SCC of the nostril. Of the patients, 78.9% were males, and of these 76% were tobacco users and 67.6% were alcohol consumers. The viral DNA was detected in 67.6% of the samples. The oral cavity and the larynx were the highest HPV-positivity sites with 35.40% and 29.10% respectively. The most frequent genotype was 16 as single infection (18.70%), or in combination with another HPV types. In the oral cavity and larynx the genotypes 16 or the combination 6 and 51 were present in 11.76% and 14.28%, respectively; and in the oropharynx the most frequent genotype was 16 in 22.50% of the cases, and in the paranasal sinus 50% presented infection with HPV-6. We observed that tumours with most advanced size and stage presented greater HPV positivity. Conclusions This study shows a high percentage of HPV positivity in SCC is mainly associated with high-risk HPV. It is important to highlight that viral infection, especially HPV-16, could be a risk factor in HNSCC progression. PMID:25374623

  1. The role of human papillomavirus in squamous carcinoma of the head and neck.

    PubMed

    Li, Guojun; Sturgis, Erich M

    2006-03-01

    Human papillomavirus type-16 infection is associated with a significant portion of squamous carcinoma of the head and neck, particularly for the oropharynx and for those lacking the other risk factors of tobacco and alcohol. The link between human papillomavirus type-16 and carcinoma of the oropharynx is based on the identification of human papillomavirus type-16 in oropharyngeal tumors and the association of human papillomavirus type-16 with the risk of oropharyngeal cancer estimated in case-control epidemiologic studies. This review highlights the molecular mechanism of human papillomavirus carcinogenesis and the association of human papillomavirus type-16 as a risk factor for squamous cell carcinoma of the oropharynx as well as recent research efforts utilizing human papillomavirus as a biomarker of clinical outcomes.

  2. Apparent Diffusion Coefficient Histograms of Human Papillomavirus-Positive and Human Papillomavirus-Negative Head and Neck Squamous Cell Carcinoma: Assessment of Tumor Heterogeneity and Comparison with Histopathology.

    PubMed

    de Perrot, T; Lenoir, V; Domingo Ayllón, M; Dulguerov, N; Pusztaszeri, M; Becker, M

    2017-09-14

    Head and neck squamous cell carcinoma associated with human papillomavirus infection represents a distinct tumor entity. We hypothesized that diffusion phenotypes based on the histogram analysis of ADC values reflect distinct degrees of tumor heterogeneity in human papillomavirus-positive and human papillomavirus-negative head and neck squamous cell carcinomas. One hundred five consecutive patients (mean age, 64 years; range, 45-87 years) with primary oropharyngeal (n = 52) and oral cavity (n = 53) head and neck squamous cell carcinoma underwent MR imaging with anatomic and diffusion-weighted sequences (b = 0, b = 1000 s/mm(2), monoexponential ADC calculation). The collected tumor voxels from the contoured ROIs provided histograms from which position, dispersion, and form parameters were computed. Histogram data were correlated with histopathology, p16-immunohistochemistry, and polymerase chain reaction for human papillomavirus DNA. There were 21 human papillomavirus-positive and 84 human papillomavirus-negative head and neck squamous cell carcinomas. At histopathology, human papillomavirus-positive cancers were more often nonkeratinizing (13/21, 62%) than human papillomavirus-negative cancers (19/84, 23%; P = .001), and their mitotic index was higher (71% versus 49%; P = .005). ROI-based mean and median ADCs were significantly lower in human papillomavirus-positive (1014 ± 178 × 10(-6) mm(2)/s and 970 ± 187 × 10(-6) mm(2)/s, respectively) than in human papillomavirus-negative tumors (1184 ± 168 × 10(-6) mm(2)/s and 1161 ± 175 × 10(-6) mm(2)/s, respectively; P < .001), whereas excess kurtosis and skewness were significantly higher in human papillomavirus-positive (1.934 ± 1.386 and 0.923 ± 0.510, respectively) than in human papillomavirus-negative tumors (0.643 ± 0.982 and 0.399 ± 0.516, respectively; P < .001). Human papillomavirus-negative head and neck squamous cell carcinoma had symmetric normally distributed ADC histograms, which corresponded

  3. 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

  4. Nucleic acid tests for the detection of alpha human papillomaviruses.

    PubMed

    Poljak, Mario; Cuzick, Jack; Kocjan, Boštjan J; Iftner, Thomas; Dillner, Joakim; Arbyn, Marc

    2012-11-20

    Testing for high-risk types of alpha human papillomaviruses (HPV) is an invaluable part of clinical guidelines for cervical carcinoma screening, management and treatment. In this comprehensive inventory of commercial tests for detection of alpha-HPV, we identified at least 125 distinct HPV tests and at least 84 variants of the original tests. However, only a small subset of HPV tests has documented clinical performance for any of the standard HPV testing indications. For more than 75% of HPV tests currently on the market, no single publication in peer-reviewed literature can be identified. HPV tests that have not been validated and lack proof of reliability, reproducibility and accuracy should not be used in clinical management. Once incorporated in the lab, it is essential that the whole procedure of HPV testing is subject to continuous and rigorous quality assurance to avoid sub-optimal, potentially harmful practices. Manufacturers of HPV tests are urged to put more effort into evaluating their current and future products analytically, using international standards, and for clinical applications, using clinically validated endpoints. To assist with analytical validation, the World Health Organization is developing international standards for HPV types other than HPV16 and HPV18 and is planning development of external quality control panels specifically designed to be used for performance evaluation of current and future HPV tests. There is a need for more competitively priced HPV tests, especially for resource-poor countries, and uniform test validation criteria based on international standards should enable issuing more competitive and fair tender notices for purchasing. Automation systems allowing large-scale testing, as well as further increases in clinical performance, are the main needs in the further improvement of HPV tests. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine

  5. Evidence that human papillomavirus causes inverted papilloma is sparse.

    PubMed

    Justice, Jeb M; Davis, Kern M; Saenz, Daniel A; Lanza, Donald C

    2014-12-01

    Controversy exists regarding the pathogenesis of inverted papilloma as it relates to the involvement of human papillomavirus (HPV). The purpose of this report is to describe the prevalence of HPV in nondysplastic, "early inverted papilloma" and to summarize HPV detection rates in the general population and in other HPV related neoplasia. This case series report characterizes consecutive inverted papilloma patients from January 2005 to August 2012 with regard to smoking history, dysplasia, and HPV detection rates. Presence or absence of low/high risk HPV was determined by standardized in situ hybridization DNA probes. Medline literature review was performed to determine the prevalence of HPV in inverted papilloma without moderate or severe dysplasia. Thirty-six consecutive patients were identified with an average age of 63.6 (range, 40-84) years; gender: 23 men, 13 women. More than half (55%) were active or former smokers (14% active and 41% former). High/low risk HPV was present in 1 in 36 (2.7%) patients and 1 in 36 (2.7%) had mild dysplasia. In the literature review: (1) HPV was detected in 16.4% of inverted papilloma without dysplasia; (2) oral cavity HPV detection was 4.2% to 11.4% in the normal population; and (3) HPV was normally detected in 85% to 95% of HPV-related neoplasia. Given histological features of inverted papilloma and comparatively low detection rates of HPV in inverted papilloma without dysplasia (2.7%), as well as the summary of the world literature, HPV is not related to the initial pathogenesis of inverted papilloma or inverted papilloma's tendency to persist or recur. It is postulated that since inverted papilloma is more an inflammatory polyp, it is susceptible to secondary HPV infection because of its metaplasia. Tobacco and other causes of respiratory epithelium remodeling are more plausible explanations for the initial tissue transformation to inverted papilloma. © 2014 ARS-AAOA, LLC.

  6. Immune therapy for human papillomaviruses-related cancers.

    PubMed

    Rosales, Ricardo; Rosales, Carlos

    2014-12-10

    Human papillomaviruses (HPVs) are a large family of double strand DNA viruses comprising more than 180 types. Infection with HPV is very common and it is associated with benign and malignant proliferation of skin and squamous mucosae. Many HPVs, considered low-risk such as HPV 6 and 11, produce warts; while high-risk viruses, such as HPVs 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, and 58, induce tumors. About 5% of all cancers in men and women are associated with HPV infection. Because there are not antiviral drugs for HPV infection, current therapies for low-risk HPV infections involve physical removal of the lesion by cryotherapy, trichloracetic acid, laser, or surgical removal. Surgical procedures are effective in the treatment of pre-cancerous lesions, however after these procedures, many recurrences appear due to new re-infections, or to failure of the procedure to eliminate the HPV. In addition, HPV can inhibit recognition of malignant cells by the immune system, leading to the development of cancer lesions. When this occurs, radiotherapy and chemotherapy are then used. Unfortunately, about 50% of the HPV-cancer patients still die. In the past decade, a better knowledge of the natural history of the virus-host interaction and of the immune response against this viral infection has brought new therapeutic strategies geared to modulate the immune system to generate an efficient virus-specific cytotoxic response. Novel HPV protein-expressing vaccines have shown some significant clinical efficacy and systemic HPV-specific cytotoxic T cell responses. This review will describe the current status of the several therapeutic strategies used to treat HPV-induced lesions, and discuss the various new therapies now being tested.

  7. Immune therapy for human papillomaviruses-related cancers

    PubMed Central

    Rosales, Ricardo; Rosales, Carlos

    2014-01-01

    Human papillomaviruses (HPVs) are a large family of double strand DNA viruses comprising more than 180 types. Infection with HPV is very common and it is associated with benign and malignant proliferation of skin and squamous mucosae. Many HPVs, considered low-risk such as HPV 6 and 11, produce warts; while high-risk viruses, such as HPVs 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, and 58, induce tumors. About 5% of all cancers in men and women are associated with HPV infection. Because there are not antiviral drugs for HPV infection, current therapies for low-risk HPV infections involve physical removal of the lesion by cryotherapy, trichloracetic acid, laser, or surgical removal. Surgical procedures are effective in the treatment of pre-cancerous lesions, however after these procedures, many recurrences appear due to new re-infections, or to failure of the procedure to eliminate the HPV. In addition, HPV can inhibit recognition of malignant cells by the immune system, leading to the development of cancer lesions. When this occurs, radiotherapy and chemotherapy are then used. Unfortunately, about 50% of the HPV-cancer patients still die. In the past decade, a better knowledge of the natural history of the virus-host interaction and of the immune response against this viral infection has brought new therapeutic strategies geared to modulate the immune system to generate an efficient virus-specific cytotoxic response. Novel HPV protein-expressing vaccines have shown some significant clinical efficacy and systemic HPV-specific cytotoxic T cell responses. This review will describe the current status of the several therapeutic strategies used to treat HPV-induced lesions, and discuss the various new therapies now being tested. PMID:25493236

  8. Quadrivalent Human Papillomavirus Vaccine Effectiveness: A Swedish National Cohort Study

    PubMed Central

    2013-01-01

    Background Incidence of condyloma, or genital warts (GW), is the earliest possible disease outcome to measure when assessing the effectiveness of human papillomavirus (HPV) vaccination strategies. Efficacy trials that follow prespecified inclusion and exclusion criteria may not be fully generalizable to real-life HPV vaccination programs, which target a broader segment of the population. We assessed GW incidence after on-demand vaccination with quadrivalent HPV vaccine using individual-level data from the entire Swedish population. Methods An open cohort of girls and women aged 10 to 44 years living in Sweden between 2006 and 2010 (N > 2.2 million) was linked to multiple population registers to identify incident GW in relation to HPV vaccination. For vaccine effectiveness, incidence rate ratios of GW were estimated using time-to-event analyses with adjustment for attained age and parental education level, stratifying on age at first vaccination. Results A total of 124 000 girls and women were vaccinated between 2006 and 2010. Girls and women with at least one university-educated parent were 15 times more likely to be vaccinated before age 20 years than girls and women whose parents did not complete high school (relative risk ratio = 15.45, 95% confidence interval [CI] = 14.65 to 16.30). Among those aged older than 20 years, GW rates declined among the unvaccinated, suggesting that HPV vaccines were preferentially used by women at high risk of GW. Vaccination effectiveness was 76% (95% CI = 73% to 79%) among those who received three doses of the vaccine with their first dose before age 20 years. Vaccine effectiveness was highest in girls vaccinated before age 14 years (effectiveness = 93%, 95% CI = 73% to 98%). Conclusions Young age at first vaccination is imperative for maximizing quadrivalent HPV vaccine effectiveness. PMID:23486550

  9. Human papillomavirus testing for primary cervical cancer screening.

    PubMed

    Grce, Magdalena; Davies, Philip

    2008-09-01

    Cervical cancer is the second most common cancer in women worldwide and the seventh most common cause of cancer deaths in women in Europe. Today, we know how to prevent almost every case of this disease; organized cervical cancer screening based on the Papanicolaou or Pap smear has been proven to prevent 80% of cervical cancer deaths, while new technologies for the detection of the human papillomavirus (HPV) or the prevention of HPV infection offer the potential to make even more progress in the battle against this disease. Testing for carcinogenic or high-risk HPV types is gaining acceptance for the triage of women with borderline cytology and for follow-up after treatment of high-grade cervical lesions. Now, a number of large-scale randomized controlled trials have shown that HPV testing as a primary screening test can detect approximately 50% more high-grade lesions than the Pap test, albeit with a lower specificity if all HPV-positive women are followed up. However, alternative screening algorithms in which HPV-positive women are triaged with cytology have been shown to have equivalent specificity to the Pap test without compromising the increased sensitivity. Further advantages of HPV testing come from the fact that it is an objective and automatable test with a dichotomous result. These attributes can yield cost savings through reductions in staff numbers and simplification of quality control procedures while reducing turnaround times. In countries seeking to improve cervical cancer prevention, the implementation of HPV testing as the primary screening test with cytology for the triage of HPV-positive women is an option that should be fully evaluated. This review summarizes the recent advances in HPV testing in cervical cancer prevention.

  10. Prevalence of cervical human papillomavirus (HPV) infection in Vanuatu.

    PubMed

    Aruhuri, Bernadette; Tarivonda, Len; Tenet, Vanessa; Sinha, Rohit; Snijders, Peter J F; Clifford, Gary; Pang, James; McAdam, Margaret; Meijer, Chris J L M; Frazer, Ian H; Franceschi, Silvia

    2012-05-01

    To provide information on human papillomavirus (HPV) prevalence and the distribution of individual HPV types in Pacific Islands, we conducted a population-based survey in Vanuatu, South Pacific. Nine hundred and eighty-seven women between 18 and 64 years of age were included. GP5(+)/6(+)-mediated PCR assay was used for HPV testing. The prevalence of 44 HPV types was 28.4% corresponding to an age (world)-standardized prevalence of 25.0% [95% confidence interval (CI), 21.9%-28.0%]. The prevalence of high-risk (HR) HPV types was 21.7% (age-standardized prevalence of 19.2%; 95% CI, 16.4%-22.0%). Among 840 women with adequate cytologic results, 13.6% showed cervical abnormalities, including 3.6% with high-grade squamous intraepithelial lesions (HSIL) and 0.8% with invasive cervical carcinoma. HPV prevalence declined from 46.1% in women aged ≤21 to 15.3% in those ≥45 years. Being single was significantly associated with HPV positivity. HR HPV findings by PCR assay and hybrid capture 2 (HC2; conducted in Vanuatu) were moderately correlated (κ test = 0.59). The positive predictive values of HR HPV positivity for HSIL or worse were 27.6% for PCR and 35.2% for HC2 among women aged ≥30. Nearly half of screening-positive women could not be reevaluated mainly on account of the difficulty to trace back women. The availability of a rapid HPV testing method that allows see-and-treat approaches at the same visit would be, therefore, essential. On account of their high cumulative burden of cervical lesions, also women older than 40 years should be included in at least the first screening round in unscreened populations.

  11. Human papillomavirus infection in women from tlaxcala, Mexico.

    PubMed

    Velázquez-Márquez, Noé; Jaime Jiménez-Aranda, Lucio; Sánchez-Alonso, Patricia; Santos-López, Gerardo; Reyes-Leyva, Julio; Vallejo-Ruiz, Verónica

    2010-07-01

    Cervical cancer is an important health problem in women living in developing countries. Infection with some genotypes of human papillomavirus (HPV) is the most important risk factor associated with cervical cancer. Little information exists about HPV genotype distribution in rural and suburban regions of Mexico. Thus, we determined the prevalence of HPV genotypes in women from Tlaxcala, one of the poorest states in central Mexico, and we evaluated age infection prevalence and risk factors associated with cervical neoplasm. A cross-sectional study was conducted in 236 women seeking gynecological care at the Mexican Institute for Social Security in Tlaxcala, Mexico. Cervical scrapings were diagnosed as normal, low-grade, and high-grade squamous intraepithelial lesions (LGSIL, HGSIL). Parallel samples were used to detect HPV genotypes by PCR assays using type-specific primers for HPV 6, 11, 16, 18, and 31. An epidemiological questionnaire was applied. Prevalence of HPV infection was 31.3%. From the infected samples, prevalence of HPV 16 was 45.9%; HPV 18, 31.1%; HPV 31, 16.2%; HPV 6, 10.8%; HPV 11, 6.7%. With regard to age, the highest HPV prevalence (43.5%) was found in the 18- to 24-year-old group and the lowest (19%) in the 45- to 54-year-old group. None of the risk factors showed association with cervical neoplasia grade. HPV 16 was the most common in cervical lesions. HPV was present in 22% of normal samples and, of these, 82.6% represented high-risk HPVs. Tlaxcala showed HPV prevalence comparable to that of the largest cities in Mexico, with higher prevalence for HPV 31.

  12. Human Papillomavirus Infection in Women from Tlaxcala, Mexico

    PubMed Central

    Velázquez-Márquez, Noé; Jaime Jiménez-Aranda, Lucio; Sánchez-Alonso, Patricia; Santos-López, Gerardo; Reyes-Leyva, Julio; Vallejo-Ruiz, Verónica

    2010-01-01

    Cervical cancer is an important health problem in women living in developing countries. Infection with some genotypes of human papillomavirus (HPV) is the most important risk factor associated with cervical cancer. Little information exists about HPV genotype distribution in rural and suburban regions of Mexico. Thus, we determined the prevalence of HPV genotypes in women from Tlaxcala, one of the poorest states in central Mexico, and we evaluated age infection prevalence and risk factors associated with cervical neoplasm. A cross-sectional study was conducted in 236 women seeking gynecological care at the Mexican Institute for Social Security in Tlaxcala, Mexico. Cervical scrapings were diagnosed as normal, low-grade, and high-grade squamous intraepithelial lesions (LGSIL, HGSIL). Parallel samples were used to detect HPV genotypes by PCR assays using type-specific primers for HPV 6, 11, 16, 18, and 31. An epidemiological questionnaire was applied. Prevalence of HPV infection was 31.3%. From the infected samples, prevalence of HPV 16 was 45.9%; HPV 18, 31.1%; HPV 31, 16.2%; HPV 6, 10.8%; HPV 11, 6.7%. With regard to age, the highest HPV prevalence (43.5%) was found in the 18- to 24-year-old group and the lowest (19%) in the 45- to 54-year-old group. None of the risk factors showed association with cervical neoplasia grade. HPV 16 was the most common in cervical lesions. HPV was present in 22% of normal samples and, of these, 82.6% represented high-risk HPVs. Tlaxcala showed HPV prevalence comparable to that of the largest cities in Mexico, with higher prevalence for HPV 31. PMID:24031552

  13. Understanding suboptimal human papillomavirus vaccine uptake among ethnic minority girls.

    PubMed

    Bastani, Roshan; Glenn, Beth A; Tsui, Jennifer; Chang, L Cindy; Marchand, Erica J; Taylor, Victoria M; Singhal, Rita

    2011-07-01

    The introduction of human papillomavirus (HPV) vaccines represents a breakthrough in the primary prevention of cervical cancer. However, little is known about vaccination uptake and correlates among low-income, ethnic minority, and immigrant populations in the U.S. who may benefit most from the vaccine. Telephone interviews (N = 490) were conducted in six languages between January and November 2009 among mothers of vaccine-eligible girls (ages 9-18) using the Los Angeles County Department of Public Health, Office of Women's Health service referral hotline. HPV and vaccine awareness, knowledge, beliefs, barriers, and daughter's vaccine receipt were assessed. The sample consisted of low-income, uninsured, ethnic minority, and immigrant women. Only 29% of daughters initiated the vaccine and 11% received all three doses. No ethnic differences were observed in initiation or completion rates. Ethnic differences were observed in HPV awareness, perceived risk, and other vaccine-related beliefs. The strongest predictor of initiation was vaccine awareness (OR = 12.00). Daughter's age and reporting a younger acceptable age for vaccination were positively associated with initiation. Mothers of unvaccinated girls reported lacking information about the vaccine to make a decision (66%) and not knowing where they could obtain the vaccine (74%). Vaccination rates in this sample were lower than state and national estimates, and were associated with low levels of vaccine awareness. Interventions, including culturally targeted messaging, may be helpful for enhancing HPV-vaccine knowledge, modifying vaccine-related beliefs and increasing uptake. Our findings provide valuable guidance for developing interventions to address suboptimal HPV vaccination in high-risk groups. ©2011 AACR

  14. [Pathogenesis of human papillomavirus infection in patients with epidermodysplasia verruciformis].

    PubMed

    Liang, Si; Zuo, Ya-Gang; Wang, Bao-Xi

    2009-02-01

    Epidermodysplasia verruciformis (EV), a rare inherited disease, is believed to be associated with human papillomavirus (HPV) infection. EVER1/2 genes, dendritic cells, T lymphocytes, and the biological characteristics of HPV itself may play roles in the pathogenesis of HPV infection.

  15. Human papillomavirus-associated cancers: A growing global problem

    PubMed Central

    Bansal, Anshuma; Singh, Mini P; Rai, Bhavana

    2016-01-01

    Human papillomavirus (HPV) infection is linked with several cancers such as cancer cervix, vagina, vulva, head and neck, anal, and penile carcinomas. Although there is a proven association of HPV with these cancers, questions regarding HPV testing, vaccination, and treatment of HPV-related cancers continue to remain unanswered. The present article provides an overview of the HPV-associated cancers. PMID:27127735

  16. Focal epithelial hyperplasia caused by human papillomavirus 13.

    PubMed

    Saunders, Natasha R; Scolnik, Dennis; Rebbapragada, Anuradha; Koelink, Eric; Craw, Lindsey; Roth, Sherryn; Aronson, Leya; Perusini, Stephen; Silverman, Michael S

    2010-06-01

    Focal epithelial hyperplasia is a benign, papulo-nodular disease of the oral cavity. It is rare, affecting primarily Native American populations during childhood. It is closely associated with human papillomavirus 13 and 32. This report describes the diagnosis of 2 cases of focal epithelial hyperplasia in children from southern Guyana. The diagnosis was made using clinical criteria, polymerase chain reaction, and DNA sequencing.

  17. Development of a Human Papillomavirus Vaccination Intervention for Australian Adolescents

    ERIC Educational Resources Information Center

    Cooper, Spring C.; Davies, Cristyn; McBride, Kate; Blades, Joanna; Stoney, Tanya; Marshall, Helen; Skinner, S. Rachel

    2016-01-01

    Objective: Australia has implemented a nation-wide programme providing a human papillomavirus (HPV) vaccine to girls and boys through school-based programmes. Previous research has identified three distinct areas for attention: (1) lack of understanding about HPV and HPV vaccination, (2) young people's desire for involvement in decision-making…

  18. Intention of College Students to Receive the Human Papillomavirus Vaccine

    ERIC Educational Resources Information Center

    Richards, Keith

    2016-01-01

    Purpose: The purpose of this paper is to better understand what influences the intentions of college students to receive the human papillomavirus (HPV) vaccine. HPV is the most common sexually transmitted infection in the USA and cancers related to HPV are on the rise. Design/Methodology/Approach: A 2×2 experimental design was used to predict the…

  19. Human Papillomavirus Vaccine Intent and Uptake among Female College Students

    ERIC Educational Resources Information Center

    Patel, Divya A.; Zochowski, Melissa; Peterman, Stephanie; Dempsey, Amanda F.; Ernst, Susan; Dalton, Vanessa K.

    2012-01-01

    Objective: To examine human papillomavirus (HPV) vaccine intent and the effect of an educational intervention on vaccine uptake among female college students. Participants: Females aged 18 to 26 attending a university health service gynecology clinic (n = 256). Methods: Participants were randomized to receive either HPV-specific education with a…

  20. Human Papillomavirus Vaccine Intent and Uptake among Female College Students

    ERIC Educational Resources Information Center

    Patel, Divya A.; Zochowski, Melissa; Peterman, Stephanie; Dempsey, Amanda F.; Ernst, Susan; Dalton, Vanessa K.

    2012-01-01

    Objective: To examine human papillomavirus (HPV) vaccine intent and the effect of an educational intervention on vaccine uptake among female college students. Participants: Females aged 18 to 26 attending a university health service gynecology clinic (n = 256). Methods: Participants were randomized to receive either HPV-specific education with a…

  1. Intention of College Students to Receive the Human Papillomavirus Vaccine

    ERIC Educational Resources Information Center

    Richards, Keith

    2016-01-01

    Purpose: The purpose of this paper is to better understand what influences the intentions of college students to receive the human papillomavirus (HPV) vaccine. HPV is the most common sexually transmitted infection in the USA and cancers related to HPV are on the rise. Design/Methodology/Approach: A 2×2 experimental design was used to predict the…

  2. Development of a Human Papillomavirus Vaccination Intervention for Australian Adolescents

    ERIC Educational Resources Information Center

    Cooper, Spring C.; Davies, Cristyn; McBride, Kate; Blades, Joanna; Stoney, Tanya; Marshall, Helen; Skinner, S. Rachel

    2016-01-01

    Objective: Australia has implemented a nation-wide programme providing a human papillomavirus (HPV) vaccine to girls and boys through school-based programmes. Previous research has identified three distinct areas for attention: (1) lack of understanding about HPV and HPV vaccination, (2) young people's desire for involvement in decision-making…

  3. Pathobiology of human papillomaviruses in human immunodeficiency virus - Infected persons.

    PubMed

    Krishnamurti, Uma; Unger, Elizabeth R

    2017-07-01

    There is a complex interrelationship between human papillomaviruses (HPV) and human immunodeficiency viruses (HIV) that has been recognized from the start of the HIV epidemic. Cervical cancer was used as a surveillance indicator for acquired immunodeficiency syndrome (AIDS) before definitive identification of the viral etiology of either condition were known. Careful epidemiologic studies combined with clinical and laboratory measures of HPV, HPV-associated disease, and HIV have helped us understand many aspects of the relationship between these two virus groups; however, questions remain. The histopathology associated with HPV is identical in HIV-positive and negative patients though the lesions are more frequent, with higher frequency of multiple HPV types, and persistent in HIV infected individuals. In this review we will briefly explain the pathobiology of HPV in HIV-infected persons and the potential impact of secondary (screening) and primary (vaccination) prevention to reduce HPV-associated disease in those infected with HIV. Published by Elsevier Inc.

  4. Prevalence, Acquisition, and Clearance of Cervical Human Papillomavirus Infection among Women with Normal Cytology: Hawaii Human Papillomavirus Cohort Study

    PubMed Central

    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.

    2009-01-01

    Few natural history studies of cervical human papillomavirus (HPV) incidence and duration have been conducted among older women, especially from multiethnic populations. Viral and nonviral determinants of HPV acquisition and clearance were examined among 972 sexually active women, ages 18 to 85 years, recruited from clinics on Oahu, Hawaii, and followed for a mean duration of 15 months (range, 2–56 months). Interviews and cervical cell specimens for cytology and HPV DNA detection by PCR, using the PGMY09/PGMY11 primer system, were obtained at baseline and at 4-month intervals. The prevalence of cervical HPV infection was 25.6% at study entry. A total of 476 incident genotype-specific infections were observed during the follow-up period. The incidence of high-risk (HR) HPV types (9.26 per 1,000 woman-months) was similar to low-risk (LR) HPV types (8.24 per 1,000 woman-months). The most commonly acquired HR-HPV types were HPV-52, HPV-16, and HPV-31; and their incidence was increased significantly with a coexisting cervical HPV infection. Cervical HPV acquisition decreased with age, income, and long-term use of oral contraceptives and increased with number of sexual partners, use of hormonal creams, alcohol drinking, and condom use by a sexual partner. Cohort participants cleared 265 of the 476 incident infections during follow-up. LR-HPV infections cleared more rapidly than did HR-HPV infections (median, 180 days versus 224 days). Clearance times were enhanced among older women and women with multiple infections. Our data suggest several viral and nonviral determinants of cervical HPV acquisition and clearance that might be used in cervical cancer prevention programs. PMID:18974124

  5. 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

    Feller, Liviu; Wood, Neil H; Khammissa, Razia A G; Lemmer, Johan

    2010-07-15

    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.

  6. A study on the predictors of Korean male students' intention to receive human papillomavirus vaccination.

    PubMed

    Choi, Jeong Sil; Park, Seungmi

    2016-11-01

    The objective was to survey the current state of human papillomavirus (HPV) vaccination and the predictors of vaccination intention among Korean male students of high school (ages 15-19) and university (ages 17-27). Human papillomavirus is a sexually transmitted infectious agent causing uterine cervical, anal, and/or penile cancer and genital warts in males and females. Infection rate of human papillomavirus increases from the age when sexual intercourse first occurs. Therefore, motivation to receive human papillomavirus vaccination is needed to protect infection. Cross-sectional descriptive survey was performed only in male students. They are less aware of human papillomavirus than females, because human papillomavirus vaccination has been targeted on females for preventing cervical cancer in Korea. Data were collected using a self-reporting questionnaire for male high school and university students sampled from a city in Korea. Human papillomavirus vaccine-related knowledge, health beliefs, demographic, and sexual history information variables relating to intentions to vaccinate were assessed. The human papillomavirus vaccination rate was very low and the levels of knowledge and health beliefs were low. The significant predictors that raised the intention of human papillomavirus vaccination were a university student, experience of sexual intercourse and perceiving the benefits of human papillomavirus vaccination. To promote human papillomavirus vaccination, educational programming targeting males should include health beliefs and knowledge, emphasising that vaccination is important to prevent uterine cervical cancer and to role as a preventative measure against common male diseases. Male high school students should be included as a major target population for school human papillomavirus education programmes, as they are at the age of commencing sexual intercourse. In addition, public health policies including human papillomavirus vaccination in the national

  7. Maturation of the Human Papillomavirus 16 Capsid

    PubMed Central

    Cardone, Giovanni; Moyer, Adam L.; Cheng, Naiqian; Thompson, Cynthia D.; Dvoretzky, Israel; Lowy, Douglas R.; Schiller, John T.; Steven, Alasdair C.; Buck, Christopher B.

    2014-01-01

    ABSTRACT Papillomaviruses are a family of nonenveloped DNA viruses that infect the skin or mucosa of their vertebrate hosts. The viral life cycle is closely tied to the differentiation of infected keratinocytes. Papillomavirus virions are released into the environment through a process known as desquamation, in which keratinocytes lose structural integrity prior to being shed from the surface of the skin. During this process, virions are exposed to an increasingly oxidative environment, leading to their stabilization through the formation of disulfide cross-links between neighboring molecules of the major capsid protein, L1. We used time-lapse cryo-electron microscopy and image analysis to study the maturation of HPV16 capsids assembled in mammalian cells and exposed to an oxidizing environment after cell lysis. Initially, the virion is a loosely connected procapsid that, under in vitro conditions, condenses over several hours into the more familiar 60-nm-diameter papillomavirus capsid. In this process, the procapsid shrinks by ~5% in diameter, its pentameric capsomers change in structure (most markedly in the axial region), and the interaction surfaces between adjacent capsomers are consolidated. A C175S mutant that cannot achieve normal inter-L1 disulfide cross-links shows maturation-related shrinkage but does not achieve the fully condensed 60-nm form. Pseudoatomic modeling based on a 9-Å resolution reconstruction of fully mature capsids revealed C-terminal disulfide-stabilized “suspended bridges” that form intercapsomeric cross-links. The data suggest a model in which procapsids exist in a range of dynamic intermediates that can be locked into increasingly mature configurations by disulfide cross-linking, possibly through a Brownian ratchet mechanism. PMID:25096873

  8. Molecular characterization of the L1 gene of papillomaviruses in epithelial lesions of cats and comparative analysis with corresponding gene sequences of human and feline papillomaviruses.

    PubMed

    Anis, Eman A; O'Neill, Sarah H; Newkirk, Kim M; Brahmbhatt, Rupal A; Abd-Eldaim, Mohamed; Frank, Linda A; Kania, Stephen A

    2010-12-01

    To characterize the L1 gene of papillomaviruses detected in epithelial lesions of cats and to determine the relationship between those L1 gene nucleotide sequences and known L1 gene sequences of human and feline papillomaviruses. 10 tissue samples of epithelial lesions from 8 cats. DNA was extracted from tissue samples. Primers were designed to amplify the L1 gene of papillomaviruses. Amplicons of DNA were sequenced; nucleotide sequences were compared with known L1 gene nucleotide sequences of papillomaviruses and used for phylogenetic analysis. Tissue samples were obtained from lesions (diagnosed as dysplasia [n=1], squamous cell carcinoma in situ [3], or squamous cell carcinoma [6]) of the skin (9) and oral mucosa [1]. Two amplicons had 99% homology with the L1 gene nucleotide sequence of human papillomavirus type 38b subtype FA125. Another amplicon had 84% homology with the L1 gene nucleotide sequence of human papillomavirus type 80 and was considered to be a new type of papillomavirus. Phylogenetic tree analysis revealed that these 3 papillomaviruses were grouped into 2 clades that were not similar to the clades of Felis domesticus papillomavirus type 1 or F domesticus papillomavirus type 2 (FdPV2). The remaining 7 amplicons had 98% to 100% homology with the L1 gene nucleotide sequence of FdPV2. Phylogenetic tree analysis revealed that those 7 papillomaviruses were grouped nto a single clade with FdPV2. Results support the likelihood of transmission of papillomaviruses between humans and cats.

  9. Prevalence, distribution and correlates of endocervical human papillomavirus types in Brazilian women

    PubMed Central

    Lippman, S A; Sucupira, M C A; Jones, H E; Luppi, C G; Palefsky, J; van de Wijgert, J H H M; Oliveira, R L S; Diaz, R S

    2010-01-01

    Summary We determined the prevalence, distribution and correlates of human papillomavirus (HPV) types in 386 mixed-income, sexually active women in São Paulo, Brazil. Endocervical samples were tested for HPV DNA with L1 primers MY09 and MY11; negative and indeterminate samples were retested using GP 5+/6+ consensus primers. HPV was detected in 35% of all women; high-risk/probable high-risk types in 20%; low-risk types in 7%; and an indeterminate type in 10%. Twenty-five HPV types were found overall: 17 (probable) high-risk types and eight low-risk types. Approximately one-third (29%) of women with HPV infection were positive for type 16 or 18 and 36% were positive for types 6, 11, 16 or 18. The presence of (probable) high-risk HPV was associated with younger age, more lifetime sex partners and abnormal vaginal flora. Additional studies mapping the distribution of HPV types worldwide are necessary to prepare for vaccination programmes and direct future vaccine development. PMID:20089995

  10. Human Papillomavirus (HPV) Detection in Cytologic Specimens: Similarities and Differences of Available Methodology

    PubMed Central

    Tornillo, Luigi; Kind, André B.; Obermann, Ellen; Noppen, Christoph; Chaffard, Rosemarie; Wynne, Patricia; Grilli, Bruno; Foerster, Anja; Terracciano, Luigi M.; Hoeller, Sylvia

    2017-01-01

    Accumulating evidence regarding the causative role of human papillomavirus (HPV) in a wide range of malignant and nonmalignant diseases highlights the importance of HPV testing. This study describes and discusses the efficacy and characteristics of 4 well-established and commercially available tests. Here, 181 cytologic specimens from cervical smears were analyzed using the HPV SIGN PQ (Diatech) and the Linear Array (Roche) method. Discrepant results were further studied with the Real Time High-Risk HPV (Abbott) method and the INNO-LiPA (Fujirebio) method. Of 181 cytologic specimens, 61 (34%) showed discrepant results. High-risk HPV was not detected in 9 cases by HPV SIGN PQ, in 16 cases by Linear Array, in 10 cases by Real Time High-Risk HPV, and in 6 cases by INNO-LiPA, respectively. Lack of DNA detection or problems in interpreting the result were seen in 9 cases with HPV SIGN PQ, 8 cases with Linear Array, 3 cases with Real Time High-Risk HPV, and 3 cases with INNO-LiPA, respectively. This study indicates that the choice of HPV detection method has a substantial influence on the HPV risk classification of tested PAP smears and clinical follow-up decisions. PMID:26580098

  11. Molecular epidemiology of genital human papillomavirus and Chlamydia trachomatis among patients attending a genitourinary medicine clinic - will vaccines protect?

    PubMed

    Jalal, H; Stephen, H; Bibby, D F; Sonnex, C; Carne, C A

    2007-09-01

    High-risk subtypes of human papillomavirus (HPV) are the main causative agents of cervical cancer, for which Chlamydia trachomatis (CT) may sometimes be a co-factor. Vaccines have been developed against some subtypes of human papillomavirus and a vaccine against CT is in development. The objective of this study was to determine the prevalence of the subtypes of HPV and CT in genitourinary (GU) medicine clinic attenders. In total, 1000 consecutive patients attending the GU clinic participated in this anonymized point-prevalence study. Urethral swabs from 437 men and urethral plus cervical swabs as a single specimen from 563 women were tested for the subtypes of both organisms. Nested major outer membrane protein (MOMP) polymerase chain reaction detected CT chromosomal DNA in 44/437 (10%) of the men and 73/563 (13%) of the women. Genotypes E, F, and D were the most common. In all, 55/437 (13%) of men and 244/563 (43%) of women were infected with at least one high-risk HPV type. In conclusion, the new HPV vaccines, Gardasil and Cervarix, would have protected against 58% and 45%, respectively, of the high-risk subtypes found in women in this population. The rate of high-risk HPV infection (43%) found in women in this study raises concern.

  12. Prognostic significance of tumour progression and human papillomavirus in advanced tonsillar cancer classified as stage IVa.

    PubMed

    Park, E; Jung, K-Y; Kwon, S-Y; Woo, J-S; Cho, J-G; Park, M W; Kim, I S; Kim, S J; Baek, S-K

    2015-01-01

    To identify clinical factors that can explain the differences in treatment outcome, and examine the value of human papillomavirus infection as a prognostic biomarker in stage IVa tonsillar carcinomas. Fifty-nine patients with tonsillar carcinoma classified as stage IVa were retrospectively analysed for survival outcomes according to various clinical factors. Human papillomavirus infection was evaluated using a human papillomavirus DNA chip test and immunohistochemical staining for p16 and p53. Lower disease-free survival rates were associated with increasing local invasiveness and nodal status. Although human papillomavirus positivity and p16 expression was more common in locally advanced tonsillar carcinomas with advanced nodal status, the overall survival rate was better for patients with human papillomavirus positive, p16-positive tumours. The disease-free survival rate may differ according to local tumour invasiveness and nodal status, even for stage IVa tonsillar cancers. Human papillomavirus infection may be a useful biomarker for predicting treatment outcomes for stage VIa tumours.

  13. Evidence of recombination within human alpha-papillomavirus

    PubMed Central

    Angulo, Manuel; Carvajal-Rodríguez, Antonio

    2007-01-01

    Background Human papillomavirus (HPV) has a causal role in cervical cancer with almost half a million new cases occurring each year. Presence of the carcinogenic HPV is necessary for the development of the invasive carcinoma of the genital tract. Therefore, persistent infection with carcinogenic HPV causes virtually all cervical cancers. Some aspects of the molecular evolution of this virus, as the putative importance of recombination in its evolutionary history, are an opened current question. In addition, recombination could also be a significant issue nowadays since the frequency of co-infection with more than one HPV type is not a rare event and, thus, new recombinant types could be currently being generated. Results We have used human alpha-PV sequences from the public database at Los Alamos National Laboratory to report evidence that recombination may exist in this virus. A model-based population genetic approach was used to infer the recombination signal from the HPV DNA sequences grouped attending to phylogenetic and epidemiological information, as well as to clinical manifestations. Our results agree with recently published ones that use a different methodology to detect recombination associated to the gene L2. In addition, we have detected significant recombination signal in the genes E6, E7, L2 and L1 at different groups, and importantly within the high-risk type HPV16. The method used has recently been shown to be one of the most powerful and reliable procedures to detect the recombination signal. Conclusion We provide new support to the recent evidence of recombination in HPV. Additionally, we performed the recombination estimation assuming the best-fit model of nucleotide substitution and rate variation among sites, of the HPV DNA sequence sets. We found that the gene with recombination in most of the groups is L2 but the highest values were detected in L1 and E6. Gene E7 was recombinant only within the HPV16 type. The topic deserves further study

  14. Human papillomavirus in virgins and behaviour at risk.

    PubMed

    Frega, Antonio; Cenci, Maria; Stentella, Patrizia; Cipriano, Luca; De Ioris, Andrea; Alderisio, Mauro; Vecchione, Aldo

    2003-05-08

    Human papillomavirus (HPV) infection is one of the most common sexual transmitted diseases (STDs). We compared two groups of virgins with genital HPV lesions to evaluate the behaviour at risk in the transmission of HPV infection. Partners were also examined. HPV lesions were detected in 88 virgins, who have never had sexual intercourse. This can be due to vertical transmission, fomities and skin-to-skin contact. Many other hypothesis can be proposed to explain HPV genital infection, however, further studies are required.

  15. Human Papillomavirus-Related Oropharyngeal Cancer in Women.

    PubMed

    Scaffidi, Rose M; Gerhardt, Jill; Eisele, Cheryle

    2016-05-01

    The number of women diagnosed with oropharyngeal cancer related to the human papillomavirus (HPV) is increasing in the United States. Educating health care providers and women about the link between HPV and oropharyngeal cancers can aid in earlier diagnosis and treatment. This article discusses the etiology and clinical presentation of HPV-positive and HPV-negative oropharyngeal cancer, noting distinctions between the 2 types. Recommendations for screening and prevention are provided. © 2016 by the American College of Nurse-Midwives.

  16. Implication of human papillomavirus-66 in vulvar carcinoma: a case report.

    PubMed

    Kotsopoulos, Ioannis C; Tampakoudis, Georgios P; Evaggelinos, Dimitrios G; Nikolaidou, Anastasia I; Fytili, Panagiota A; Kartsiounis, Vasilios C; Gerasimidou, Domniki K

    2011-06-25

    Vulvar cancer in older women is seldom associated with human papillomavirus infection. We present the case of an 80-year-old Greek Caucasian woman with an undetermined obstetric and gynecologic history. The patient underwent radical vulvectomy and bilateral inguinal lymphadenectomy for a vulvar carcinoma. A human papillomavirus infection was suggested on the basis of histological and cytological examinations followed by human papillomavirus DNA typing, which revealed the presence of human papillomavirus-66. Even though human papillomavirus-16 and human papillomavirus-18 are most frequently implicated in the pathogenesis of vulvar carcinoma, human papillomavirus-66 can also be regarded as a causative factor. Suspicious lesions should be biopsied, and in the presence of carcinoma, vulvectomy with bilateral lymphadenectomy, if necessary, must be performed. Furthermore, polymerase chain reaction assay analysis with clinical arrays in cytological samples is an accurate test for the detection of a wide range of human papillomavirus genotypes and can be used to verify the infection and specify the human papillomavirus type implicated.

  17. Detection of human papillomavirus types 45 and 51 by type-specific polymerase chain reaction.

    PubMed

    Weyn, Christine; Boulenouar, Selma; Mathys, Vanessa; Vanhoolandt, Julie; Bernis, Aurore; Fontaine, Véronique

    2007-12-01

    Human papillomavirus (HPV) types 45 and 51 are both considered as high risk types for the development of human cervical cancer. To optimize the detection of these two types in clinical samples, HPV-45 and HPV-51 specific primers were designed to amplify respectively a 141bp and a 266bp fragment from the L1 gene by polymerase chain reaction (PCR). The sensitivity and the specificity of these two PCR reactions were determined using varying amounts of HPV DNA containing plasmids and negative and positive controls. Overall, the sensitivity for the HPV-45 plasmid DNA is 10fg, while for HPV-51 the sensitivity is 1fg. This is equivalent to approximately 100 and 10 HPV genome copies per PCR reaction, respectively.

  18. Human papillomavirus in the HIV-infected host: epidemiology and pathogenesis in the antiretroviral era.

    PubMed

    Brickman, Cristina; Palefsky, Joel M

    2015-03-01

    Human papillomavirus (HPV) infection is associated with essentially all cervical cancers, 80-90 % of anal cancers, and a high proportion of oropharyngeal, vaginal, penile, and vulvar cancers. Malignancy is preceded by the development of precancerous lesions termed high-grade squamous intraepithelial lesions (HSIL). Men and women with human immunodeficiency virus (HIV) infection are at high risk of HPV-related malignancies. The incidence of anal cancer in particular has markedly risen during the antiretroviral era due to the increased longevity of patients with HIV and the absence of anal malignancy screening programs. HIV infection may facilitate initial HPV infection by disrupting epithelial cell tight junctions. Once infection is established, HIV may promote HSIL development via the up-regulation of HPV oncogene expression and impairment of the immune response needed to clear the lesion. HIV-infected women should be screened for cervical HSIL and cancer, and HIV-infected men and women should be considered for anal screening programs.

  19. Comparative transforming potential of different human papillomaviruses associated with non-melanoma skin cancer

    SciTech Connect

    Massimi, Paola; Thomas, Miranda; Bouvard, Veronique; Ruberto, Irene; Campo, M. Saveria; Tommasino, Massimo; Banks, Lawrence

    2008-02-20

    It is well established that high-risk human papillomaviruses (HPVs) that infect mucosal epithelia are the causative agents of cervical cancer. In contrast, the association of cutaneo-tropic HPV types with the development of non-melanoma skin cancer (NMSC) is less well defined. In this study, we have analysed the in vitro transforming potential of various cutaneous HPV types. Using oncogene cooperation assays with activated ras, we have shown that diverse cutaneous types, including 12, 14, 15, 24, 36 and 49, have significant transforming potential. Interestingly, most of this activity appears to be encoded by the E6 gene product. In contrast, the common HPV-10 exhibits no significant transforming potential in these assays. This difference may be a reflection of different patterns of cellular localization, with transforming E6s being nuclear and non-transforming being cytoplasmic. These results provide molecular support for a role of these viruses in the development of certain human malignancies.

  20. [Oncogenic potential of papillomaviruses].

    PubMed

    Váňová, B; Golais, F

    2013-01-01

    Papillomaviruses belong to a group of viruses with double-stranded DNA (dsDNA). These viruses are believed to induce benign as well as malignant tumour growth. Thanks to professor zur Hausen, the connection between the infection by human papillomaviruses (HPV) and cervix cancer was described in detail a few years ago. However, there exist certain types of HPV viruses, in which no association with malignancies was ever demonstrated. Hence, we can divide HPV into "high-risk" (HR) and "low-risk" (LR) group. Our work describes the life cycle of HPV, molecular mechanisms of oncogenesis and aims to compare HR HPV and LR HPV within these terms.

  1. Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia.

    PubMed

    Egawa, Nagayasu; Egawa, Kiyofumi; Griffin, Heather; Doorbar, John

    2015-07-16

    Papillomaviruses have evolved over many millions of years to propagate themselves at specific epithelial niches in a r