Clinical, subclinical, and latent human papillomavirus (HPV) infections are distinguished from HPV-associated neoplasia. Besides HPV additional cofactors are necessary to transform HPV infected tissue to intraepithelial or invasive neoplasia. Risk factors for the presence of HPV are high number of sexual partners, early cohabitarche, young age at first delivery, suppression and alteration of immune status, young age and hormonal influences. While the fact of a high number of sexual partners exclusively increases the risk of HPV infection, it is not known whether the other factors lead to either an increased risk for HPV infection and/or to HPV-associated neoplasia. Subclinical and latent genital HPV infections are highly prevalent. The prevalence rate depends on the sensitivity of the HPV detection system used, on age and sexual activity of the population screened, and on the number of subsequent examinations performed for each subject. Sexual transmission is the main pathway for genital HPV's, however, vertical, peripartal, and oral transmission are also possible. Seroreactivity against genital HPV may be due to an active infection or the result of contact with HPV earlier in life. Antibodies against the HPV 16 E7 protein indicate an increased risk for cervical cancer. Compared with humoral response cellular immune response is probably more important for regression of genital HPV infection: impaired cellular response is characterized by depletion of T helper/inducer cells and/or Langerhans cells and impaired function of natural killer cells and/or the infected keratinocyte. In condylomata replication and transcription of viral nucleic acids and antigen production coincide with cellular differentiation. However, the interaction between HPV and the keratinocyte on a molecular level in subclinical and latent disease is not well understood. Regression or persistence of subclinical and latent genital HPV infections as observed in longitudinal investigations show a constant come-and-go of HPV presence. Subclinical or latent cervical infections with high-risk HPV types (such as HPV 16 and 18) have an increased risk for the development of HPV-associated neoplasia.
Thirty-nine patients with condylomas (12 women and 27 men) attending a dermatology clinic were tested for genital human papillomavirus (HPV) DNA and for seroprevalence to HPV type 6 (HPV6) L1 virus-like particles. The L1 consensus PCR system (with primers MY09 and MY11) was used to determine the presence and types of HPV in sample specimens. All 37 (100%) patients with sufficient DNA specimens were positive for HPV DNA, and 35 (94%) had HPV6 DNA detected at the wart site. Three patients (8%) had HPV11 detected at the wart site, and one patient had both HPV6 and -11 detected at the wart site. Thirteen additional HPV types were detected among the patients; the most frequent were HPV54 (8%) and HPV58 (8%). Baculovirus-expressed HPV6 L1 virus-like particles were used in enzyme-linked immunosorbent assays to determine seroprevalence among the patients with warts. Seronegativity was defined by a control group of 21 women who were consistently PCR negative for HPV DNA. Seroprevalence was also determined for reference groups that included cytologically normal women who had detectable DNA from either HPV6 or HPV16 and women with HPV16-associated cervical intraepithelial neoplasia. Among the asymptomatic women with HPV6, only 2 of 9 (22%) were seropositive, compared with 12 of 12 (100%) female patients with warts. A similar trend in increased HPV6 seropositivity with increased grade of disease was found with the HPV16 DNA-positive women, whose seroprevalence increased from 1 in 11 (9%) in cytologically normal women to 6 in 15 (40%) among women with cervical intraepithelial neoplasia 1 or 3. However, only 4 of 25 (16%) male patients were seropositive.(ABSTRACT TRUNCATED AT 250 WORDS)
Greer, C E; Wheeler, C M; Ladner, M B; Beutner, K; Coyne, M Y; Liang, H; Langenberg, A; Yen, T S; Ralston, R
Genital Human Papillomavirus (HPV) At least 50% of sexually active women and men will get it. Most will not ... possible effects of HPV. W hat is genital human papillomavirus (HPV)? HPV is a common virus. There ...
Human papillomavirus type 16 (HPV16) early proteins E6 and E7 have been implicated in maintenance of the malignant phenotype in cervical cancer. Transforming growth factors beta one and two (TGF betas 1 and 2), polypeptides that regulate cellular growth and differentiation, reversibly inhibited expression of the HPV16 E6 and E7 genes in several immortal genital epithelial cell lines. Loss of E6 and E7 protein expression followed a dramatic time- and dose-dependent decrease in E6 and E7 RNA levels and was accompanied by cessation of cell proliferation. TGF betas 1 and 2 inhibited HPV16 RNA expression at the transcriptional level; inhibition was dependent upon ongoing protein synthesis. TGF betas 1 and 2 also induced a six- to sevenfold increase in TGF beta 1 RNA. Cells became partially resistant to the inhibitory effects of TGF beta 1 on cell growth and HPV early gene expression after prolonged cultivation in vitro or after malignant transformation. Thus, TGF beta 1 may function as an autocrine regulator of HPV gene expression in infected genital epithelial cells. Images
Woodworth, C D; Notario, V; DiPaolo, J A
Background We investigated the role of infection with genital and cutaneous human papillomavirus types (HPV) in the aetiology of ocular surface squamous neoplasia (which includes both conjunctival intraepithelial neoplasia (CIN) and carcinoma) using data and biological material collected as part of a case-control study in Uganda. Results Among 81 cases, the prevalence of genital and cutaneous HPV types in tumour tissue did not differ significantly by histological grade of the lesion. The prevalence of genital HPV types did not differ significantly between cases and controls (both 38%; Odds ratio [OR] 1.0, 95% confidence interval [CI] 0.4–2.7, p = 1.0). The prevalence of cutaneous HPV types was 22% (18/81) among cases and 3% (1/29) among controls (OR 8.0, 95% CI 1.0–169, p = 0.04). Conclusion We find no evidence of an association between genital HPV types and ocular surface squamous neoplasia. The prevalence of cutaneous HPV was significantly higher among cases as compared to controls. Although consistent with results from two other case-control studies, the relatively low prevalence of cutaneous HPV types among cases (which does not differ by histological grade of tumour) indicates that there remains considerable uncertainty about a role for cutaneous HPV in the aetiology of this tumour.
de Koning, Maurits NC; Waddell, Keith; Magyezi, Joseph; Purdie, Karin; Proby, Charlotte; Harwood, Catherine; Lucas, Sebastian; Downing, Robert; Quint, Wim GV; Newton, Robert
Background.?Few studies have assessed genital human papillomavirus (HPV) concordance and factors associated with concordance among asymptomatic heterosexual couples. Methods.?Genotyping for HPV was conducted with male and female sex partners aged 18–70 years from Tampa, Florida. Eligibility included no history of HPV-associated disease. Type-specific positive concordance (partners with ?1 genotype in common) and negative concordance (neither partner had HPV) were assessed for 88 couples. Factors associated with concordance were assessed with Fisher exact tests and tests for trend. Results.?Couples reported engaging in sexual intercourse for a median of 1.7 years (range, 0.1–49 years), and 75% reported being in the same monogamous relationship for the past 6 months. Almost 1 in 4 couples had type-specific positive concordance, and 35% had negative concordance for all types tested, for a total concordance of 59%. Concordance was not associated with monogamy. Type-specific positive concordance was associated with an increasing difference in partners’ lifetime number of sex partners and inversely associated with an increasing difference in age. Negative concordance was inversely associated with both the couple's sum of lifetime number of sex partners and the difference in the partners’ lifetime number of sex partners. Conclusions.?Genital HPV concordance was common. Viral infectiousness and number of sex partners may help explain concordance among heterosexual partners.
Nyitray, Alan G.; Menezes, Lynette; Lu, Beibei; Lin, Hui-Yi; Smith, Dan'elle; Abrahamsen, Martha; Papenfuss, Mary; Gage, Christine; Giuliano, Anna R.
Anogenital infections caused by Human papillomavirus (HPV) are the most frequently diagnosed sexually transmitted infections of viral origin and up to 150 HPV DNA types have been recognized so far. Anogenital warts (condylomata acuminata) are the most common lesions presented in men, however, during the last decade the other HPV-associated exaggerated lesions such as condylomata plana, penile, scrotal, and anal intraepithelial neoplasias, as well as the penile, urine bladder and prostate cancer have been studied somewhat more extensively. The clinical variations might range from clinically invisible, asymptomatic lesions to the bizarre forms of giant condyloma of Buschke-Löwenstein type, including Bowenoid papulosis, Mb. Bowen, different kinds of eryhtroplasia both in men and women and a large spectrum of HPV-induced dermatovenereological entities in genital region including high-grade intraepithelial genital neoplasias, such as penile, anal, scrotal, vulvar, vaginal etc. (thus not only cervical), and, last but not least - the anogenital warts. A prophylactic vaccine that targets these types should thus substantially reduce the burden of HPV-associated clinical diseases. Ultimately, within the spectrum of therapeutic options for condylomata, no method is really superior to others; recurrences occurred in 30-70% of cases. We definitely need the HPV vaccination programme to eliminate one of the oldest and up to now unsolved problems of the mankind. Since HPV is transmitted by sexual intercourse, treatment of both partners is necessary in order to eliminate the virus from the population. Approaches to this include prophylactic vaccines such as quadrivalent HPV vaccine for both men and women. PMID:21258302
Skerlev, Mihael; Ljubojevic, Suzana
Objective: Cervical cancer is a leading cause of cancer mortality in South Africa. However, little is known about oral human papillomavirus (HPV) infection in high human immunodeficiency virus (HIV) seroprevalence settings. Method: Thirty-four adult heterosexual couples attending an HIV testing center in Soweto, South Africa were enrolled. Each participant provided an oral rinse sample and genital swab, which were tested for 37 types of HPV DNA, and completed a risk behavior survey. Results: Median age was 31?years and 9% (3/34) of men and 29% (10/34) of women enrolled tested HIV-positive; median CD4 count was 437?cells/mm(3). Oral HPV prevalence was similar in women and men (12 vs. 18%, p?=?0.48), and was non-significantly higher in HIV-infected vs. HIV-uninfected (23 vs. 13%, p?=?0.34) subjects. Most men (82%) and women (84%) reported ever performing oral sex. Median number of lifetime sexual partners was "2-5" while median number of lifetime oral sex partners was 1. Oncogenic HPV subtypes were detected in 4% of oral, 26% of penile, and 74% of vaginal samples, including HPV16 in 1, 12, and 21% of these samples respectively. Genital HPV prevalence was significantly higher than oral HPV prevalence (75 vs. 15%, p???0.001). Thirty-five percent of couples (12/34) had at least one type-specific concordant vaginal-penile HPV infection but only one of nine couples with oral HPV had concordant oral-oral infection. However, 67% (4/6) of men and 25% (1/4) of women with oral HPV infection had partners with concordant genital HPV infection. Implications and Impact: Oral-oral HPV concordance between couples is low, but oral-genital and genital-genital HPV concordance is higher, including concordance of male oral HPV infection with their partners' vaginal HPV infection. This data is consistent with possible transmission of vaginal HPV infection to the oral cavity of sexual partners performing oral sex. PMID:24377087
Vogt, Samantha L; Gravitt, Patti E; Martinson, Neil A; Hoffmann, Jennifer; D'Souza, Gypsyamber
Objectives: Genital infection with certain types of human papillomavirus (HPV) is the most important risk factor for cervical cancer. The male sexual partner is supposed to be the vector of the infection. However, the knowledge of risk factors for genital HPV DNA in men is limited. The objective of this paper is to study the risk factors for HPV infection
E I Svare; S K Kjaer
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The role of human papillomaviruses (HPVs) in the development of genital neoplasias has been well documented1-5. The genomes of two HPV types, HPV16 and HPV18, have been found to be associated with about 70% of invasive carcinomas of the uterine cervix2,4,6. As, under non-stringent hybridization conditions, HPV DNA sequences have been detected in about 90% of cervical carcinomas4,6, it seems
Sylvie Beaudenon; Dina Kremsdorf; Odile Croissant; Stefania Jablonska; Simon Wain-Hobson; Gérard Orth
Introduction: Genital Human Papillomavirus (HPV) infection is the most commonly occurring sexually transmitted viral infection in humans. HPV is a wide family of DNA viruses, which may cause benign skin and mucosal tumors (genital, anal or oral warts), intraepithelial neoplasias and\\/or malignant cancers in different organs. Women are more susceptible to the oncogenic effect of HPVs, mostly at the genital
Alessandra Graziottin; Audrey Serafini
More than 30 HPV types can infect the genital tract. Viral infection can be present in clinical, subclinical or latent form. A visible genital form of HPV infection are genital warts, which are commonly caused by HPV types 6 and 11, and appear on the vulva, cervix, vagina, urethra and anus. Oncogenic HPV types 16, 18, 31, 33 and 35 are also found in genital warts and are associated with vulval (VII), cervical (CIN) and anal (AIN) intraepithelial neoplasia. The general prevalence of HPV infection in the form of visible genital warts estimates to about 1% of sexually active adults. Approximately 15% of the infected group / of all adults have a subclinical or latent infection and at least 80% had been infected with one or more genital HPV types at some point in their lives. The highest rate of frequency of infections occurs in the group of adults, aged from 18 to 28. Over the last twenty years figures have shown a constant growth of the infection rate, which also includes pregnant women. Genital warts can proliferate during pregnancy due to altered immunity and increased blood supply. Cryotherapy, electrocautery, laser therapy, surgery or trichloroacetic acid may be used to remove the warts. In the paper a case report on genital warts associated with HPV infection during II and III trimester of pregnancy and analysis of treatment options has been presented. PMID:18306923
Rozmus-Warcholi?ska, Wioletta; Loch, Tomasz; Czuba, Bartosz; Mazurek, Urszula; Mucha, Jan; Dworak, Dariusz; Sodowski, Krzysztof
Human papillomavirus (HPV) infections are associated with sexual behavior. Changes in the sexual habits of couples and their impact on male genital and oral HPV infections were determined during 7 years of follow-up (FU). At baseline and 7 years FU, urethral, semen/penile, and oral samples were collected from 46 men and cervical and oral samples of their spouses for HPV DNA detection. Demographic data and risk factors of spouses were recorded by questionnaire at both time points and analyzed for concordance. HPV genotyping was done with the Multimetrix® kit. At baseline, 29.5 % of the male genital and 11 % of their oral samples tested positive. Incident genital HPV infection was found in 23 % and oral infection in 10.9 % of men. Genotype-specific persistence was detected in one man (HPV53) in genital samples. Moderate to almost perfect concordance of changes in sexual habits during FU among spouses were found. Changing partners [p?=?0.028; odds ratio (OR)?=?15; 95 % confidence interval (CI) 1.355-166.054] and marital status (p?=?0.001; 95 % CI 0.000-0.002) increased the risk of incident genital HPV infections. The overall outcome of genital HPV disease in men was linked to the frequency of sexual intercourse (p?=?0.023; 95 % CI 0.019-0.026) and changes in marital status (p?=?0.022; 95 % CI 0.019-0.026), while oral HPV infections were associated with the number of sexual partners (p?=?0.047; 95 % CI 0.041-0.052). Taken together, asymptomatic genital HPV infections among the men were common. The risk of incident genital HPV infections increased among men reporting a change of sexual partner during FU, implicating that a stable marital relationship protects against oral and genital HPV infection. PMID:24504632
Kero, K M; Rautava, J; Syrjänen, K; Kortekangas-Savolainen, O; Grenman, S; Syrjänen, S
Human papilloma virus infection is the most frequent sexually transmitted disease. HPV infections are connected with different diseases such as benign warts, condylomata acuminata, malignant cervical, vulvar, vaginal, penile and anal carcinoma. Peniscopy with HPV detection is a specific diagnostic method for diagnosis of subclinical HPV genital infection in asymptomatic men. Taking the samples for HPV detection from asymptomatic men with curette is more qualitative way of getting enough samples then taking swab with wooden stick or (tongue) depressor. Early diagnosis and treatment of HPV infections in men is of potential benefit because their eradication can reduce the viral reservoir and as the result of that the incidence of CIN, carcinoma in situ and invasive cervical carcinoma can be reduced. For the correct diagnosis and for choosing the adequate therapeutical technique, we suggest diagnostic-therapeutic guidelines for HPV genital infection in men. PMID:20030291
Ljubojevi?, Suzana; Lipozenci?, Jasna; Skerlev, Mihael; Zele-Starcevi?, Lidija; Ljubojevi?, Nikola; Babi?, Damir; Grubisi?, Goran; Juki?, Stanko
Human papillomaviruses (HPV) may cause sexually transmitted disease. High-risk types of HPV are involved in the development of cervical cell dysplasia, whereas low-risk types may cause genital condyloma. Despite the association between HPV and cancer, donor sperm need not be tested for HPV according to European regulations. Consequently, the potential health risk of HPV transmission by donor bank sperm has not been elucidated, nor is it known how HPV is associated with sperm. The presence of 35 types of HPV was examined on DNA from semen samples of 188 Danish sperm donors using a sensitive HPV array. To examine whether HPV was associated with the sperm, in situ hybridization were performed with HPV-6, HPV-16 and -18, and HPV-31-specific probes. The prevalence of HPV-positive sperm donors was 16.0% and in 66.7% of these individuals high-risk types of HPV were detected. In 5.3% of sperm donors, two or more HPV types were detected. Among all identified HPV types, 61.9% were high-risk types. In situ hybridization experiments identified HPV genomes particularly protruding from the equatorial segment and the tail of the sperm. Semen samples from more than one in seven healthy Danish donors contain HPV, most of them of high-risk types binding to the equatorial segment of the sperm cell. Most HPV-positive sperm showed decreased staining with DAPI, indicative of reduced content of DNA. Our data demonstrate that oncogenic HPV types are frequent in men.
Kaspersen, Maja D.; Larsen, Peter B.; Ingerslev, Hans Jakob; Fedder, Jens; Petersen, Gert Bruun; Bonde, Jesper; Hollsberg, Per
Cervical cancer is an important public health problem worldwide, and especially in developing countries. The link between cervical cancer and oncogenic human papillomavirus (HPV) infection has been clearly established. Furthermore, non-oncogenic HPV are responsible for the majority of genital warts. Two prophylactic HPV vaccines are available, which have the potential of considerably reducing HPV-related morbidity and mortality. Both vaccines are based on virus-like particles of the L1 capsid protein, and are highly efficacious and immunogenic if given before exposure to HPV, i.e. to adolescent girls between 9 and 13 years of age in a three-dose schedule. This review describes the immunology of natural HPV infections and the immune response evoked through vaccination. The current duration of protection is 8.4 years with the bivalent vaccine (HPV16/18) and 5 years with the quadrivalent vaccine (HPV6/11/16/18). Research is on-going to evaluate the efficacy of the current vaccines in a two-dose schedule, as compared to the recommended three-dose schedule. To increase the protection, the development and testing of a nine-valent prophylactic HPV vaccine (HPV6/11/16/18/31/33/45/52/58) is being undertaken. Research is also directed towards therapeutic vaccines and the development of a prophylactic L2 vaccine. PMID:24606637
Dochez, Carine; Bogers, Johannes J; Verhelst, Rita; Rees, Helen
This chapter provides an overview of the epidemiology of human papillomavirus (HPV) infection, with a focus on the dynamics of sexual transmission. We explore concepts related to the spread of sexually transmitted infections, including population prevalence, duration of infectivity, patterns of sexual contacts, and transmissibility, including modifiers of susceptibility and infectivity. HPV prevalence and incidence are high in most studies,
Ann N. Burchell; Rachel L. Winer; Silvia de Sanjosé; Eduardo L. Franco
Oncogenic HPVs have been found frequently integrated into human genome of invasive cancers and chromosomal localization has been extensively investigated in cervical carcinoma. Few studies have analyzed the HPV integration loci in other genital cancers. We have characterized the integration sites of HPV16 in invasive penile carcinoma by means of Alu-HPV-based PCR. Nucleotide sequence analysis of viral-human DNA junctions showed that HPV integration occurred in one case within the chromosome 8q21.3 region, in which the FAM92A1 gene is mapped, and in the second case inside the chromosome 16p13.3, within the intronic region of TRAP1 gene. These results confirm previous observations, summarized in a systematic review of the literature, on the HPV integration events in gene loci relevant to cancer pathogenesis. PMID:22451136
Annunziata, Clorinda; Buonaguro, Luigi; Buonaguro, Franco M; Tornesello, Maria Lina
Genital infection with high-risk human papillomavirus (HR HPV) associates with increased risk of developing precancerous lesions, such as cervical intraepithelial neoplasia (CIN). The objective of this pilot study conducted in north-east Croatia was to determine the prevalence of HPV genital infection in women with abnormal cervical cytology and to determine its association with their age and HPV genotype(s). From March 2009 to December 2011, cervical swabs from 100 women were analysed for HR HPV infection (AMPLICOR HPV Test, Roche Diagnostics) and genotyped for high risk (HR), intermediate (IR) and low risk (LR) HPVs (Linear Array HPV Genotyping Test, Roche Diagnostics). The most prevalent HR genotypes in women with CIN were HPV 16 (27.6%), HPV 31 (11.8%), HPV 51 and HPV 52 (10.2% each). The most prevalent IR genotypes were HPV 66 (30%) and HPV 62 (23.3%). The most prevalent LR genotype was HPV 6 (20.3%). Women between 21 and 25 years of age showed the highest rate of HPV infection (44.2%). Moreover, women younger than 35 years showed a significant association (p < 0.01) and positive correlation (r = 0.67; p < 0.05) between HR HPV infection and CIN stages 1 and 2. Multiple HPV infections were found in almost half of the women. This is the first study that analysed the prevalence of genital infection with HR/IR/LR HPVs in women with CIN from north-east Croatia. Despite the preliminary nature of this pilot study, the lower prevalence of some HR HPVs (HPV18) and the higher prevalence of other HR HPVs (HPVs 51, 52 and 31) may imply the necessity for the development of more targeted anti-HPV vaccines or other strategies for more efficient protection against oncogenic HPV infection in women from our region. PMID:24611331
Roksandi?-Krizan, Ivana; Bosnjak, Zinka; Peri?, Magdalena; Durkin, Ivona; Atali?, Vlasta Zuji?; Vukovi?, Dubravka
Investigation of HPV infection in men remains important due to its association with genital warts and anorectal cancer, as well as to the role men play in HPV transmission to their female sexual partners. Asymptomatic men (n?=?43), whose sexual partners had presented cervical HPV infection, were enrolled in this study. Among the 43 men, 23 had their female partner included and tested for HPV-DNA, totaling 23 couples. HPV-DNA was detected by PCR. Type specific PCR to detect HPV 16, 18, 31, 33, 45 and 6/11 was performed. At least one type of HPV was detected in 86.0% (37/43) of the male patients and more than one HPV type was identified in 39.5% (17/43) of the samples, including high and low risk HPV. HPV-16 proved to be the most prevalent viral type in both male and female samples. Concordance of at least one viral type was observed in 56.5% (13/23) of the couples. Among couples that have shown concordance of viral types, 84.6% (11/13) of the men had the same high risk viral type presented by the female sexual partner. These data suggest that HPV infected men is an important reservoir, contributing to a higher transmission to women and maintenance of infection, and consequently, a higher risk of developing cervical cancer. HPV vaccination in men will protect not only them but will also have implications for their sexual partners.
Rocha, Maria Gabrielle de Lima; Faria, Fabio Lopes; Goncalves, Leonor; Souza, Maria do Carmo M.; Fernandes, Paula Avila; Fernandes, Ana Paula
Background HPV burden is a predictor for high-grade cervical intraepithelial neoplasia and cancer. The natural history of HPV load in young women being recently exposed to HPV is described in this paper. Methods A total of 636 female university students were followed for 2 years. Cervical specimens with HPV-16, -18, -31, or -45 DNA by consensus PCR were further evaluated with type-specific and ?-globin real-time PCR assays. Proportional hazards regression was used to estimate hazard ratios (HR) of infection clearance. Generalized estimating equations assessed whether HPV loads was predictive of HPV infection at the subsequent visit. Results HPV loads were consistently higher among women <25 years old, and those who had multiple sex partners, multiple HPV type infections and smokers. HPV-16 integration was encountered only in one sample. Infection clearance was faster among women at lower tertiles of HPV-16 (HR = 2.8, 95%CI: 1.0-8.1), HPV-18 (HR = 3.5, 95%CI: 1.1-11.2) or combined (HR = 2.4, 95%CI: 1.8-6.2) DNA loads. The relationship between HPV-16 and HPV-18 DNA loads and infection clearance followed a clear dose-response pattern, after adjusting for age and number of sexual partners. GEE Odds Ratios for HPV persistence of the middle and upper tertiles relative to the lower tertile were 2.7 and 3.0 for HPV-16 and 3.8 and 39.1 for HPV-18, respectively. There was no association between HPV-31 or -45 DNA loads and persistence. Conclusions The association between HPV load and persistence is not uniform across high-risk genital genotypes. HPV-16 integration was only rarely demonstrated in young women.
Background Studies on HPV infection in pregnant women and HPV transmission to the child have yielded inconsistent results. Methods To estimate mother-to-child HPV transmission we carried out a prospective cohort study that included 66 HPV-positive and 77 HPV-negative pregnant women and their offspring attending a maternity hospital in Barcelona. To estimate HPV prevalence and genotype distribution in pregnancy we also carried out a related screening survey of cervical HPV-DNA detection among 828 pregnant women. Cervical cells from the mother were collected at pregnancy (mean of 31 weeks) and at the 6-week post-partum visit. Exfoliated cells from the mouth and external genitalia of the infants were collected around birth, at the 6-week post-partum visit, and around 3, 6, 12, and 24 months of age. All samples were tested for HPV using PCR. Associations between potential determinants of HPV infection in pregnant women and of HPV positivity in infants were also explored by logistic regression modelling. Results Overall cervical HPV-DNA detection in pregnant women recruited in the HPV screening survey was 6.5% (54/828). Sexual behavior-related variables, previous histories of genital warts or sexually transmitted infections, and presence of cytological abnormalities were statistically significantly and positively associated with HPV DNA detection in pregnant women recruited in the cohort. At 418 infant visits and a mean follow-up time of 14 months, 19.7% of infants born to HPV-positive mothers and 16.9% of those born to HPV-negative mothers tested HPV positive at some point during infants' follow-up. The most frequently detected genotype both in infants and mothers was HPV-16, after excluding untyped HPV infections. We found a strong and statistically significant association between mother's and child's HPV status at the 6-week post-partum visit. Thus, children of mothers' who were HPV-positive at the post-partum visit were about 5 times more likely to test HPV-positive than children of corresponding HPV-negative mothers (p = 0.02). Conclusion This study confirms that the risk of vertical transmission of HPV genotypes is relatively low. HPV persistence in infants is a rare event. These data also indicate that vertical transmission may not be the sole source of HPV infections in infants and provides partial evidence for horizontal mother-to-child HPV transmission.
Functional disturbance of p53 tumor suppressor protein contributes to uncontrolled cell growth. Human papillomavirus (HPV) E6 oncoproteins bind to wild-type p53 and abrogate its function. Our objective was to elucidate the relation of aberrant p53 protein expression to HPV DNA and cellular atypia in male genital warts and premalignant lesions. Immunohistochemically detectable p53 protein expression was studied in 35 male anogenital warts with low-level or no keratinocyte atypia (histologically confirmed condylomata acuminata), in 25 lesions with bowenoid papulosis (BP; carcinoma in situ) histology, and in 10 non-condyloma lesions using immunostaining with three established antibodies recognizing full-length wild-type accumulated p53 protein, or its conformational mutants. HPV DNA specific for HPV 6/11, 16/18, or 31/33/35 was identified by in situ hybridization or by polymerase chain reaction (PCR) - based amplification. Both nuclear and cytoplasmic keratinocyte immunostaining for p53 protein was detected in 41% of condylomata with no keratinocyte atypia and in 42% of condylomata with slight nuclear atypia or with bowenoid papulosis histology. No association of aberrant p53 expression with any specific HPV type or with HPV DNA was observed. Normal skin and some other penile dermatoses were negative for p53 immunostaining. In the follow-up biopsies of 16 BP patients, treated with CO2 laser, recurrence of atypia was seen exclusively in lesions initially positive for both HPV DNA and p53 protein. Our results show that a few cells in male genital warts even with no cellular atypia may express abnormally sequestered or loss-of-function p53 protein, and that concomitant presence of any type of HPV DNA is associated with recurrencies or progression of premalignant changes. PMID:7653176
Ranki, A; Lassus, J; Niemi, K M
Although HPV16 has been strongly implicated in oropharyngeal carcinogenesis, the role of other high-risk HPV types in the etiology of head and neck cancer remains unclear. To date, few data exist addressing the nature of the association between antibodies to oncogenic proteins of non-HPV16 HPVs in relation to head and neck cancer. We examined the relationship between multiple HPV types (HPV6, 11, 16, 18, 31, 33, 45, 52, 58) and head and neck squamous cell carcinoma (HNSCC) in a large population-based case-control study (1069 cases and 1107 controls). Serological measures for HPV types included antibodies to L1, E6 and/or E7. In a secondary analysis, we excluded HPV16 seropositive subjects to examine independent associations with other high-risk HPVs. All analyses were adjusted for age, race, sex, education, smoking and alcohol consumption. Statistically significant associations were observed for HPV16, 18, 33 and 52 and risk of HNSCC after mutually adjusting for HPV types. Among HPV16 seronegative subjects, elevated risks of HNSCC were observed for HPV18 E6 (OR?=?4.19, 95% CI?=?1.26-14.0), HPV33 E6 (OR?=?7.96, 95% CI?=?1.56-40.5) and HPV52 E7 (OR?=?3.40, 95% CI?=?1.16-9.99). When examined by tumor type, associations with HPV18 and HPV33 remained statistically significant for oropharyngeal cancer, and HPV52 was associated with oral cancer. In addition, magnitude of associations for HNSCC increased markedly with increasing number of seropositive high-risk HPV infections. High-risk HPV types, other than HPV16, are likely to be involved in the etiology of HNSCC. PMID:24615247
Michaud, Dominique S; Langevin, Scott M; Eliot, Melissa; Nelson, Heather H; Pawlita, Michael; McClean, Michael D; Kelsey, Karl T
Background An epidemic of human papillomavirus (HPV)-related oropharyngeal squamous cell cancer (OPSCC) has been reported worldwide largely due to oral infection with HPV type-16, which is responsible for approximately 90% of HPV-positive cases. The purpose of this study was to determine the rate of HPV-positive oropharyngeal cancer in Southwestern Ontario, Canada. Methods A retrospective search identified ninety-five patients diagnosed with OPSCC. Pre-treatment biopsy specimens were tested for p16 expression using immunohistochemistry and for HPV-16, HPV-18 and other high-risk subtypes, including 31,33,35,39,45,51,52,56,58,59,67,68, by real-time qPCR. Results Fifty-nine tumours (62%) were positive for p16 expression and fifty (53%) were positive for known high-risk HPV types. Of the latter, 45 tumors (90%) were identified as HPV-16 positive, and five tumors (10%) were positive for other high-risk HPV types (HPV-18 (2), HPV-67 (2), HPV-33 (1)). HPV status by qPCR and p16 expression were extremely tightly correlated (p?0.001, Fishers exact test). Patients with HPV-positive tumors had improved 3-year overall (OS) and disease-free survival (DFS) compared to patients with HPV-negative tumors (90% vs 65%, p?=?0.001; and 85% vs 49%, p?=?0.005; respectively). HPV-16 related OPSCC presented with cervical metastases more frequently than other high-risk HPV types (p?=?0.005) and poorer disease-free survival was observed, although this was not statistically significant. Conclusion HPV-16 infection is responsible for a significant proportion of OPSCC in Southwestern Ontario. Other high-risk subtypes are responsible for a smaller subset of OPSCC that present less frequently with cervical metastases and may have a different prognosis.
Genital human papillomaviruses (HPV) represent the most common sexually transmitted agents and are classified into low or high risk by their propensity to cause genital warts or cervical cancer, respectively. Topical microbicides against HPV may be a useful adjunct to the newly licensed HPV vaccine. A main objective in the development of novel microbicides is to block HPV entry into
David Lembo; Manuela Donalisio; Marco Rusnati; Antonella Bugatti; Maura Cornaglia; Paola Cappello; Mirella Giovarelli; Pasqua Oreste; Santo Landolfo
Human papillomaviruses (HPV) of the genera alpha, mu, and nu induce benign tumors of the cutaneous epithelia that constitute a significant burden for immunocompromised adults. Currently, no gold standard for genotyping of these HPV types exists. In this study, we describe the prevalence of genus alpha, mu, and nu HPV types in cutaneous warts. We developed a novel multiplex HPV genotyping assay, BSwart-PCR/MPG (BSwart), to type sensitively and specifically 19 cutaneous HPV types frequently found in warts. BSwart-PCR/MPG is based on a multiplex PCR using broad-spectrum primers and subsequent multiplex hybridization to type-specific probes coupled to Luminex beads. In a first application comprising 100 cutaneous warts, the assay was compared to another, recently described genotyping assay, the HSL-PCR/MPG. When a 10-fold dilution series was used, the detection limit was between 10 and 100 HPV genomes per PCR. When comparing the two assays, there was an excellent agreement in detecting dominant HPV types; however, we also obtained evidence for a higher sensitivity of the BSwart assay for multiple infections in these cutaneous warts. Using BSwart, HPV was found in 95% of wart preparations, with HPV1 being most prevalent, followed by types 27, 57, and 2. Both novel BSwart and HSL-PCR/MPG HPV genotyping assays are powerful high-throughput tools that could be used to learn more about the natural history of cutaneous HPV. They would be advantageous to monitor the efficacy of future skin HPV vaccines and to identify novel HPV vaccine candidates.
Schmitt, Markus; de Koning, Maurits N. C.; Eekhof, Just A. H.; Quint, Wim G. V.; Pawlita, Michael
Human papillomaviruses (HPV) of the genera alpha, mu, and nu induce benign tumors of the cutaneous epithelia that constitute a significant burden for immunocompromised adults. Currently, no gold standard for genotyping of these HPV types exists. In this study, we describe the prevalence of genus alpha, mu, and nu HPV types in cutaneous warts. We developed a novel multiplex HPV genotyping assay, BSwart-PCR/MPG (BSwart), to type sensitively and specifically 19 cutaneous HPV types frequently found in warts. BSwart-PCR/MPG is based on a multiplex PCR using broad-spectrum primers and subsequent multiplex hybridization to type-specific probes coupled to Luminex beads. In a first application comprising 100 cutaneous warts, the assay was compared to another, recently described genotyping assay, the HSL-PCR/MPG. When a 10-fold dilution series was used, the detection limit was between 10 and 100 HPV genomes per PCR. When comparing the two assays, there was an excellent agreement in detecting dominant HPV types; however, we also obtained evidence for a higher sensitivity of the BSwart assay for multiple infections in these cutaneous warts. Using BSwart, HPV was found in 95% of wart preparations, with HPV1 being most prevalent, followed by types 27, 57, and 2. Both novel BSwart and HSL-PCR/MPG HPV genotyping assays are powerful high-throughput tools that could be used to learn more about the natural history of cutaneous HPV. They would be advantageous to monitor the efficacy of future skin HPV vaccines and to identify novel HPV vaccine candidates. PMID:21813725
Schmitt, Markus; de Koning, Maurits N C; Eekhof, Just A H; Quint, Wim G V; Pawlita, Michael
Background Several studies have assessed the epidemiology of HPV infection among MSM, but no qualitative studies have specifically assessed how HPV and genital warts (GW) affect South American men who have sex with men (MSM) and male-to-female transgendered women (TG). This study explored the knowledge, attitudes and experiences of Peruvian MSM and TG regarding HPV and GW. Methods We performed a qualitative study consisting of fifteen in-depth interviews and three focus groups carried out in Lima, Peru with diverse MSM and TG groups, including sex workers. Resulting data were analyzed by applying a systematic comparative and descriptive content analysis. Results While knowledge of HPV was limited, awareness of GW was common, particularly among TG persons and sex workers. Still, few participants recognized that GW are sexually transmitted, and many had problems differentiating between GW and other STI/anogenital conditions. Stigmatizing experiences were common during sexual encounters with people who had visible GW. Shame, emotional and physical troubles, and embarrassing sexual experiences were reported by individuals with GW. Search for treatment was mediated by peers, but stigma and apparent health services’ inability to deal with GW limited the access to effective medical care. Conclusions In Peru, public health interventions should strengthen services for HPV/GW management and increase accurate knowledge of the transmission, treatment, and sequelae of HPV/GW in MSM and TG populations.
Nurena, Cesar R.; Brown, Brandon; Galea, Jerome T.; Sanchez, Hugo; Blas, Magaly M.
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.
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.
Aim: To investigate the incidence of human papilloma virus (HPV) types 16, 18 in upper genital tract of women considered at a high risk (HR) of developing epithelial ovarian cancer (EOC). Methods: HPV 16 and 18 E6 ORF specific semiquantitative PCR was used to screen the incidence of HPV in 20 women at HR of developing EOC and 10 women with no ovarian disease (control). Results: The HR subset of fallopian tubes and ovarian tissues showed greater positivity for HPV E6 ORF (40%) as compared to control (10%) tissues. Of all the samples, two (10%) were positive for HPV 16, two (10%) were positive for HPV 18, and four (20%) showed positivity for mixed HPV 16/18 infection. The presence of HPV E6 ORF was found both in the fallopian tubes and ovarian DNA from 6 (30%) patients. In two cases (10%) we detected HPV ORF only in the fallopian tube derived genomic DNA. Conclusion: It has been shown the presence of HPV in the upper genital tract in women at HR of developing EOC in close proximity of HPV susceptible tissue cervix. PMID:24980768
Bilyk, O O; Pande, N T; Pejovic, T; Buchinska, L G
Human genital tumors as well as recurrent laryngeal papillomas were analyzed for the presence of human papillomavirus (HPV) 6 and HPV 11 sequences. HPV 11 DNA was found in 7 of 14 laryngeal papillomas; in the 7 other tumors no HPV DNA was demonstrated. HPV 11 DNA was also found in all five atypical condylomata of the cervix included in
Lutz Gissmann; Lutz Wolnik; Hans Ikenberg; Ursula Koldovsky; Hans Georg Schnurch; Harald Zur Hausen
The line blot assay, a gene amplification method that combines PCR with nonisotopic detection of amplified DNA, was evaluated for its ability to detect human papillomavirus (HPV) DNA in genital specimens. Processed samples were amplified with biotin-labeled primers for HPV detection (primers MY09, MY11, and HMB01) and for ?-globin detection (primers PC03 and PC04). Amplified DNA products were hybridized by a reverse blot method with oligonucleotide probe mixtures fixed on a strip that allowed the identification of 27 HPV genotypes. The line blot assay was compared to a standard consensus PCR test in which HPV amplicons were detected with radiolabeled probes in a dot blot assay. Two hundred fifty-five cervicovaginal lavage specimens and cervical scrapings were tested in parallel by both PCR tests. The line blot assay consistently detected 25 copies of HPV type 18 per run. The overall positivity for the DNA of HPV types detectable by both methods was 37.7% (96 of 255 samples) by the line blot assay, whereas it was 43.5% (111 of 255 samples) by the standard consensus PCR assay. The sensitivity and specificity of the line blot assay reached 84.7% (94 of 111 samples) and 98.6% (142 of 144 samples), respectively. The agreement for HPV typing between the two PCR assays reached 83.9% (214 of 255 samples). Of the 37 samples with discrepant results, 33 (89%) were resolved by avoiding coamplification of ?-globin and modifying the amplification parameters. With these modifications, the line blot assay compared favorably to an assay that used radiolabeled probes. Its convenience allows the faster analysis of samples for large-scale epidemiological studies. Also, the increased probe spectrum in this single hybridization assay permits more complete type discrimination.
Coutlee, Francois; Gravitt, Patti; Richardson, Harriet; Hankins, Catherine; Franco, Eduardo; Lapointe, Normand; Voyer, Helene
A novel real-time PCR assay for detection of human papillomavirus type 52 (HPV-52) DNA (RT-52) was evaluated on 265 anogenital samples. RT-52 had a sensitivity of 98.4% and a specificity of 100% compared to conventional HPV-52 typing assays, including hybridization of PGMY products with an HPV-52-specific probe and PCR sequencing of HPV-52 E6. PMID:17898159
Coutlée, François; Rouleau, Danielle; Ghattas, Georges; Hankins, Catherine; Vézina, Sylvie; Coté, Pierre; Macleod, John; de Pokomandy, Alexandra; Money, Deborah; Walmsley, Sharon; Voyer, Hélène; Brassard, Paul; Franco, Eduardo
Background.?Diagnoses of genital warts (GW) in genitourinary medicine (GUM) clinics have been increasing in England for many years. In 2008, an HPV immunization program began with a bivalent vaccine (Cervarix). This was expected to markedly reduce infections and disease due to human papillomavirus (HPV) 16/18 but not HPV 6/11 infections or disease. However, from 2009 to 2011 there were decreases in reported diagnoses of GW in young females at GUM clinics. Methods.?Using data from GUM clinics and a sample of general practices (GPs) throughout England, we analyzed rates of GW diagnoses by age, year of diagnosis, and estimated immunization coverage. Results.?The overall reduction in GW diagnoses at GUM clinics between 2008 and 2011 was 13.3% among 16- to 19-year-old females, with the greatest decline of 20.8% in 17-year-olds. Declines were positively associated with estimated immunization coverage. A similar pattern was seen in GP diagnoses, but not among older women, and for other GUM consultations. Conclusions.?Several factors might contribute to declines in GW. However, the size and pattern of the declines strongly suggest that we are observing an unexpected, moderately protective effect of HPV 16/18 vaccination against GW.
Howell-Jones, Rebecca; Soldan, Kate; Wetten, Sally; Mesher, David; Williams, Tim; Gill, O. Noel; Hughes, Gwenda
Accurate HPV typing is important for natural history and epidemiology studies. With the introduction of prophylactic multivalent HPV vaccines, there is also the need to determine the dominant genotypes in different populations and the effect of a vaccination programme on infection profiles. The interplay between multiple infection, viral persistence and implementation of interventions is a complicated one and therefore requires a reliable and accurate HPV detection and typing method. The Linear Array HPV genotyping test is a PCR-based HPV detection kit which can detect qualitatively Multiple HPV Infection in cervical cells collected in PreservCyt Solution. The utility of this kit for multiple HPV typing of archival frozen tissue and cervical cells not collected in PreservCyt are described. PMID:17320976
Woo, Yin Ling; Damay, Isabelle; Stanley, Margaret; Crawford, Robin; Sterling, Jane
HIV-infected individuals experience more persistent HPV infections and are less likely to resolve genital warts. This study compared phenotype and functions of NK and T cells from genital warts and blood from 67 women. We compared in vitro functional responses of NK and T cells by multiparametric flow cytometry. HIV+ women had significantly lower frequencies of CD4 T cells in warts (p = 0.001) and blood (p = 0.001). While the distribution of NK cell subsets was similar, HIV+ women tended to have lower frequencies of CD56(Dim) NK cells in both blood (p = 0.0001) and warts (p = 0.006) than HIV- women. Wart NK cells from HIV+ women expressed significantly lower CD107a and produced IFN-?. HAART status was not associated with differences in NK cell functionality. We conclude that wart NK cells from HIV+ women have defects in their ability to degranulate and/or secrete IFN-?, which may provide insights into why HIV+ women fail to spontaneously resolve genital warts. PMID:24440646
Bere, Alfred; Tayib, Shahila; Kriek, Jean-Mari; Masson, Lindi; Jaumdally, Shameem Z; Barnabas, Shaun L; Carr, William H; Allan, Bruce; Williamson, Anna-Lise; Denny, Lynette; Passmore, Jo-Ann S
Quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine (gardasil(®)): a review of its use in the prevention of premalignant anogenital lesions, cervical and anal cancers, and genital warts.
Quadrivalent human papillomavirus (HPV) [types 6, 11, 16, 18] recombinant vaccine (Gardasil(®); Silgard(®)) is composed of virus-like particles formed by self-assembly of recombinant L1 capsid protein from each of HPV types 6, 11, 16 and 18. It is indicated for use from the age of 9 years as a two- or three-dose vaccination course over 6 months for the prevention of premalignant anogenital lesions, cervical and anal cancers, and genital warts caused by the vaccine HPV types. In placebo-controlled trials, quadrivalent HPV vaccine provided high-level protection against infection or disease caused by the vaccine HPV types over 2-4 years in females aged 15-45 years who were negative for the vaccine HPV types, and provided a degree of cross-protection against certain non-vaccine HPV types. The vaccine also provided high-level protection against persistent infection, anogenital precancerous lesions and genital warts caused by the vaccine HPV types over 3 years in susceptible males aged 16-26 years. Protection has been demonstrated for up to 8 years. In subjects who were negative for the vaccine HPV types, high seroconversion rates and high levels of anti-HPV antibodies were observed in females of all age ranges from 9 to 45 years and in males aged 9-26 years. The vaccine was generally well tolerated and was usually predicted to be cost effective in girls and young women. Therefore, quadrivalent HPV vaccine offers an effective means to substantially reduce the burden of HPV-related anogenital disease in females and males, particularly cervical cancer and genital warts. PMID:25022951
McCormack, Paul L
Background:In 2008, a national human papillomavirus (HPV) immunisation programme began in Scotland for 12-13 year old females with a three-year catch-up campaign for those under the age of 18. Since 2008, three-dose uptake of bivalent vaccine in the routine cohort aged 12-13 has exceeded 90% annually, while in the catch-up cohort overall uptake is 66%.Methods:To monitor the impact of HPV immunisation, a programme of national surveillance was established (pre and post introduction) which included yearly sampling and HPV genotyping of women attending for cervical screening at age 20. By linking individual vaccination, screening and HPV testing records, we aim to determine the impact of the immunisation programme on circulating type-specific HPV infection particularly for four outcomes: (i) the vaccine types HPV 16 or 18 (ii) types considered to be associated with cross-protection: HPV 31, 33 or 45; (iii) all other high-risk types and (iv) any HPV.Results:From a total of 4679 samples tested, we demonstrate that three doses (n=1100) of bivalent vaccine are associated with a significant reduction in prevalence of HPV 16 and 18 from 29.8% (95% confidence interval 28.3, 31.3%) to 13.6% (95% confidence interval 11.7, 15.8%). The data also suggest cross-protection against HPV 31, 33 and 45. HPV 51 and 56 emerged as the most prevalent (10.5% and 9.6%, respectively) non-vaccine high-risk types in those vaccinated, but at lower rates than HPV 16 (25.9%) in those unvaccinated.Conclusions:This data demonstrate the positive impact of bivalent vaccination on the prevalence of HPV 16, 18, 31, 33 and 45 in the target population and is encouraging for countries which have achieved high-vaccine uptake. PMID:24736582
Kavanagh, K; Pollock, K G J; Potts, A; Love, J; Cuschieri, K; Cubie, H; Robertson, C; Donaghy, M
Human papillomavirus (HPV) is the central etiologic factor for cervical cancer, and prior studies suggested C. trachomatis may act as an HPV cofactor. We examined the C. trachomatis—cervical cancer association by serotype, histology, HPV type in the tumor, and other HPV cofactors. We conducted a population-based study in the Seattle-Puget Sound area of 302 women with invasive squamous cell carcinomas (SCC), 185 women with adenocarcinomas of the cervix (AC), and 318 HPV seropositive control women. The risk of SCC associated with antibodies to C. trachomatis was increased (OR 1.6, 95% CI 1.1–2.2) but not for AC (OR 1.0, 95% CI 0.6–1.5). This association was independent of HPV type in the SCC tumor tissue. There was an association between specific serotypes of C. trachomatis and SCC for 6 of the 10 serotypes: B (OR 3.6, 95% CI 1.5–8.4), D (OR 2.1, 95% CI 1.2–3.5), E (OR 2.4, 95% CI 1.4–3.9), G (OR 3.0, 95% CI 1.1–7.9), I (OR 4.2, 95% CI 1.5–11.7), and J (OR 2.3, 95% CI 1.0–5.1), but not for the 4 types (C, F, H, and K) that were present at very low prevalence in this population. There was an increased risk of SCC, but not AC, associated with antibodies to C. trachomatis that was not serotype specific.
Madeleine, Margaret M.; Anttila, Tarja; Schwartz, Stephen M.; Saikku, Pekka; Leinonen, Maija; Carter, Joseph J.; Wurscher, Michelle; Johnson, Lisa G.; Galloway, Denise A.; Daling, Janet R.
The prevalence of HIV and HPV is high among men who have sex with men (MSM) in China. It is unclear whether cognitive and affective responses related to HPV and HPV-related diseases are negatively associated with HIV-related risk behaviors among MSM. This cross-sectional study interviewed 449 adult Chinese MSM in Hong Kong. The prevalence of unprotected anal intercourse (UAI) and having had anal sex with more than one man in the last 6 months (multiple male sex partnerships) was 39.0 and 71.3 %, respectively. After adjusting for four significant background variables (education level, cohabitation with a man, exposure to HIV prevention materials, and HIV voluntary counseling and testing), variables negatively associated with UAI and/or multiple male sex partnerships included (1) correct HPV-related knowledge (AOR = 0.48-0.66), (2) perceived susceptibility (AOR = 0.32-0.55) and perceived severity (AOR = 0.12-0.60) related to HPV and HPV-related diseases, and (3) fear towards contracting genital warts and penile/anal cancer (AOR = 0.40-0.55). Perceived high chance of contracting HPV was positively associated with multiple partnerships (AOR = 4.74). It is possible to reduce HIV-related risk behaviors by increasing levels of knowledge, cognitions, and fear related to HPV and related diseases. It is important to integrate prevention of HIV with prevention of sexually transmitted infections. Such interventions are warranted. PMID:23982568
Lau, Joseph T F; Wang, Zixin; Lau, Mason; Lai, Coco H Y
The aim of this study was to evaluate the total burden and health care provider costs of prevention, management and treatment of HP-related genital disease outcomes including all organized and opportunistic screening tests. Information about HPV-related disease outcomes in the Finnish female population of 2.7 million was obtained from nationwide population-based registry data. We estimated the incidence, health care resource use, health provider costs and life years lost due to cervical, vaginal and vulvar cancer and intraepithelial neoplasia (CIN, VaIN, VIN), cervical adenocarcinoma in situ, and external genital warts. The average annual disease burden of HPV-related genital disease in the female population of Finland comprises altogether 241 cases of cervical, vaginal and vulvar cancer, 2,898 new cases of CIN, 34,432 cases of minor cytological abnormalities, and almost 4,000 cases of external genital warts. The total annual costs of screening, further diagnostics and treatment of HPV-related genital disease were € 44.7 million of which the annual costs due to cervical cancer screening were € 22.4 million and due to diagnostics, management and treatment of HPV-related genital disease outcomes were € 22.3 million. The latter included € 8.4 million due to minor cervical abnormalities detected by the current cervical screening practice. The extensive opportunistic Pap testing fails to keep the incidence of cervical cancer from increasing among women aged 30-34. In addition opportunistic screening among this and younger age group detects a significant number of cytological abnormalities, most of which are probably treated unnecessarily. PMID:23463194
Salo, Heini; Leino, Tuija; Kilpi, Terhi; Auranen, Kari; Tiihonen, Petri; Lehtinen, Matti; Vänskä, Simopekka; Linna, Miika; Nieminen, Pekka
The human papillomavirus (HPV) causes more than 99% of all cervical cancers (see Am J Med Resource Center: http://supplements.amjmed.com/2011/HPV/). Exposure to HPV infections occurs in a high proportion of the overall population; however, 2 safe and effective vaccines, HPV2 and HPV4, are approved for the prevention of HPV-16 and HPV-18 infection, the most common causes of cervical cancer. Additionally, HPV4 prevents HPV-6 and HPV-11-related genital warts. While prevention of cervical cancer in women has been the initial aim of vaccination programs, it has now become apparent that HPV causes other types of cancer as well, including vulvar and vaginal cancers in women, penile cancer in men, and anal cancer in both sexes. Furthermore, these viruses have been implicated in head and neck cancers in both men and women as well. It is estimated that HPV-related cancers occur in 10,000 American males annually, suggesting that limiting vaccination programs to females may be underserving a significant proportion of the population. The efficacy of the 2 available vaccines against oncogenic HPV is more than 90% for both cervical and anal intraepithelial neoplasia. For those receiving the HPV4 vaccine, efficacy against genital warts is nearly 90%. Adverse effects are few and include episodes of syncope in the period immediately following vaccination. Benefits of vaccinating males include reduction in disease burden in men and enhanced herd immunity to reduce disease burden in women. PMID:22727241
Alexander, Kenneth A; Giuliano, Anna R
The knowledge on risk factors of being human papillomavirus (HPV)-positive among older women is sparse. The aim was to determine the frequency of oncogenic HPV appearance after 7 years among initially HPV-negative women and to examine potential risk factors that influence the occurrence of HPV in older women using multiple logistic regression. For comparison, a younger cohort of women examined under identical study settings was included. This prospective cohort study comprised 1,577 older women (age 40-50 at enrolment) and 2,920 women aged 22-32. Participants were interviewed and underwent a gynecological examination at two time points (7 years apart). Cervical samples were tested for HPV using Hybrid Capture 2 (HC2) and only women who tested HC2-negative at baseline were included. The HPV prevalence among older and younger women was 6.4% and 10.7%, respectively, and there was no "second peak" observed among older women. Recent sexual partners were a strong determinant of HPV appearance irrespective of age. Lifetime number of sexual partners was a significant risk factor for HPV appearance among older women, even after adjustment for recent sexual behavior. In addition, menopause was associated with a non-significantly increased risk of HPV appearance at follow-up. In conclusion, appearance of HPV in previously HPV-negative older women may be due to both recent sexual behavior and previous exposure that is, reactivation of a latent HPV infection. PMID:24610211
Brogaard, Kim Agerholm; Munk, Christian; Iftner, Thomas; Frederiksen, Kirsten; Kjaer, Susanne K
Genital infection with human papillomavirus (HPV) is a common STI. Reliable estimates indicate a lifetime risk of infection of more than 50% for the population. Genital HPV infection can be divided into infection with genotypes less likely to be associated with neoplasia (low oncogenic risk) and genotypes with a stronger association with neoplasia (high oncogenic risk). A family of high-risk
Charles JN Lacey
Background Primary squamous cell carcinoma (SCC) of the upper genital tract, including the endometrium, fallopian tubes, and ovaries, is extremely rare. It must be distinguished from the mucosal extension of primary cervical SCC because determination of the primary tumor site is important for tumor staging. However, patients with SCC of the fallopian tubes or ovarian surface have often undergone prior hysterectomy with inadequate examination of the cervix, making it difficult to determine the primary site. Methods We compared histologic findings, p16INK4a expression, and human papillomavirus (HPV) DNA status in four patients with primary SCC of the upper genital tract and five patients with primary cervical SCC extending to the mucosa of the upper genital tract. Results All five SCCs of cervical origin showed strong expression of p16INK4a, whereas all four SCCs of the upper genital tract were negative, although one showed weak focal staining. Three of the five cervical SCCs were positive for HPV16 DNA, whereas all four primary SCCs of the upper genital tract were negative for HPV DNA. Conclusions Although a thorough histological examination is important, immunonegativity for p16INK4a and negative for HPV DNA may be useful adjuncts in determining primary SCCs of the upper genital tract.
Yoo, Su Hyun; Son, Eun-Mi; Sung, Chang Okh
The aim of this study was to determine human papillomavirus (HPV) types distribution in cervical preneoplasic lesions in a Southern Spanish population and their relationship between HPV type and grade of histopathological abnormality. Finally, 232 cervical samples from 135 women with previous cytological abnormalities were included in this study. Colposcopy studies and biopsies were performed. Haematoxylin-eosin stained slides were observed and detection of HPV DNA in cervical swabs was carried out with use of a polymerase chain reaction and microarrays technology. The relationship between the presence of HPV infection and diagnostic variables was evaluated. HPV 16 was the most common type followed by HPV 58, 51, 33 and 31. However, the two HPV types targeted in the prophylactic vaccines such as HPV type 16 and 18 were detected in only 37 (21.2%) and 2 (1.1%) cases respectively. Thirty-three (18.9%) of samples were infected with multiple types, the majority of them with two types. In addition, during the follow-up of patients many changes in type distribution were observed. Several studies will be necessary in order to evaluate the HPV type distribution for therapeutically and prophylactic purposes such as vaccine treatment. Also, because of the differences obtained depending of use of various DNA technologies, the performance of some comparative studies of the different methods from detection of HPV would be advisable in a high population of patients and with the most homogeneous conditions possible.
Cobo, Fernando; Concha, Angel; Ortiz, Marta
The identification of the types of the human papil- lomavirus (HPV) that have infected a female patient provides valuable information as regards to her risk for developing cervical cancer. A widely used method for performing the above task (namely HPV typing) is PCR-RFLP gel electrophoresis. However, the conventional HPV typing protocol is error-prone and resource-ineffective due to lack of interaction
Christos F. Maramis; Anastasios N. Delopoulos; Alexandros F. Lambropoulos; Sokratis P. Katafigiotis
Human papillomavirus (HPV) infection is the leading cause of cervical cancer world-wide. Here, we show that native HPV particles produced in a differentiated epithelium have developed different strategies to infect the host. Using biochemical inhibition assays and glycosaminoglycan (GAG)-negative cells, we show that of the four most common cancer-causing HPV types, HPV18, HPV31, and HPV45 are largely dependent on GAGs to initiate infection. In contrast, HPV16 can bind and enter through a GAG-independent mechanism. Infections of primary human keratinocytes, natural host cells for HPV infections, support our conclusions. Further, this renders the different virus types differentially susceptible to carrageenan, a microbicide targeting virus entry. Our data demonstrates that ordered maturation of papillomavirus particles in a differentiating epithelium may alter the virus entry mechanism. This study should facilitate a better understanding of the attachment and infection by the main oncogenic HPV types, and development of inhibitors of HPV infection. PMID:23861898
Cruz, Linda; Meyers, Craig
Human papillomavirus (HPV) infection is the leading cause of cervical cancer world-wide. Here, we show that native HPV particles produced in a differentiated epithelium have developed different strategies to infect the host. Using biochemical inhibition assays and glycosaminoglycan (GAG)-negative cells, we show that of the four most common cancer-causing HPV types, HPV18, HPV31, and HPV45 are largely dependent on GAGs to initiate infection. In contrast, HPV16 can bind and enter through a GAG-independent mechanism. Infections of primary human keratinocytes, natural host cells for HPV infections, support our conclusions. Further, this renders the different virus types differentially susceptible to carrageenan, a microbicide targeting virus entry. Our data demonstrates that ordered maturation of papillomavirus particles in a differentiating epithelium may alter the virus entry mechanism. This study should facilitate a better understanding of the attachment and infection by the main oncogenic HPV types, and development of inhibitors of HPV infection.
Cruz, Linda; Meyers, Craig
We explored the cutaneotropic HPV genetic diversity in 71 subjects from Argentina. New generic primers (CUT) targeting 88 mucosal/cutaneous HPV were designed and compared to FAP primers. Overall, 69 different HPV types/putative types were identified, being 17 of them novel putative types. Phylogenetic analysis of partial L1 sequences grouped 2 novel putative types in the Beta-PV, 14 in the Gamma-PV and 1 in the Mu-PV genera. CUT primers showed broader capacity than FAP primers in detecting different genera/species and novel putative types (p<0.01). Using overlapping PCR, the full-length genome of a Beta-PV putative type was amplified and cloned. The new virus, designated HPV 115, encodes 5 early genes and 2 late genes. Phylogenetic analysis indicated HPV 115 as the most divergent type within the genus Beta-PV species 3. This report is the first providing data on cutaneous HPVs circulating in South America and expands our knowledge of the Papillomaviridae family.
Chouhy, Diego; Gorosito, Mario; Sanchez, Adriana; Serra, Esteban C; Bergero, Adriana; Bussy, Ramon Fernandez; Giri, Adriana A
The identification of the types of the human papilomavirus (HPV) that have infected a woman provides valuable information as regards to her risk for developing cervical cancer. HPV typing is often performed by means of manually analyzing PCR-RFLP gel electrophoresis images. However, the typing procedure that is currently employed suffers from unsatisfactory accuracy and high time consumption. In order to
Christos F. Maramis; Anastasios N. Delopoulos; Alexandros F. Lambropoulos
Background Cervical cancer is caused by high-risk types of human papillomavirus (HPV). DNA testing of such high-risk types of HPV could improve cervical screening.The aim of the study was to compare the sensitivities and positive predictive values of two commercially available typing assays (Qiagen LQ and Roche LA) and to comparatively assess the distribution of HPV types with these two assays. Methods The study population comprised 311 ASCUS + women with abnormal pap tests who were HCII positive and who were admitted to three European referral gynecology clinics between 2007 and 2010 (Madrid, Marseille and Milan). All patients underwent LQ and LA tests. Results The sensitivity of the two assays for HPV typing was 94% for LQ and 99% for LA (compared with HCII). The overall concordance between LQ and LA was 93%. The three prevalent genotypes, HPV16, HPV18, and HPV31, were identified with a high concordance using the two assays: kappa 0.93, 0.83, and 0.91, respectively. Mixed genotypes were more frequently detected by LA than by LQ: 52% vs. 18%, respectively (p < .0001). Conclusions These assays have a good clinical sensitivity for detecting HPV types in CIN2+ patients and allow the virus type to be detected in the same experiment. Our study revealed no significant difference between LQ and LA for CIN2+ or CIN3+ diagnosis, indicating similar distributions of HPV types and a mixed genotype detection that is higher for LA than for LQ.
The aetiology of anal squamous cell carcinoma (SCC) has recently been associated with a sexually transmissible agent — human papillomavirus (HPV) type 16. In this study clinical and pathological data from a prospective series of 67 anal SCC collected over a three year period were compared with the HPV type 16 DNA content of these tumours to determine whether any
J. H. Scholefield; J. G. Palmer; N. A. Shepherd; S. Love; K. J. Miller; J. M. A. Northover
Cervical cancer results from infection with high-risk type human papillomaviruses (HPV). Therapeutic vaccines aiming at controlling existing genital HPV infections and associated lesions are usually tested in mice with HPV-expressing tumor cells subcutaneously implanted into their flank. However, effective vaccine-induced regression of these ectopic tumors strongly contrasts with the poor clinical results of these vaccines produced in patients with HPV-associated genital neoplasia. To assess HPV therapeutic vaccines in a more relevant setting, we have, here, established an orthotopic mouse model where tumors in the genital mucosa (GM) develop after an intravaginal instillation of HPV16 E6/E7-expressing tumor cells transduced with a luciferase-encoding lentiviral vector for in vivo imaging of tumor growth. Tumor take was 80-90% after nonoxynol-9 induced damage of the epithelium. Tumors remained localized in the genital tract, and histological analysis showed that most tumors grew within the squamous epithelium of the vaginal wall. Those tumors induced (i) E7-specific CD8 T cells restricted to the GM and draining lymph nodes, in agreement with their mucosal location and (ii) high Foxp3+ CD4+ infiltrates, similarly to those found in natural non-regressing HPV lesions. This novel genital HPV-tumor model by requiring GM homing of vaccine-induced immune responses able to overcome local immuno-suppression may be more representative of the situation occurring in patients upon therapeutic vaccination. PMID:20635385
Decrausaz, Loane; Gonçalves, Ana-Rita; Domingos-Pereira, Sonia; Pythoud, Christelle; Stehle, Jean-Christophe; Schiller, John; Jichlinski, Patrice; Nardelli-Haefliger, Denise
Genital human papillomaviruses (HPV) represent the most common sexually transmitted agents and are classified into low or high risk by their propensity to cause genital warts or cervical cancer, respectively. Topical microbicides against HPV may be a useful adjunct to the newly licensed HPV vaccine. A main objective in the development of novel microbicides is to block HPV entry into epithelial cells through cell surface heparan sulfate proteoglycans. In this study, selective chemical modification of the Escherichia coli K5 capsular polysaccharide was integrated with innovative biochemical and biological assays to prepare a collection of sulfated K5 derivatives with a backbone structure resembling the heparin/heparan biosynthetic precursor and to test them for their anti-HPV activity. Surface plasmon resonance assays revealed that O-sulfated K5 with a high degree of sulfation [K5-OS(H)] and N,O-sulfated K5 with a high [K5-N,OS(H)] or low [K5-N,OS(L)] sulfation degree, but not unmodified K5, N-sulfated K5, and O-sulfated K5 with low levels of sulfation, prevented the interaction between HPV-16 pseudovirions and immobilized heparin. In cell-based assays, K5-OS(H), K5-N,OS(H), and K5-N,OS(L) inhibited HPV-16, HPV-18, and HPV-6 pseudovirion infection. Their 50% inhibitory concentration was between 0.1 and 0.9 mug/ml, without evidence of cytotoxicity. These findings provide insights into the design of novel, safe, and broad-spectrum microbicides against genital HPV infections. PMID:18250186
Lembo, David; Donalisio, Manuela; Rusnati, Marco; Bugatti, Antonella; Cornaglia, Maura; Cappello, Paola; Giovarelli, Mirella; Oreste, Pasqua; Landolfo, Santo
Genital human papillomaviruses (HPV) represent the most common sexually transmitted agents and are classified into low or high risk by their propensity to cause genital warts or cervical cancer, respectively. Topical microbicides against HPV may be a useful adjunct to the newly licensed HPV vaccine. A main objective in the development of novel microbicides is to block HPV entry into epithelial cells through cell surface heparan sulfate proteoglycans. In this study, selective chemical modification of the Escherichia coli K5 capsular polysaccharide was integrated with innovative biochemical and biological assays to prepare a collection of sulfated K5 derivatives with a backbone structure resembling the heparin/heparan biosynthetic precursor and to test them for their anti-HPV activity. Surface plasmon resonance assays revealed that O-sulfated K5 with a high degree of sulfation [K5-OS(H)] and N,O-sulfated K5 with a high [K5-N,OS(H)] or low [K5-N,OS(L)] sulfation degree, but not unmodified K5, N-sulfated K5, and O-sulfated K5 with low levels of sulfation, prevented the interaction between HPV-16 pseudovirions and immobilized heparin. In cell-based assays, K5-OS(H), K5-N,OS(H), and K5-N,OS(L) inhibited HPV-16, HPV-18, and HPV-6 pseudovirion infection. Their 50% inhibitory concentration was between 0.1 and 0.9 ?g/ml, without evidence of cytotoxicity. These findings provide insights into the design of novel, safe, and broad-spectrum microbicides against genital HPV infections.
Lembo, David; Donalisio, Manuela; Rusnati, Marco; Bugatti, Antonella; Cornaglia, Maura; Cappello, Paola; Giovarelli, Mirella; Oreste, Pasqua; Landolfo, Santo
The exploratory immunogenicity objective of this analysis was to characterize the titer of vaccine human papillomavirus (HPV)-type immunoglobulins in both peripartum maternal blood and the cord blood of infants born to women who received blinded therapy. Data were derived from a randomized, placebo-controlled, double-blind safety, immunogenicity, and efficacy study (protocol 019; NCT00090220). This study enrolled 3,819 women between the ages of 24 and 45 years from 38 international study sites between 18 June 2004 and 30 April 2005. Data in the current analysis are from subjects enrolled in Philippines and Thailand. For each of HPV types 6, 11, 16, and 18, maternal anti-HPV was found in cord blood samples. Furthermore, HPV titers in cord blood samples were highly positively correlated with maternal HPV titers. Additionally, there were instances when anti-HPV antibodies were no longer detectable in maternal serum samples and yet were detected in matched cord blood samples. These results demonstrate that quadrivalent HPV (qHPV) vaccine-induced antibodies cross the placenta and could potentially provide some benefit against vaccine-type HPV infection and related diseases such as recurrent respiratory papillomatosis. PMID:22518014
Matys, Katie; Mallary, Sara; Bautista, Oliver; Vuocolo, Scott; Manalastas, Ricardo; Pitisuttithum, Punee; Saah, Alfred
The novel PGMY L1 consensus primer pair is more sensitive than the MY09 and MY11 primer mix for detection and typing with PCR of human papillomavirus (HPV) DNA in genital specimens. We assessed the diagnostic yield of PGMY primers for the detection and typing of HPV by comparing the results obtained with PGMY09\\/PGMY11 and MY09\\/MY11\\/HMB01 on 299 genital samples. Amplicons
François Coutlée; Patti Gravitt; Janet Kornegay; Catherine Hankins; Harriet Richardson; Normand Lapointe; Hélène Voyer; Eduardo Franco
The Roche PGMY primer-based research prototype line blot assay (PGMY-LB) is a convenient tool in epidemiological studies for the detection and typing of human papillomavirus (HPV) DNA. This assay has been optimized and is being commercialized as the Linear Array HPV genotyping test (LA-HPV). We assessed the agreement between LA-HPV and PGMY-LB for detection and typing of 37 HPV genotypes in 528 anogenital samples (236 anal, 146 physician-collected cervical, and 146 self-collected cervicovaginal swabs) obtained from human immunodeficiency virus-seropositive individuals (236 men and 146 women). HPV DNA was detected in 433 (82.0%) and 458 (86.7%) samples with PGMY-LB and LA-HPV (P = 0.047), respectively, for an excellent agreement of 93.8% (kappa = 0.76). Of the 17,094 HPV typing results, 16,562 (1,743 positive and 14,819 negative results) were concordant between tests (agreement = 96.9%; kappa = 0.76). The mean agreement between tests for each type was 96.4% +/- 2.4% (95% confidence interval [CI], 95.6% to 97.2%; range, 86% to 100%), for an excellent mean kappa value of 0.85 +/- 0.10 (95% CI, 0.82 to 0.87). However, detection rates for most HPV types were greater with LA-HPV. The mean number of types per sample detected by LA-HPV (4.2 +/- 3.4; 95% CI, 3.9 to 4.5; median, 3.0) was greater than that for PGMY-LB (3.4 +/- 3.0; 95% CI, 3.1 to 3.6; median, 2.0) (P < 0.001). The number of types detected in excess by LA-HPV in anal samples correlated with the number of types per sample (r = 0.49 +/- 0.06; P = 0.001) but not with patient age (r = 0.03 +/- 0.06; P = 0.57), CD4 cell counts (r = 0.06 +/- 0.06; P = 0.13), or the grade of anal disease (r = -0.11 +/- 0.06; P = 0.07). LA-HPV compared favorably with PGMY-LB but yielded higher detection rates for newer and well-known HPV types. PMID:16757590
Coutlée, François; Rouleau, Danielle; Petignat, Patrick; Ghattas, Georges; Kornegay, Janet R; Schlag, Peter; Boyle, Sean; Hankins, Catherine; Vézina, Sylvie; Coté, Pierre; Macleod, John; Voyer, Hélène; Forest, Pierre; Walmsley, Sharon; Franco, Eduardo
... taken in its entirety from the CDC HPV (Human Papillomavirus) Cervarix® Vaccine Information Statement: http://www.cdc. ... What is HPV? Genital human papillomavirus (HPV) is the most common ... in the United States. More than half of sexually active men ...
Human papillomavirus (HPV) infection is the most common sexually transmitted infection in both men and women, but there are limited data comparing the prevalence of HPV infection between genders and in different anogenital sites. This cross-sectional analysis describes the distribution of HPV types in the genital tract of 3,410 consecutive females and 1,033 males undergoing voluntary screening for HPV and referred to a single institution. The relationship between specific HPV types and the presence of anogenital lesions was examined. In both females and males, the overall prevalence of HPV infection was about 40%. A wide variety of HPV types was identified, but the prevalence of different types was remarkably similar in the two genders, even when considering different anatomical sites. HPV-6 was the most frequent (prevalence 13%) type in all anogenital sites in men followed by HPV-16 (7%), while HPV-16 was the most common type in women (about 6%), either in the cervix, vagina, or vulva, followed by HPV-6. In addition to HPV-16, HPV-58, HPV-33, HPV-31, and HPV-56 were the carcinogenic types detected most commonly and were significantly associated with high-grade squamous intraepithelial cervical lesions, while HPV-53 and HPV-66 were the most common among possibly carcinogenic types. In both genders, anogenital warts were associated with HPV-6 and HPV-11 infection, and, less frequently, with other types, like HPV-54, HPV-62, and HPV-66. These results show that genital HPV infection involves numerous HPV types, which have similar distribution patterns in females and males and in different anogenital anatomical sites. PMID:20572068
Barzon, Luisa; Militello, Valentina; Pagni, Silvana; Franchin, Elisa; Dal Bello, Federico; Mengoli, Carlo; Palù, Giorgio
Human papilloma virus (HPV) is the most common sexually transmitted disease in the world. Almost 80% of the world's population is exposed by the age of 50. HPV can cause oropharyngeal, genital, and anal cancers. It also causes genital warts. There is no cure for HPV but vaccines are available to prevent infection by the most common HPV viruses; unfortunately, usage is low. Most people will clear HPV spontaneously. Those who do not are at high risk for developing malignancy. Treatment mainstays are destruction and excision of the lesions. PMID:22828099
Hathaway, Jon K
Peptide dendrimers consist of a peptidyl branching core and/or covalently attached surface functional units. They show a variety of biological properties, including antiviral activity. In this study, a minilibrary of linear, dimeric, and dendrimeric peptides containing clusters of basic amino acids was evaluated for in vitro activity against human papillomaviruses (HPVs). The peptide dendrimer SB105-A10 was found to be a potent inhibitor of genital HPV types (i.e., types 16, 18, and 6) in pseudovirus-based neutralization assays. The 50% inhibitory concentration was between 2.8 and 4.2 ?g/ml (0.59 and 0.88 ?M), and no evidence of cytotoxicity was observed. SB105-A10 interacts with immobilized heparin and with heparan sulfates exposed on the cell surface, most likely preventing virus attachment. The findings from this study indicate SB105-A10 to be a leading candidate compound for further development as an active ingredient of a topical microbicide against HPV and other sexually transmitted viral infections.
Donalisio, Manuela; Rusnati, Marco; Civra, Andrea; Bugatti, Antonella; Allemand, Donatella; Pirri, Giovanna; Giuliani, Andrea; Landolfo, Santo; Lembo, David
Peptide dendrimers consist of a peptidyl branching core and/or covalently attached surface functional units. They show a variety of biological properties, including antiviral activity. In this study, a minilibrary of linear, dimeric, and dendrimeric peptides containing clusters of basic amino acids was evaluated for in vitro activity against human papillomaviruses (HPVs). The peptide dendrimer SB105-A10 was found to be a potent inhibitor of genital HPV types (i.e., types 16, 18, and 6) in pseudovirus-based neutralization assays. The 50% inhibitory concentration was between 2.8 and 4.2 ?g/ml (0.59 and 0.88 ?M), and no evidence of cytotoxicity was observed. SB105-A10 interacts with immobilized heparin and with heparan sulfates exposed on the cell surface, most likely preventing virus attachment. The findings from this study indicate SB105-A10 to be a leading candidate compound for further development as an active ingredient of a topical microbicide against HPV and other sexually transmitted viral infections. PMID:20643894
Donalisio, Manuela; Rusnati, Marco; Civra, Andrea; Bugatti, Antonella; Allemand, Donatella; Pirri, Giovanna; Giuliani, Andrea; Landolfo, Santo; Lembo, David
Objective: The objective of this study was to determine whether human papillomavirus (HPV) infections are involved in the development of papillomatosis lesions of the lower female genital tract. Methods: A total of 616 biopsy specimens of genital papillomatous lesions (307 nodular and 309 papular types) from 598 patients were anaylyzed for the presence of HPV DNA sequences by polymerase chain reaction (PCR). These specimens were also examined by histopathological assessment for characteristic HPV-associated cytological changes, by immunohistochemical staining for HPV-associated antigen, and by electron microscopy for the presence of virions. Results: HPV DNA sequences were found in 97.9% (140 of 143 cases) and 1.1% (1 of 91 cases) of the nodular and papular papillomatosis cases tested, respectively. In 18 patients who had both types of papillomatosis lesions, HPV DNA was invariably found only in nodular tissues. HPV-associated antigen, koilocytosis, and virions were found in 53.6% (98 of 183 cases), 70.5% (129 of 183 cases), and 5.9% (5 of 85 cases) of nodular papillomatosis lesions tested, respectively. Conclusions: These data suggest that nodular papillomatosis was closely associated with HPV infection, but that papular papillomatosis of the lower female genital tract may have an etiology other than HPV infection,
Hu, Yao-Xiong; Ling, Han-Liang; Ye, Zhen-Zhong; Liang, Tian; Zhang, Mei-Gui; Liu, Yun-Ke; Kang, Biao; Luo, Yuan-Ji; He, Shu-Ying; Lian, Yong-Jian
BACKGROUND: Two clinically relevant high-risk HPV (HR-HPV) types 16 and 18 are etiologically associated with the development of cervical carcinoma and are also reported to be present in many other carcinomas in extra-genital organ sites. Presence of HPV has been reported in breast carcinoma which is the second most common cancer in India and is showing a fast rising trend
Suresh Hedau; Umesh Kumar; Showket Hussain; Shirish Shukla; Shailja Pande; Neeraj Jain; Abhishek Tyagi; Trivikram Deshpande; Dilafroze Bhat; Mohammad Muzaffar Mir; Sekhar Chakraborty; Y Mohan Singh; Rakesh Kumar; Kumaravel Somasundaram; Alok C Bharti; Bhudev C Das
BackgroundIncreased duration of hormonal contraceptive (HC) use may be positively associated with the risk of invasive cervical cancer.MethodsThis is a secondary analysis from the HPV Sentinel Surveillance Study. The authors examined the association between type-specific human papillomavirus (HPV) detection and current HC use among 7718 women attending 26 sexually transmitted disease, family planning and primary care clinics in the USA.ResultsThere
Khalil G Ghanem; S Deblina Datta; Elizabeth R Unger; Michael Hagensee; Judith C Shlay; Peter Kerndt; Katherine Hsu; Laura A Koutsky
Upstream Regulatory Region Alterations Found in Human Papillomavirus Type 16 (HPV-16) Isolates from Cervical Carcinomas Increase Transcription, ori Function, and HPV Immortalization Capacity in Culture?
Human papillomavirus (HPV) DNAs isolated from cervical and head and neck carcinomas frequently contain nucleotide sequence alterations in the viral upstream regulatory region (URR). Our study has addressed the role such sequence changes may play in the efficiency of establishing HPV persistence and altered keratinocyte growth. Genomic mapping of integrated HPV type 16 (HPV-16) genomes from 32 cervical cancers revealed that the viral E6 and E7 oncogenes, as well as the L1 region/URR, were intact in all of them. The URR sequences from integrated and unintegrated viral DNA were found to harbor distinct sets of nucleotide substitutions. A subset of the altered URRs increased the potential of HPV-16 to establish persistent, cell growth-altering viral-genome replication in the cell. This aggressive phenotype in culture was not solely due to increased viral early gene transcription, but also to augmented initial amplification of the viral genome. As revealed in a novel ori-dependent HPV-16 plasmid amplification assay, the altered motifs that led to increased viral transcription from the intact genome also greatly augmented HPV-16 ori function. The nucleotide sequence changes correlate with those previously described in the distinct geographical North American type 1 and Asian-American variants that are associated with more aggressive disease in epidemiologic studies and encompass, but are not limited to, alterations in previously characterized sites for the negative regulatory protein YY1. Our results thus provide evidence that nucleotide alterations in HPV regulatory sequences could serve as potential prognostic markers of HPV-associated carcinogenesis.
Lace, Michael J.; Isacson, Christina; Anson, James R.; Lorincz, Attila T.; Wilczynski, Sharon P.; Haugen, Thomas H.; Turek, Lubomir P.
Background HPV type distribution by cytological status represents useful information to predict the impact of mass vaccination on screening programs. Methods women aged from 25 to 64 who attended cervical cancer screening in five different Italian regions were tested for HPV infection with Hybrid Capture II (HCII) low and high risk probes. Women repeating Pap-test upon unsatisfactory or positive results, or as a post-treatment and post-colposcopy follow-up analysis, were excluded from our study. High risk (HR) HPV positive samples were typed using GP5+/GP6+ primed PCR, followed by Reverse Line Blot for 18 high/intermediate risk HPV types, while low risk (LR) HPV positive samples were tested with type specific primers for HPV6 and HPV11. Results 3410 women had a valid HCII and Pap-test. The prevalence of HR and LR infections was 7.0% and 3.6%, 29.1% and 13.7%, 68.1% and 31.9%, 60.0% and 0.0%, 65.0% and 12.0%, for negative, ASC-US, L-SIL, ASC-H and H-SIL cytology, respectively. The fraction of ASC-US+ cytology due to HPV 16 and 18 ranged from 11.2 (HPV 16/18 alone) to 15.4% (including HPV 16/18 in co-infection with other virus strains), and that due to HPV 6 and 11 ranged from 0.2% (HPV 6/11 alone) to 0.7% (including HPV 6/11 in co-infection with other LR virus strains). Conclusions mass vaccination with bivalent or quadrivalent HPV vaccine would modestly impact on prevalence of abnormal Pap-test in screening.
Background Cervical cancer ranks third in prevalence and fourth as cause of death in women worldwide. In Brazil, 17,540 women were diagnosed in 2012 with the disease. Persistent infection with high-risk HPV types is a necessary condition for the development of pre-invasive and invasive cervical neoplasia. Currently, over 100 HPV types have been identified, but HPV16 and 18 are recognized as the mayor culprits in cervical carcinogenesis. Our objective was to assess the relationships between single- (ST) and multiple-type (MT) HPV infections with patients’ age and lesion pathological status. Methods 328 patients with either squamous or glandular intraepithelial or invasive cervical lesion were selected. All subjects were tested for HPV genotypes with reverse hybridization for 21 high- (hr-HPV) and 16 low-risk (lr-HPV) probes. Prevalence of ST and MT HPV infections was compared across histological types and age strata. Results 287 (87%) women had at least one HPV type detected and 149 (52%) had MT infections. The most prevalent HPV type was HPV16, present in 142 cases (49% of all HPV-positive cases), followed by HPV58, 52, 31, 35 and 33. HPV18, in single or multiple infections, occurred in 23 cases (8% of hr-HPV cases). Almost all glandular lesions were associated with HPV16 and 18 alone. Multiple infections were significantly more prevalent in squamous than in glandular lesion for HPV16 and 18 (P = 0.04 and 0.03 respectively). The prevalence of MT infections followed a bimodal distribution; peaking in women younger 29 years and in those aged 50 to 59. Conclusions Our data indicate that prevention strategies for pre-invasive and invasive squamous lesions should be focused on HPV16 and a few alpha-9 HPV types. It is clear to us that in young women, prophylaxis must cover a large amalgam of HPV types beyond classic HPV16 and 18.
An accurate biomarker for the follow-up of women positive for human papillomavirus type 16 (HPV16) DNA may improve the efficiency of cervical cancer prevention. Previously, we analyzed all 113 HPV16 CpGs in cervical cytology samples and discovered differential methylation at different stages of premalignancy. In the current study, we identified a methylation biomarker consisting of a panel of 12 HPV16 CpG sites in the E5, L2, and L1 open reading frames, and tested whether it fulfilled three necessary conditions of a prospective biomarker. A total of 33 cytology samples from North American and West African women with all grades of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) were analyzed by using DNA bisulfite sequencing. The results showed (i) a highly significant trend for increasing HPV16 biomarker methylation with increasing histologic severity (P < 0.0001), (ii) 100% sensitivity for ICC over a wide range of methylation cutoff scores; 80% detection of CIN3 at cutoff scores up to 39% methylation, and (iii) substantially lower detection of CIN2, from 0% to 71%, depending on the cutoff score. Our results support the prognostic potential of the HPV16 methylation biomarker for the triage to colposcopy of women with HPV16-positive screening tests and, eventually, for the management of women with HPV16-positive CIN2. Cancer Prev Res; 7(5); 526-33. ©2014 AACR. PMID:24556390
Brandsma, Janet L; Harigopal, Malini; Kiviat, Nancy B; Sun, Ying; Deng, Yanhong; Zelterman, Daniel; Lizardi, Paul M; Shabanova, Veronika S; Levi, Angelique; Yaping, Tian; Hu, Xinyuan; Feng, Qinghua
A double-blind, multicenter, randomized clinical trial was con- ducted to determine whether a human papillomavirus type 16 (HPV-16) vaccine could prevent HPV-16 infection in women. Female subjects (N = 2392) age 16 to 23 years were randomly assigned to receive 3 injections of either HPV-16 vaccine or placebo at day 0, month 2, and month 6. Genital samples to test
Jennifer M. Lehr
Among sexually transmitted diseases, infection by human papillomavirus (HPV) has become one of the most important. On the other hand, though epidemiological data show that some HPV types are closely associated with cervical cancer, few reports have been found with reference to penile carcinoma because of its rare occurrence. The aim of this study was to investigate the relationship between HPV infection and penile cancer in Argentina. A retrospective study was carried out on 38 white men with penile squamous-cell carcinoma. Sixty-five archival fixed biopsies taken from 34 primary penile tumors, 25 nodal metastases, 1 skin "satellite" metastasis and 5 histologically normal lymph nodes were used as specimens. HPV detection and typing were carried out by the polymerase chain reaction (PCR) using generic primers, combined with single-stranded conformational polymorphism (SSCP) analysis. HPV DNA was found in 71% patients, corresponding 81% of them to "high risk" types, with predominance of HPV 18. Both primary tumors and metastases showed concordance of HPV occurrence and type in both lesions. In 3 patients, HPV 16 was detected not only in primary tumors and metastases, but also in histologically normal lymph nodes. Our data indicate that most penile carcinomas in Argentine patients are etiologically related to HPV, especially to "high risk" genital types. The agreement in HPV detection between primary tumors and metastases suggests a potential viral role in tumor progression. HPV detection in otherwise histologically normal lymph nodes might be useful as early marker of a metastatic process. PMID:10745234
Picconi, M A; Eiján, A M; Distéfano, A L; Pueyo, S; Alonio, L V; Gorostidi, S; Teyssié, A R; Casabé, A
Background Current human papillomavirus (HPV) vaccines that are based on virus-like particles (VLPs) of the major capsid protein L1 largely elicit HPV type-specific antibody responses. In contrast, immunization with the HPV minor capsid protein L2 elicits antibodies that are broadly cross-neutralizing, suggesting that a vaccine targeting L2 could provide more comprehensive protection against infection by diverse HPV types. However, L2-based immunogens typically elicit much lower neutralizing antibody titers than L1 VLPs. We previously showed that a conserved broadly neutralizing epitope near the N-terminus of L2 is highly immunogenic when displayed on the surface of VLPs derived from the bacteriophage PP7. Here, we report the development of a panel of PP7 VLP-based vaccines targeting L2 that protect mice from infection with carcinogenic and non-carcinogenic HPV types that infect the genital tract and skin. Methodology/Principal Findings L2 peptides from eight different HPV types were displayed on the surface of PP7 bacteriophage VLPs. These recombinant L2 VLPs, both individually and in combination, elicited high-titer anti-L2 IgG serum antibodies. Immunized mice were protected from high dose infection with HPV pseudovirus (PsV) encapsidating a luciferase reporter. Mice immunized with 16L2 PP7 VLPs or 18L2 PP7 VLPs were nearly completely protected from both PsV16 and PsV18 challenge. Mice immunized with the mixture of eight L2 VLPs were strongly protected from genital challenge with PsVs representing eight diverse HPV types and cutaneous challenge with HPV5 PsV. Conclusion/Significance VLP-display of a cross-neutralizing HPV L2 epitope is an effective approach for inducing high-titer protective neutralizing antibodies and is capable of offering protection from a spectrum of HPVs associated with cervical cancer as well as genital and cutaneous warts.
Tumban, Ebenezer; Peabody, Julianne; Peabody, David S.; Chackerian, Bryce
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.
Aguilar, L V; Lazcano-Ponce, E; Vaccarella, S; Cruz, A; Hernandez, P; Smith, J S; Munoz, N; Kornegay, J R; Hernandez-Avila, M; Franceschi, S
Recent data demonstrate that human papilloma virus (HPV) plays a role in pathologies other than ano-genital cancers, specifically head and neck malignancies, and non-cancerous conditions such as recurrent respiratory papillomatosis (RRP). High-risk HPV16 and 18, and low risk HPV6 and 11 play the main role in HPV-related pathologies. As more and more information about the role of HPV infection in non-cervical diseases is amassed, additional questions about whether prophylactic HPV vaccines will effectively prevent these conditions are raised. HPV vaccination programs for the cervical pathology are being implemented worldwide. In the United States, the US Food and Drug Administration (FDA) approved the quadrivalent HPV vaccine for girls in 2006 and for boys in 2011. These vaccination programs were aimed at the genital, HPV-related lesions, and there was not much recognition at that time of how HPV vaccination programs might affect oral HPV infection, which is a risk factor for the development of HPV-related head and neck cancers. Vaccination has proved to be a successful policy, and an extant recommendation is aimed at preventing HPV and associated cervical and other anogenital cancers with the routine use of HPV vaccines for males and females. However, HPV vaccines are presently not recommended for preventing oropharyngeal cancer (OPC), although they have been shown to be highly effective against the HPV strains that are most commonly found in the oropharynx. This review is aimed at presenting the evidence-based knowledge concerning HPV vaccination and highlighting the trials and strategies for vaccine administration in HPV-dependent head and neck pathologies. PMID:24981297
Wierzbicka, Ma?gorzata; Józefiak, Agata; Jackowska, Joanna; Szyd?owski, Jaros?aw; Go?dzicka-Józefiak, Anna
Genital Chlamydia trachomatis (CT) infections have been identified as a major health problem concern. CT is associated with adverse effect on women reproduction and also associated with cervical hypertrophy and induction of squamous metaplasia, providing a possible relationship with human papillomavirus (HPV) infection. Infection by high-risk HPV types is crucial to the pathogenesis of invasive cervical cancer (ICC), but other co-variants/cofactors must be present for the development of malignancy. CT biological effect may damage the mucosal barrier, improving HPV infection, or may interfere in immune response and viral clearance supporting the persistence of HPV infection. Moreover, CT-related chronic cervical inflammation, decrease of lower genital tract antigen-presenting cells, inhibition of cell-mediated immunity, and anti-apoptotic capacity may influence the natural history of HPV infection, namely persistence progression or resolution. Although several epidemiological studies have stated a positive association involving CT and HPV-related cervical neoplastic lesions and/or cervical cancer (CC), the specific role of this bacterium in the pathogenesis of cervical neoplasia has not been completely clarified. The present review summarizes several studies on CT role in cervical cancer and suggests future research directions on HPV and CT interaction. PMID:24346121
Silva, Jani; Cerqueira, Fátima; Medeiros, Rui
We developed a direct sequence-based genotyping method to detect single and multiple HPV L1 DNA and RNA types in genital and dermatological specimens. Our method couples PCR amplification of a highly conserved HPV L1 segment using a broad spectrum-generic primer cocktail mix with automated sequencing of amplified PCR products, followed by GenBank sorting of sequencing data. We genotyped 5 skin and 30 cervical HPV DNA-positive specimens using this method and established its first experimentally derived working cutoff value with the aid of commercial hybridization-based techniques. We suggest that sequence-based genotyping of appropriately amplified DNA and RNA products may serve as a primary HPV detection method in dermatological specimens. It can be applied as an all-purpose genotyping method for rare HPV types not detectable by commercial hybridization-based techniques and for sorting multiple HPV infections by order of prevalence. PMID:19762162
Satra, Maria; Vamvakopoulou, Dimitra N; Sioutopoulou, Despina O; Kollia, Panagoula; Kiritsaka, Aspasia; Sotiriou, Sotirios; Antonakopoulos, Georgios; Alexandris, Elias; Costantoulakis, Pantelis; Vamvakopoulos, Nicholas C
Genotyping may improve risk stratification of high-risk (HR) human papillomavirus (HPV)-positive women in cervical screening programs; however, prospective data comparing the natural history and carcinogenic potential of individual HR types remain limited. A meta-analysis of cross-sectional HR HPV-type distribution in 115,789 HPV-positive women was performed, including 33,154 normal cytology, 6,810 atypical squamous cells of undetermined significance (ASCUS), 13,480 low-grade squamous intraepithelial lesions (LSIL) and 6,616 high-grade SIL (HSIL) diagnosed cytologically, 8,106 cervical intraepithelial neoplasia grade 1 (CIN1), 4,068 CIN2 and 10,753 CIN3 diagnosed histologically and 36,374 invasive cervical cancers (ICCs) from 423 PCR-based studies worldwide. No strong differences in HPV-type distribution were apparent between normal cytology, ASCUS, LSIL or CIN1. However, HPV16 positivity increased steeply from normal/ASCUS/LSIL/CIN1 (20-28%), through CIN2/HSIL (40/47%) to CIN3/ICC (58/63%). HPV16, 18 and 45 accounted for a greater or equal proportion of HPV infections in ICC compared to normal cytology (ICC:normal ratios = 3.07, 1.87 and 1.10, respectively) and to CIN3 (ICC:CIN3 ratios = 1.08, 2.11 and 1.47, respectively). Other HR types accounted for important proportions of HPV-positive CIN2 and CIN3, but their contribution dropped in ICC, with ICC:normal ratios ranging from 0.94 for HPV33 down to 0.16 for HPV51. ICC:normal ratios were particularly high for HPV45 in Africa (1.85) and South/Central America (1.79) and for HPV58 in Eastern Asia (1.36). ASCUS and LSIL appear proxies of HPV infection rather than cancer precursors, and even CIN3 is not entirely representative of the types causing ICC. HPV16 in particular, but also HPV18 and 45, warrant special attention in HPV-based screening programs. PMID:22323075
Guan, Peng; Howell-Jones, Rebecca; Li, Ni; Bruni, Laia; de Sanjosé, Silvia; Franceschi, Silvia; Clifford, Gary M
Background Human papillomaviruses (HPV) are the causative agents of cervical cancer in women, which results in over 250 000 deaths per year. Presently there are two prophylactic vaccines on the market, protecting against the two most common high-risk HPV types 16 and 18. These vaccines remain very expensive and are not generally affordable in developing countries where they are needed most. Additionally, there remains a need to treat women that are already infected with HPV, and who have high-grade lesions or cervical cancer. Methods In this paper, we characterize the immunogenicity of a therapeutic vaccine that targets the E7 protein of the most prevalent high-risk HPV - type 16 – the gene which has previously been shown to be effective in DNA vaccine trials in mice. The synthetic shuffled HPV-16 E7 (16E7SH) has lost its transforming properties but retains all naturally-occurring CTL epitopes. This was genetically fused to Zera®, a self-assembly domain of the maize ?-zein able to induce the accumulation of recombinant proteins into protein bodies (PBs), within the endoplasmic reticulum in a number of expression systems. Results High-level expression of the HPV 16E7SH protein fused to Zera® in plants was achieved, and the protein bodies could be easily and cost-effectively purified. Immune responses comparable to the 16E7SH DNA vaccine were demonstrated in the murine model, with the protein vaccine successfully inducing a specific humoral as well as cell mediated immune response, and mediating tumour regression. Conclusions The fusion of 16E7SH to the Zera® peptide was found to enhance the immune responses, presumably by means of a more efficient antigen presentation via the protein bodies. Interestingly, simply mixing the free PBs and 16E7SH also enhanced immune responses, indicating an adjuvant activity for the Zera® PBs.
Background Human papillomaviruses (HPV) are the aetiological agents of certain benign and malignant tumours of skin and mucosae; the most important of which is cervical cancer. Also, the incidence of ano-genital warts, HPV-anal cancer and oropharyngeal cancers are rising. To help ascertain a useful PCR detection protocol for oropharyngeal cancers, we directly compared three commonly used primer sets in detection of HPV from different clinical samples. Methods We compared PGMY09/11, MY09/11 and GP5+/6+ primers sets in PCRs of 34 clinically diagnosed samples of genital warts, cervical brushings (with associated histological diagnosis) and vulval biopsies. All negative samples were subsequently tested using the previously reported PGMY/GP PCR method and amplicons directly sequenced for confirmation and typing. An optimised PCR protocol was then compared to a line blot assay for detection of HPV in 15 oropharyngeal cancer samples. Results PGMY09/11 primers detected HPV presence in more cervical brushing (100%) and genital wart (92.9%) samples compared to MY09/11 (90% and 64.3%) and GP5+/6+ (80% and 64.3%) primer sets, respectively. From vulval biopsies, HPV detection rates were: MY09/11 (63.6%), GP5+/6+ (54.5%) and PGMY09/11 (54.5%). PGMY/GP nested PCR demonstrated that HPV was present, and direct sequencing confirmed genotypes. This nested PCR protocol showed detection of HPV in 10/15 (66.7%) of oropharyngeal cancer samples. Conclusions PGMY09/11 primers are the preferred primer set among these three for primary PCR screening with different clinical samples. MY09/11 and GP5+/6+ may be used (particularly for cervical samples) but demonstrate lower detection rates. A nested PCR approach (i.e. a PGMY-GP system) may be required to confirm negativity or to detect low levels of HPV, undetectable using current primary PCR methods, as demonstrated using oropharyngeal cancer samples.
The induction of mucosal immune responses in the genital tract may be important for increasing the effectiveness of vaccines for sexually transmitted infections (STIs). In this study, we asked whether direct immunization of the mouse genital tract with a non-replicating virus-like particle (VLP)-based vaccine could induce local mucosal as well as systemic antibody responses. Using VLPs derived from two bacteriophages, Q? and PP7, and from a mammalian virus that normally infects the genital tract, human papillomavirus (HPV), we show that intravaginal aerosol administration of VLPs can induce high titer IgG and IgA antibodies in the female genital tract as well as IgG in the sera. Using a mouse model for HPV infection, we show that intravaginal immunization with either HPV type 16 VLPs or with PP7 bacteriophage VLPs displaying a peptide derived from the HPV minor capsid protein L2 could protect mice from genital infection with an HPV16 pseudovirus. These results provide a general method for inducing genital mucosal and systemic antibody responses using VLP-based immunogens.
Hunter, Zoe; Tumban, Ebenezer; Dziduszko, Agnieszka; Chackerian, Bryce
A vaccine comprising human papillomavirus type 16 (HPV16) L2, E6 and E7 in a single tandem fusion protein (termed TA-CIN) has the potential advantages of both broad cross-protection against HPV transmission through induction of L2 antibodies able to cross neutralize different HPV types and of therapy by stimulating T cell responses targeting HPV16 early proteins. However, patients vaccinated with TA-CIN alone develop weak HPV neutralizing antibody and E6/E7-specific T cell responses. Here we test TA-CIN formulated along with the adjuvant GPI-0100, a semi-synthetic quillaja saponin analog that was developed to promote both humoral and cellular immune responses. Subcutaneous administration to mice of TA-CIN (20 microg) with 50microg GPI-0100, three times at biweekly intervals, elicited high titer HPV16 neutralizing serum antibody, robust neutralizing titers for other HPV16-related types, including HPV31 and HPV58, and neutralized to a lesser extent other genital mucosatropic papillomaviruses like HPV18, HPV45, HPV6 and HPV11. Notably, vaccination with TA-CIN in GPI-0100 protected mice from cutaneous HPV16 challenge as effectively as HPV16 L1 VLP without adjuvant. Formulation of TA-CIN with GPI-0100 enhanced the production of E7-specific, interferon gamma producing CD8(+) T cell precursors by 20-fold. Vaccination with TA-CIN in GPI-0100 also completely prevented tumor growth after challenge with 5x10(4) HPV16-transformed TC-1 tumor cells, whereas vaccination with TA-CIN alone delayed tumor growth. Furthermore, three monthly vaccinations with 125 microg of TA-CIN and 1000 microg GPI-0100 were well tolerated by pigtail macaques and induced both HPV16 E6/E7-specific T cell responses and serum antibodies that neutralized all HPV types tested. PMID:19095032
Karanam, Balasubramanyam; Gambhira, Ratish; Peng, Shiwen; Jagu, Subhashini; Kim, Dae-Jin; Ketner, Gary W; Stern, Peter L; Adams, Robert J; Roden, Richard B S
Background Two clinically relevant high-risk HPV (HR-HPV) types 16 and 18 are etiologically associated with the development of cervical carcinoma and are also reported to be present in many other carcinomas in extra-genital organ sites. Presence of HPV has been reported in breast carcinoma which is the second most common cancer in India and is showing a fast rising trend in urban population. The two early genes E6 and E7 of HPV type 16 have been shown to immortalize breast epithelial cells in vitro, but the role of HPV infection in breast carcinogenesis is highly controversial. Present study has therefore been undertaken to analyze the prevalence of HPV infection in both breast cancer tissues and blood samples from a large number of Indian women with breast cancer from different geographic regions. Methods The presence of all mucosal HPVs and the most common high-risk HPV types 16 and 18 DNA was detected by two different PCR methods - (i) conventional PCR assays using consensus primers (MY09/11, or GP5+/GP6+) or HPV16 E6/E7 primers and (ii) highly sensitive Real-Time PCR. A total of 228 biopsies and corresponding 142 blood samples collected prospectively from 252 patients from four different regions of India with significant socio-cultural, ethnic and demographic variations were tested. Results All biopsies and blood samples of breast cancer patients tested by PCR methods did not show positivity for HPV DNA sequences in conventional PCRs either by MY09/11 or by GP5+/GP6+/HPV16 E6/E7 primers. Further testing of these samples by real time PCR also failed to detect HPV DNA sequences. Conclusions Lack of detection of HPV DNA either in the tumor or in the blood DNA of breast cancer patients by both conventional and real time PCR does not support a role of genital HPV in the pathogenesis of breast cancer in Indian women.
Background The association between human papillomavirus (HPV) infection and non-melanoma skin cancers (NMSCs) such as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) is not yet fully understood. We analysed the prevalence and spectrum of cutaneous beta-HPV types and mucosal/genital HPV types in paired biopsies (tumour and corresponding perilesional skin) obtained from 50 BCC immunocompetent patients. A small group of SCC patients (n=9) was also included. We also evaluated some previously postulated risk factors for HPV infection in NMSC patients. Results All biopsies were negative for mucosal/genital HPV types. Overall, beta-HPV DNA was detected more often in SCC compared to BCC patients (78% vs 55% of total samples). The frequency of infection increased with the patient’s age [OR=4.88 (95% CI 1.29-18.39)]. There was no significant correlation between beta-HPV positivity and sex, skin type and UV exposure. The prevalence of beta-HPV species 1 types was significantly higher than those belonging to other beta-HPV species in biopsies from BCC (p=0.022) but not from SCC subjects (p=0.091). There was no significant difference in the overall prevalence of beta-HPV infection and the number of viral types between tumour lesions and perilesional skin. BCC samples were significantly more likely to be infected with beta-HPV species 1 types compared to perilesional skin (p=0.036) and showed a higher frequency of mixed infections (p=0.028). Conclusions These findings demonstrate that beta-HPV types belonging to species 1 are the most common HPV types detected in the skin of BCC patients. Moreover beta-1-HPV types and mixed infections are significantly more frequent in tumour samples than in healthy perilesional skin. Our results suggest that beta-1-HPVs as well as co-infection with more than one viral type could be important in NMSC and in particular in BCC. Further studies aimed to compare the biological activity of viral types in tumours and in healthy skin (viral replication and expression, interference of infection with cellular functions) are necessary to understand the role of HPV infection in skin cancer.
Counseling patients about any sexually transmitted disease (STD) is difficult, for both the physician and the patient, but a diagnosis of genital warts presents particular challenges. For many patients, being told that they have any STD comes as a shock. Although fear is a common reaction, the relationship between human papillomavirus (HPV) and cancer has made the presence of genital
We compared the measurement of human papillomavirus (HPV)-specific serum antibody levels with the virus-like-particle multiplex immunoassay (VLP-MIA), competitive Luminex immunoassay (cLIA), and glutathione S-transferase (GST) L1-based MIA. Using a large panel of serum samples, these assays showed mutually good correlations for both naturally induced and vaccine-derived HPV-specific antibody levels. However, an adaptation of the GST L1-based MIA resulted in an improved correlation with both cLIA and VLP-MIA.
Schepp, Rutger M.; Mollers, Madelief; Mooij, Sofie H.; Meijer, Chris J. L. M.; Berbers, Guy A. M.; van der Klis, Fiona R. M.
We compared the measurement of human papillomavirus (HPV)-specific serum antibody levels with the virus-like-particle multiplex immunoassay (VLP-MIA), competitive Luminex immunoassay (cLIA), and glutathione S-transferase (GST) L1-based MIA. Using a large panel of serum samples, these assays showed mutually good correlations for both naturally induced and vaccine-derived HPV-specific antibody levels. However, an adaptation of the GST L1-based MIA resulted in an improved correlation with both cLIA and VLP-MIA. PMID:23740920
Scherpenisse, Mirte; Schepp, Rutger M; Mollers, Madelief; Mooij, Sofie H; Meijer, Chris J L M; Berbers, Guy A M; van der Klis, Fiona R M
Background This multicenter study describes the type-specific prevalence of HPV infection in the general population from central and southern Italy, comparing the data with previously published Italian studies. Methods Women aged from 25 to 65 who attended cervical cancer screening in five different Italian regions were tested for HPV infection with Hybrid Capture II (HCII) low and high risk probes. Women repeating Pap-test upon unsatisfactory or positive results, or as a post-treatment and post-colposcopy follow-up analysis, were excluded from our study. High risk (HR) HPV positive samples were typed using GP5+/GP6+ primed PCR, followed by Reverse Line Blot for 18 high/intermediate risk HPV types, while low risk (LR) HPV positive samples were tested with type specific primers for HPV6 and HPV11. Results 3817 women had a valid HCII test: 350 of them (9.2%) were positive for HR probes, 160 (4.2%) for LR probes, while 57 women were positive for both. Multiple infections were detected in 97 HR HPV positive women. The most common types were HPV 16 (3%), 31 (1.2%), 51 (1%). HPV6 ranked fifth (0.6%), HPV18 ranked tenth (0.5%) and HPV11 sixteenth (0.3%). In Sardinia the prevalence of high-risk infection was 13%, significantly higher than the mean value (p < 0.00005). The distribution of the most frequent types did not significantly differ by centre (p = 0.187) and age (p = 0.085). Conclusions Because cervical cancer incidence and Pap test coverage is lower in southern than in northern Italy, a lower prevalence of high-risk infections in the general population was expected in the south. However, prevalence detected in this study for the south of the country is slightly but significantly higher than the rest of Italy. The consequence may be an epidemic of cervical cancer in the next decades if adequate screening programs are not implemented there.
Background Epidemiological studies on genital human papilloma viruses infection (HPVs) in general population are crucial for the implementation of health policy guidelines for developing the strategies to prevent the primary and secondary cervical cancer. In different parts of Iran, there is a lack of population-based studies to determine the prevalence of HPV in the general population. The aim of this population-based study is to compare the prevalence rate of genital HPV infection among reproductive women with our previous clinic-based data, which showed a prevalence rate of 5% in women in southern Iran. Results Using general primers for all genotypes of HPV, of 799 randomly selected women, five (0.63%, 95% CI 0.23-1.55%) tested positive for HPV DNA. Overall, seven different HPV genotypes were detected: six types (16, 18, 31, 33, 51 and 56) were carcinogenic, or “high risk genotypes” and one genotype (HPV-66) was “probably carcinogenic.” Conclusions In a population-based study, the prevalence of HPV infection among southern Iranian women was lower than that observed worldwide. However, our gynaecological clinic-based study on the prevalence of HPV infection showed results comparable with other studies in the Middle East and Persian Gulf countries. Since gynaecological clinic-based data may generally overestimate HPV prevalence, estimates of prevalence according to clinic-based data should be adjusted downward by the population-based survey estimates.
The EUROGIN 2011 roadmap reviews the current burden of HPV (human papillomavirus)-related morbidity, as well as the evidence and potential practice recommendations regarding primary and secondary prevention and treatment of cancers and other disease associated with HPV infection. HPV infection causes approximately 600,000 cases of cancer of the cervix, vulva, vagina, anus and oropharynx annually, as well as benign diseases such as genital warts and recurrent respiratory papillomatosis. Whereas the incidence of cervical cancer has been decreasing over recent decades, the incidence of anal and oropharyngeal carcinoma, for which there are no effective screening programs, has been rising over the last couple of decades. Randomised trials have demonstrated improved efficacy of HPV-based compared to cytology-based cervical cancer screening. Defining the best algorithms to triage HPV-positive women, age ranges and screening intervals are priorities for pooled analyses and further research, whereas feasibility questions can be addressed through screening programmes. HPV vaccination will reduce the burden of cervical precancer and probably also of invasive cervical and other HPV-related disease in women. Recent trials demonstrated that prophylactic vaccination also protects against anogenital HPV infection, ano-genital intraepithelial lesions and warts associated with vaccine types, in males; and anal HPV infection and anal intraepithelial neoplasia in MSM. HPV-related oropharyngeal cancer could be treated less aggressively because of better survival compared to cancers of the oropharynx unrelated to HPV. Key findings in the field of cervical cancer prevention should now be translated in cost-effective strategies, following an organised approach integrating primary and secondary prevention, according to scientific evidence but adapted to the local situation with particular attention to regions with the highest burden of disease.
Arbyn, Marc; de Sanjose, Silvia; Saraiya, Mona; Sideri, Mario; Palefsky, Joel; Lacey, Charles; Gillison, Maura; Bruni, Laia; Ronco, Guglielmo; Wentzensen, Nicolas; Brotherton, Julia; Qiao, You-Lin; Denny, Lynnette; Bornstein, Jacob; Abramowitz, Laurent; Giuliano, Anna; Tommasino, Massimo; Monsonego, Joseph
Background: Knowledge of the prevalence of type-specific human papillomavirus (HPV) infections is necessary to predict the expected, and to monitor the actual, impact of HPV immunisation and to design effective screening strategies for vaccinated populations. Methods: Residual specimens of cervical cytology (N=4719), CIN3/CGIN and cervical cancer biopsies (N=1515) were obtained from sites throughout England, anonymised and tested for HPV DNA using the Linear Array typing system (Roche). Results: The prevalence of HPV 16 and/or 18 (with or without another high-risk (HR) type) was 76% in squamous cell carcinomas, 82% in adeno/adenosquamous carcinomas and 63% and 91% in CIN3 and CGIN, respectively. Of all HR HPV-infected women undergoing cytology, non-vaccine HPV types only were found in over 60% of those with mild dyskaryosis or below, and in <20% of those with cancer. In women of all ages undergoing screening, HR HPV prevalence was 16% and HPV 16 and/or 18 prevalence was 5%. Conclusion: Pre-immunisation, high-grade cervical disease in England was predominantly associated with HPV 16 and/or 18, which promises a high impact from HPV immunisation in due course. Second-generation vaccines and screening strategies need to consider the best ways to detect and prevent disease due to the remaining HR HPV types.
Howell-Jones, R; Bailey, A; Beddows, S; Sargent, A; de Silva, N; Wilson, G; Anton, J; Nichols, T; Soldan, K; Kitchener, H
The relative and analytical sensitivity of the APTIMA HPV test (AHPV, broad-spectrum, target amplification) and the PreTect HPV-Proofer (type-specific, target amplification) for the detection of HPV mRNA in various cell lines was compared. Equivalent relative sensitivity for the HPV 16-containing cell lines (2.5 cells/ml with both CaSki and SiHa) was observed for the mRNA assays--and similar sensitivities were observed for the detection of HPV 18 (HeLa) and 45 (MS751); ranging from 2.5 cells/ml (Proofer) to 25 cells/ml (APTIMA). In relation to analytical sensitivity, again, the mRNA assays showed similar sensitivities to each other, ranging from 0.1 to 1 cell per reaction for APTIMA and 0.1 to 10 cells per reaction for PreTect HPV-Proofer (depending on cell line). Both mRNA assays consistently achieved a higher analytical sensitivity than a DNA based comparator--the Hybrid Capture 2 High-Risk HPV DNA test (hc2). This study indicates that mRNA tests had high analytical sensitivity, higher than a well established DNA-test based when using cell lines as target. Implications for clinical application are discussed. PMID:23727117
Cuschieri, Kate; Hardie, Alison; Hovland, Siri; Hoaas, Bente; Karlsen, Frank; Cubie, Heather
Genital Herpes, which is caused by Herpes Simplex Virus-1 or -2 (HSV-1, -2, predominantly HSV-2) is a sexually transmitted infection (STI) that causes a chronic latent infection with outbreak episodes linked to transmission. Antiviral therapies are effective in reducing viral shedding during these episodes, but are ineffective as a whole since many outbreaks are asymptomatic or have mild symptoms. Thus, the development of a vaccine for genital herpes is needed to control this disease. The question of how to implement such a vaccine program is an important one, and may be similar to the vaccination program for Human Papilloma Virus (HPV) for young females. We have developed a mathematical model to describe the epidemiology of vaccination targeting young females against HSV-2. The model population is delineated with respect to age group, sexual activity and infection status including oral infection of HSV-1, which may affect vaccine efficacy. A threshold parameter R(C), which determines the level of vaccine uptake needed to eradicate HSV-2, is found. Computer simulation shows that an adolescent-only vaccination program may be effective in eliminating HSV-2 disease, however, the success of extinction greatly depends on the level of vaccine uptake, the vaccine efficacy, the age of sexual maturity and safe sex practices. However, the time course of eradication would take many years. We also investigate the prevalence of infection in the total population and in women between 16-30 years of age before and after vaccination has been introduced, and show that the adolescent-only vaccination program can be effective in reducing disease prevalence in these populations depending on the level of vaccine uptake and vaccine efficacy. This will also result in a decrease of maternal-fetal transmission of HSV-2 infection. Another important, if commonsense, conclusion is that vaccination of some females reduces infection in men, which then reduces infection in women. PMID:23071536
Lou, Yijun; Qesmi, Redouane; Wang, Qian; Steben, Marc; Wu, Jianhong; Heffernan, Jane M
Summary. The virulence of transparent (Tr) and opaque (Op) colony types of Neisseria gonorrhoeae in the genital tract of female mice was evaluated at two stages of oestrous. Isogenic pairs of Tr and Op variants were isolated from N. gonorrhoeae strain 57-120. Both variants exhibited a T2 morphology, but only the Op variant possessed protein I1 (P. 11) in outer-membrane
E. Kita; N. Katsui; M. Emoto; M. Sawaki; D. Oku; FUMIKO NISHIKAWA; AKIKO HAMURO; S. Kashiba
Aims Persistent infection indicated by detection of human papillomavirus 16 (HPV-16) on repeat testing over a period of time poses the greatest cervical cancer risk. However, variants of HPV-16, HPV-31 and HPV-33 may share several short sequence homologies in the hypervariable L1 gene commonly targeted for HPV genotyping. The purpose of this study was to introduce a robust laboratory procedure to validate HPV-16 detected in clinical specimens, using the GenBank sequence database as the standard reference for genotyping. Methods A nested PCR with two pairs of consensus primers was used to amplify the HPV DNA released in crude proteinase K digest of the cervicovaginal cells in liquid-based Papanicolaou cytology specimens. The positive nested PCR products were used for direct automated DNA sequencing. Results A 48-base sequence downstream of the GP5+ priming site, or a 34-base sequence upstream thereof, was needed for unequivocal validation of an HPV-16 isolate. Selection of a 45-base, or shorter, sequence immediately downstream of the GP5+ site for Basic Local Alignment Search Tool sequence analysis invariably led to ambiguous genotyping results. Conclusions DNA sequence analysis may be used for differential genotyping of HPV-16, HPV-31 and HPV-33 in clinical specimens. However, selection of the signature sequence for Basic Local Alignment Search Tool algorithms is crucial to distinguish certain HPV-16 variants from other closely related HPV genotypes.
Vigliotti, Veronica S; Pappu, Suri
UV exposure and p53 mutations are major factors in non-melanoma skin cancer, whereas a role for HPV infections has not been defined. Previous data demonstrated the wtp53-mediated degradation of cutaneous HPV20E6 by caspase-3. ?Np63? and hot-spot mutant p53R248W conveyed a protective effect on HPV20E6 under these conditions. We demonstrate a differential regulation by wtp53 of the E6 genes of cutaneous types HPV4, HPV5, HPV7, HPV27, HPV38, HPV48, HPV60 and HPV77. Caspase- or proteasome-mediated down-regulation was HPV type dependent. Mutant p53R248W up-regulated expression of all these E6 proteins as did ?Np63? except for HPV38E6 which was down-regulated by the latter. None of these cellular proteins affected HPV41E6 expression. Ectopic expression of both mutp53R248W and ?Np63? in the normal NIKS keratinocyte cell line harbouring endogenous p53 and p63however led to a down-regulation of HPV20E6. We demonstrate that HPV20E6 expression in these cells is modulated by additional, yet unidentified, cellular protein(s), which are not necessarily involved in apoptosis or autophagy. We further demonstrate proliferation of HPV20E6-expressing keratinocytes. Levels of proteins involved in cell cycle control, cyclin-D1, cdk6 and p16INK4a, phosphorylated pRB, as well as c-Jun and p-c-Jun, were all increased in these cells. HPV20E6 did not compete for the interaction between p16INK4a with cyclin-D1 or cdk6. Phosphorylation of pRB in the HPV20E6 expressing cells seems to be sufficient to override the cytokenetic block induced by the p16INK4a/pRB pathway. The present study demonstrates the diverse influence of p53 family members on individual cutaneous HPVE6 proteins. HPV20E6 expression also resulted in varying protein levels of factors involved in proliferation and differentiation.
Fei, Jian-Wei; de Villiers, Ethel-Michele
This study compares the type-specific human papillomavirus (HPV) DNA test with E6/E7 mRNA detection assay because of their importance in cervical cancer screening programs. A total of 105 women with positive high-risk Hybrid Capture 2 or Abbott RealTime High Risk HPV screening test and an abnormal cervical Pap smear were enrolled in the study. HPV typing was performed by multiplex real-time PCR (HPV High Risk Typing Real-TM test). HPV-16, 18, 31, 33, and 45 E6/E7 mRNAs were determined by type-specific real-time NASBA assay (NucliSENS EasyQ HPV v1.1). Infections caused by HPV-16, 18, 31, 33, and 45 types increased with severity of cervical cytology (p=0.008). Global positivity of five HPV E6/E7 mRNAs was lower than DNA positivity within women with atypical squamous cells of undetermined significance (p=0.016; p=0.008). High agreement of the tests was found in the groups of women with low-grade (p=1.000; p=0.063) and high-grade squamous intraepithelial lesion (p=0.250; p=0.125). Type-specific agreement of both diagnostic approaches was high regardless of cytology. Based on the found differences between HPV-16, 18, 31, 33, and 45 E6/E7 mRNA and DNA positivity, further study is needed to test the role of mRNA testing in the triage of women with atypical squamous cells of undetermined significance in Pap smear. PMID:24036071
Salimovi?-Beši?, Irma; Tomi?-?i?a, Anja; Smailji, Admir; Huki?, Mirsada
External genital warts, also known as condylomata acuminata, are extremely common, with between 500,000 to one million new cases diagnosed each year in the United States alone. To date, more than 120 distinct subtypes of human papillomavirus have been identified. Human papillomavirus types 6 and 11 rarely give rise to cervical cancers, but are responsible for 90 percent of the cases of genital warts. The current treatment options are largely centered upon removal of the warts rather than elimination of the underlying viral infection. A wide range of therapies are presently in use, which are highly variable and can differ dramatically with respect to cost, side-effect profiles, dosing schedules, duration of treatment, and overall effectiveness. As of yet, no definitive therapy has emerged as the ideal standard of care in the treatment of genital warts, and therapy selection generally occurs in a patient-specific manner.
Yanofsky, Valerie R.; Patel, Rita V.
Human papillomavirus (HPV) infections are causally related to cervical cancer and a range of other diseases, both in adults and in minors. Information on the frequency of genital HPV infections in adolescents is sparse. The aim of this study was to gain insight into the genotype-specific distribution of HPV genotypes in patients younger than 18 years of age. This observational retrospective study included 4807 samples of patients presenting for opportunistic screening in Belgium between June 2006 and January 2012. For statistical analysis, only the first visits of patients were withheld, reducing the sample to 4180. Samples were collected in liquid-based cytology medium and analyzed using a series of genotype-specific real-time PCR reactions. Cytology was read with previous knowledge of HPV infection and scored using the Bethesda classification. The mean age was 16.9 years. Most youngsters had no complaints (88.4%), were using hormonal contraception (79.5%), and clinical examination did not show any abnormalities (96.0%). The overall HPV frequency was 15.7%, with the most frequently found types being HPV16 (16.7%), HPV51 (14.6%), HPV66 (10.4%), HPV31 (9.9%), and HPV39 (9.1%). More than one-third (39.0%) of the infected girls harbored an infection with at least two HPV genotypes. Cytological abnormalities were found in 8.2% of samples. L-SIL (4.2%) was most frequently observed, followed by ASC-US (3.6%), HSIL (0.3%), and ASC-H (0.1%). The severity of lesions worsened with increasing age. Our findings indicate that an aberrant HPV genotype profile can be found in adolescent girls; moreover, this group shows a high rate of cervical abnormalities. PMID:24858715
Merckx, Mireille; Benoy, Ina; Meys, Joris; Depuydt, Christophe; Temmerman, Marleen; Weyers, Steven; Vanden Broeck, Davy
The majority of vulvar intraepithelial neoplasia (VIN) is high-grade and is related to high-risk human papillomavirus (HRHPV) (most commonly HPV 16). It is considered to be the precursor of HRHPV-related vulvar squamous cell carcinoma. Vulvar condyloma acuminatum is low-risk HPV (LRHPV)-related (most commonly types 6 and 11) and has virtually no risk of neoplastic progression. While infection with multiple LRHPV and HRHPV types has been reported for cervical squamous intraepithelial lesions, coexisting vulvar condyloma and adjacent high-grade VIN have not been well characterized. Eleven cases of concurrent condyloma acuminatum and adjacent flat high-grade VIN and 3 cases of high-grade VIN with prominent condylomatous architecture were analyzed using immunohistochemical analysis of p16 expression, in situ hybridization (ISH) for HPV detection [HPV 6/11, HPV 16, HPV 18, and HPV wide spectrum (types 6, 11, 16, 18, 31, 33, 35, 45, 51, 52) probes], and HPV typing by a polymerase chain reaction (PCR)-based method (in select cases). All patients had underlying immunosuppressive conditions (human immunodeficiency virus infection or posttransplant therapy). Among the 11 cases of concurrent high-grade VIN and condyloma, the lesions were directly adjacent to one another in 5 cases (with 2 of these demonstrating an intimate admixture of lesions), and in 6 cases the lesions were found in separate tissue sections from the same specimen. Diffuse/strong p16 expression was seen in all high-grade VIN lesions, whereas patchy/weak staining was found in all condylomata. All condylomata contained HPV 6 or 11 as detected by ISH. HRHPV was detected in all of the accompanying high-grade VIN lesions. Ten contained HPV 16 (9 by ISH, 1 by PCR), with the remaining case containing multiple HPV types by PCR. All condylomatous high-grade VIN lesions demonstrated diffuse/strong p16 expression and had evidence of HRHPV (1 with HPV 16 by ISH, 1 with HPV 18 by ISH, and 1 with multiple HPV types by PCR), with no detection of HPV 6 or 11 by ISH. The restriction of LRHPV to condylomatous components and HRHPV to high-grade VIN components of adjacent lesions suggests these are independent lesions caused by different HPV types. Diffuse p16 expression can highlight small foci of high-grade VIN, which may be overlooked in more abundant condylomatous tissue from immunosuppressed patients. The presence of only HRHPV in those VIN lesions with high-grade cytologic features but prominent condylomatous architecture supports their classification as forms of pure high-grade VIN and distinguishes them from condyloma acuminatum. PMID:23026935
Maniar, Kruti P; Ronnett, Brigitte M; Vang, Russell; Yemelyanova, Anna
Herpes simplex virus (HSV)-2 is the principal agent of chronic remittent genital herpes. Worldwide, only 10–20% of genital isolates are HSV-1. Studies from the British Isles and Scandinavia indicate, however, that HSV-1 is responsible for a significant proportion or even the majority of first clinical episodes of genital herpes in young women. Actual data show that a trend towards genital
Lars Lippelt; Rüdiger W. Braun; Joachim E. Kühn
Purpose ‘Praneem’, a polyherbal formulation developed by us, has successfully completed Phase II efficacy study for treatment of abnormal\\u000a vaginal discharge due to reproductive tract infections that act as co-factors for HPV persistence. In the present study we\\u000a evaluated potential anti-HPV activity of Praneem in women infected with high risk HPV type 16.\\u000a \\u000a \\u000a \\u000a Methods Twenty women molecularly diagnosed positive for HPV16 infection
Shirish Shukla; Alok C. Bharti; Showket Hussain; Sutapa Mahata; Suresh Hedau; Uma Kailash; Veena Kashyap; Suresh Bhambhani; Meera Roy; Swaraj Batra; G. P. Talwar; Bhudev C. Das
Infection with genital human papillomavirus (HPV) may cause anogenital cancers, oropharyngeal cancers, anogenital warts, and respiratory papillomas. Two prophylactic vaccines (a bivalent and a quadrivalent vaccine) are now licensed and currently in use in a number of countries. Both vaccines prevent infection with HPV-16 and HPV-18, which together cause approximately 70% of cervical cancers, and clinical trials have demonstrated 90%-100% efficacy in preventing precancerous cervical lesions attributable to HPV-16 and HPV-18. One vaccine also prevents HPV-6 and HPV-11, which cause 90% of genital warts. A growing literature describes associations between psychosocial, interpersonal, organizational, and societal factors that influence HPV vaccination acceptability. This paper summarizes the current literature and presents an integrated perspective, taking into account these diverse influences. The resulting integrated model can be used as a heuristic tool for organizing factors at multiple levels to guide intervention development and future research.
Fernandez, Maria E.; Allen, Jennifer D.; Mistry, Ritesh; Kahn, Jessica A.
The EUROGIN 2011 roadmap reviews the current burden of human papillomavirus (HPV)-related morbidity, as well as the evidence and potential practice recommendations regarding primary and secondary prevention and treatment of cancers and other disease associated with HPV infection. HPV infection causes ~600,000 cases of cancer of the cervix, vulva, vagina, anus and oropharynx annually, as well as benign diseases such as genital warts and recurrent respiratory papillomatosis. Whereas the incidence of cervical cancer has been decreasing over recent decades, the incidence of anal and oropharyngeal carcinoma, for which there are no effective screening programs, has been rising over the last couple of decades. Randomized trials have demonstrated improved efficacy of HPV-based compared to cytology-based cervical cancer screening. Defining the best algorithms to triage HPV-positive women, age ranges and screening intervals are priorities for pooled analyses and further research, whereas feasibility questions can be addressed through screening programs. HPV vaccination will reduce the burden of cervical precancer and probably also of invasive cervical and other HPV-related disease in women. Recent trials demonstrated that prophylactic vaccination also protects against anogenital HPV infection, anogenital intraepithelial lesions and warts associated with vaccine types, in males; and anal HPV infection and anal intraepithelial neoplasia in MSM. HPV-related oropharyngeal cancer could be treated less aggressively because of better survival compared to cancers of the oropharynx unrelated to HPV. Key findings in the field of cervical cancer prevention should now be translated in cost-effective strategies, following an organized approach integrating primary and secondary prevention, according to scientific evidence but adapted to the local situation with particular attention to regions with the highest burden of disease. PMID:22623137
Arbyn, Marc; de Sanjosé, Silvia; Saraiya, Mona; Sideri, Mario; Palefsky, Joel; Lacey, Charles; Gillison, Maura; Bruni, Laia; Ronco, Guglielmo; Wentzensen, Nicolas; Brotherton, Julia; Qiao, You-Lin; Denny, Lynnette; Bornstein, Jacob; Abramowitz, Laurent; Giuliano, Anna; Tommasino, Massimo; Monsonego, Joseph
We determined the utility of an assay for 13 cancer-associated HPV types in primary cervical cancer screening of Zimbabwe women at high risk of HIV infection. HIV antibody status was determined by ELISA of oral mucosal specimens, and HPV DNA in the genital tract was identified by hybridization of cervical scrapes with probe B of Hybrid Capture II. Among the 466 women investigated, the prevalence of HPV, low-grade squamous intraepithelial lesions (LGSIL) and high-grade SIL (HGSIL) were 47.2%, 13.9% and 12%. Fifty-three and one-half percent of the women were HIV-seropositive. As compared with HIV-seronegative women, HIV-infected women had a greater than 2-fold HPV prevalence (64.3% vs. 27.6%), a greater than 7-fold amount of HPV DNA (RLU of 82.6 vs. 10.7) in HPV(+) women assessed as normal on the reference standard, and a nearly 3-fold greater HGSIL prevalence (17.3% vs. 5.9%). The strong link between HGSIL and HPV DNA positivity was seen in both HIV-infected and HIV-seronegative women. The amount of HPV DNA increased with disease severity in both HIV-seronegative and HIV-infected women. The sensitivity and specificity of the HPV test for HGSIL were, respectively, 90.7% (95% confidence limit 77.9-97.4%) and 41.3% (34.5-48.3%) in HIV-infected women and 61.5% (31.6-86.1%) and 74.5% (68.0-80.3%), respectively, in HIV(-) women. The usefulness of the HPV test as a screening test for cervical cancer in areas of high HPV prevalence will depend upon local health resource availability, disease priorities and policies regarding clinical case management. PMID:10629079
Womack, S D; Chirenje, Z M; Gaffikin, L; Blumenthal, P D; McGrath, J A; Chipato, T; Ngwalle, S; Munjoma, M; Shah, K V
Inclusion of the benefits of enhanced cross-protection against cervical cancer and prevention of genital warts in the cost-effectiveness analysis of human papillomavirus vaccination in the Netherlands
Background Infection with HPV 16 and 18, the major causative agents of cervical cancer, can be prevented through vaccination with a bivalent or quadrivalent vaccine. Both vaccines provide cross-protection against HPV-types not included in the vaccines. In particular, the bivalent vaccine provides additional protection against HPV 31, 33, and 45 and the quadrivalent vaccine against HPV31. The quadrivalent vaccine additionally protects against low-risk HPV type 6 and 11, responsible for most cases of genital warts. In this study, we made an analytical comparison of the two vaccines in terms of cost-effectiveness including the additional benefits of cross-protection and protection against genital warts in comparison with a screening-only strategy. Methods We used a Markov model, simulating the progression from HPV infection to cervical cancer or genital warts. The model was used to estimate the difference in future costs and health effects of both HPV-vaccines separately. Results In a cohort of 100,000 women, use of the bivalent or quadrivalent vaccine (both at 50% vaccination coverage) reduces the cervical cancer incidence by 221 and 207 cases, corresponding to ICERs of €17,600/QALY and €18,900/QALY, respectively. It was estimated that the quadrivalent vaccine additionally prevents 4390 cases of genital warts, reducing the ICER to €16,300/QALY. Assuming a comparable willingness to pay for cancer and genital warts prevention, the difference in ICERs could justify a slightly higher price (~7% per dose) in favor of the quadrivalent vaccine. Conclusions Clearly, HPV vaccination has been implemented for the prevention of cervical cancer. From this perspective, use of the bivalent HPV vaccine appears to be most effective and cost-effective. Including the benefits of prevention against genital warts, the ICER of the quadrivalent HPV vaccine was found to be slightly more favourable. However, current decision-making on the introduction of HPV is driven by the primary cervical cancer outcome. New vaccine tenders could consider the benefits of cross-protection and the benefits of genital warts, which requires more balanced decision-making.
Objective.Vulvar intraepithelial neoplasia (VIN) is a premalignant disease of the lower genital tract. The increased occurrence of high-risk human papillomavirus (HPV) infection seems to be associated with the increasing frequency of VIN. Integration of HPV DNA into host chromosome has been hypothesized to be a critical step in the carcinogenesis of cervical neoplasia resulting in altered expression of two viral
Peter Hillemanns; Xiuli Wang
Haemophilus influenzae (H. influenzae) type B a non-motile, aerobic, gram negative cocobacillus is a commensal of upper respiratory tract. Genitourinary infection due to H. influenzae has been reported but bacteremia associated with such infection appears to be rare. We report a case of 19 years young primigravida with complaints of amenorrhea of 32 weeks and 5 days, pyrexia, abdominal pain and blood stained discharge per vaginum. H. influenzae type B was recovered from the genital tract as well as blood of the mother indicating maternal septicemia. Septicemia caused by H. influenzae type B in pregnant women following vaginal colonization and infection is rare. It has been reported in many parts of world over the years; to the best of our knowledge this is the first reported case from Nepal. H. influenzae should be considered as a potential maternal, fetal, and neonatal pathogen.
Supram, Hosuru Subramanya; Gokhale, Shishir; Bhatta, Dharm Raj; Sharma, JSS; Shrestha, Junu
Background Cervical cancer is a major public health problem in Latin America and the Caribbean (LA&C), showing some of the highest incidence and mortality rates worldwide. Information on HPV type distribution in high-grade cervical lesions (HSIL) and invasive cervical cancer (ICC) is crucial to predict the future impact of HPV16/18 vaccines and screening programmes, and to establish an appropriate post-vaccinal virologic surveillance. The aim was to assess the prevalence of HPV types in HSIL and ICC in studies in LA&C. Methods and Findings We performed a systematic review, following the MOOSE guidelines for systematic reviews of observational studies, and the PRISMA statement for reporting systematic reviews and meta-analyses. Inclusion criteria were at least ten cases of HSIL/ICC, and HPV-type elicitation. The search, without language restrictions, was performed in MEDLINE, Cochrane Library, EMBASE, LILACS from inception date to December 2009, proceedings, reference lists and consulting experts. A meta-analysis was performed using arc-sine transformations to stabilize the variance of simple proportions. Seventy-nine studies from 18 countries were identified, including 2446 cases of HSIL and 5540 of ICC. Overall, 46.5% of HSIL cases harbored HPV 16 and 8.9% HPV18; in ICC, 53.2% of cases harbored HPV 16 and13.2% HPV 18. The next five most common types, in decreasing frequency, were HPV 31, 58, 33, 45, and 52. Study's limitations comprise the cross-sectional design of most included studies and their inherent risk of bias, the lack of representativeness, and variations in the HPV type-specific sensitivity of different PCR protocols. Conclusions This study is the broadest summary of HPV type distribution in HSIL and ICC in LA&C to date. These data are essential for local decision makers regarding HPV screening and vaccination policies. Continued HPV surveillance would be useful, to assess the potential for changing type-specific HPV prevalence in the post-vaccination era in Latin America.
Ciapponi, Agustin; Bardach, Ariel; Glujovsky, Demian; Gibbons, Luz; Picconi, Maria Alejandra
Background The incidence of cervical cancer in Paraguay is among the highest in the world, with the human papillomavirus (HPV) being a necessary factor for cervical cancer. Knowledge about HPV infection among indigenous women is limited. This cross-sectional study analyzed the frequency of HPV and other genital infections in indigenous Paraguayan women of the Department of Presidente Hayes. Methods This study included 181 sexually active women without cervical lesions. They belonged to the following ethnicities: Maká (n?=?40); Nivaclé (n?=?23); Sanapaná (n?=?33); Enxet Sur (n?=?51) and Toba-Qom (n?=?34). The detection of HPV and other gynecological infectious microorganisms was performed by either molecular methods (for Mycoplasma hominis, Ureaplasma urealyticum, Chlamydia trachomatis), gram staining and/or culture (for Gardnerella vaginalis, Candida sp, Trichomonas vaginalis, Neisseria gonorrhoeae), serological methods (for Treponema pallidum, human immunodeficiency virus [HIV]) or cytology (cervical inflammation). Results A high prevalence (41.4%) of women positive for at least one sexually transmitted infection (STI) was found (23.2% any-type HPV, 11.6% T pallidum, 10.5% T vaginalis, 9.9% C trachomatis and 0.6% HIV) with 12.2% having more than one STI. HPV infection was the most frequent, with 16.1% of women positive for high-risk HPV types. There was a statistically significant association observed between any-type HPV and C trachomatis (p?=?0.004), which indicates that the detection of one of these agents should suggest the presence of the other. There was no association between any-type HPV and other genital infections or cervical inflammation, suggesting that other mechanism could exist to favor infection with the virus. Conclusion This multidisciplinary work suggests that STIs are frequent, making it necessary to implement control measures and improve diagnosis in order to increase the number of cases detected, especially in populations with poor access to health centers.
Although many treatments are available for genital warts caused by human papillomavirus (HPV), none are uniformly successful in the treatment of this disease. Most current treatment options work by destroying affected tissue, either by a cytotoxic or a physically ablative mode of action. Interferons have antiviral, antiproliferative, and immunomodulatory activities, but these have not translated into a high level of
Background An increasing incidence of anal cancer among men, especially men who have sex with men (MSM) suggests a need to better understand anal human papillomavirus (HPV) infection among this group. Methods A cross-sectional study was conducted among MSM in Shenzhen, China. Blood was collected for HIV serological testing and syphilis serological screening, and anal swabs were collected for HPV genotyping. Difference of HPV prevalence between HIV seropositive and HIV seronegative MSM was assessed by chi-square test. Factors associated with anal canal HPV infection were assessed by univariate and multivariate logistic regression. Results A total of 408 MSM were recruited. HIV and HPV prevalence were 6.9% and 36.4%, respectively. HPV was detected in the anal canal in 71.4% of the HIV-positive MSM and in 33.8% of the HIV-negative MSM (P<0.001). Oncogenic types were seen more often in anal specimens of HIV-positive MSM than in specimens of HIV-negative MSM (P?=?0.001). The HPV genotypes detected most frequently were HPV06 (8.2%), HPV16 (7.2%), HPV11 (6.4%), HPV18 (4.7%), HPV58 (4.7%), and HPV52 (4.2%). Conclusions In this study, HIV positive MSM had a higher burden of HPV infection, especially oncogenic HPV infection. HPV types 52 and 58 were as popular as those types designed for the currently available vaccine (HPV6, 11, 16, 18).
Zhang, Dong-Yan; Yin, Yue-Ping; Feng, Tie-Jian; Hong, Fu-Chang; Jiang, Ning; Wang, Bao-Xi; Chen, Xiang-Sheng
Genital human papillomaviruses (HPVs) are commonly detected from clinical samples by consensus PCR methods. Two commonly used primer systems, the MY09-MY11 (MY09/11) primers and the GP5+-GP6+ (GP5+/6+) primers, amplify a broad spectrum of HPV genotypes, but with various levels of sensitivity among the HPV types. Analysis of the primer-target sequence homology for the MY09/11 primers showed an association between inefficient amplification of HPV types and the number and position of mismatches, despite accommodation of sequence variation by inclusion of degenerate base sites. The MY09/11 primers were redesigned to increase the sensitivity of amplification across the type spectrum by using the same primer binding regions in the L1 open reading frame. Sequence heterogeneity was accommodated by designing multiple primer sequences that were combined into an upstream pool of 5 oligonucleotides (PGMY11) and a downstream pool of 13 oligonucleotides (PGMY09), thereby avoiding use of degenerate bases that yield irreproducible primer syntheses. The performance of the PGMY09-PGMY11 (PGMY09/11) primer system relative to that of the standard MY09/11 system was evaluated with a set of 262 cervicovaginal lavage specimens. There was a 91.5% overall agreement between the two systems (kappa = 0.83; P < 0.001). The PGMY09/11 system appeared to be significantly more sensitive than the MY09/11 system, detecting an additional 20 HPV-positive specimens, for a prevalence of 62.8% versus a prevalence of 55.1% with the MY09/11 system (McNemar's ?2 = 17.2; P < 0.001). The proportion of multiple infections detected increased with the PGMY09/11 system (40.0 versus 33.8% of positive infections). HPV types 26, 35, 42, 45, 52, 54, 55, 59, 66, 73, and MM7 were detected at least 25% more often with the PGMY09/11 system. The PGMY09/11 primer system affords an increase in type-specific amplification sensitivity over that of the standard MY09/11 primer system. This new primer system will be useful in assessing the natural history of HPV infections, particularly when the analysis requires HPV typing.
Gravitt, P. E.; Peyton, C. L.; Alessi, T. Q.; Wheeler, C. M.; Coutlee, F.; Hildesheim, A.; Schiffman, M. H.; Scott, D. R.; Apple, R. J.
High-risk human papillomavirus (HR-HPV) genotype viral load and E6/E7 mRNA detection are proposed as surrogate markers of malignant cervical lesion progression. Currently, the use of commercially available DNA-based or mRNA-based tests is under investigation. In this study, the viral DNA load and E6/E7 mRNA detection of the five most common HR-HPV types detected in cervical cancer worldwide were compared in 308 cervical samples by using in-house type-specific quantitative real-time PCR assays and PreTect HPV-Proofer test, respectively. Sensitivity and negative predictive values were higher for the HPV-DNA assays combined (95.0% and 96.0%, respectively) than the RNA assays (77.0% and 88.0%, respectively); conversely, the mRNA test showed a higher specificity and higher positive predictive value (81.7% and 66.9%, respectively) than the DNA test (58.6% and 52.5%, respectively) for detecting histology-confirmed high-grade cervical intraepithelial neoplasia. A significantly higher association between viral DNA load and severity of disease was observed for HPV 16 and 31 (? = 0.62 and ? = 0.40, respectively) than for the other HPV types screened. A good degree of association between the two assays was found for detection of HPV 16 (k = 0.83), HPV 18 (k = 0.72), HPV 33 (k = 0.66), and HPV 45 (k = 0.60) but not for HPV 31 (k = 0.24). Sequence analysis in L1 and E6-LCR regions of HPV 31 genotypes showed a high level of intra-type variation. HR-HPV viral DNA load was significantly higher in E6/E7 mRNA positive than negative samples (P < 0.001), except for HPV 31. These findings suggest that transcriptional and replicative activities can coexist within the same sample. PMID:23280876
Broccolo, Francesco; Fusetti, Lisa; Rosini, Sandra; Caraceni, Donatella; Zappacosta, Roberta; Ciccocioppo, Lucia; Matteoli, Barbara; Halfon, Philippe; Malnati, Mauro S; Ceccherini-Nelli, Luca
The aim of this study was to devise a simple and reliable method for simultaneous detection and typing of genital human papillomaviruses (HPVs). The method comprises three steps (i) amplification of sample DNA with the L1 consensus primers, (ii) digestion of PCR products with restriction endonuclease RsaI and (iii) hybridization of digested PCR products with a unique oligonucleotide probe that detects different fragments of the six most common genital HPV genotypes, namely, HPV types 6, 11, 16, 18, 31 and 33. Seventeen clinical specimens were analyzed by this method and compared to Southern blot using full genomic HPV DNA probes and to PCR using type-specific probes. All three tests agreed with at least one HPV type; however, the new method identified more additional HPV types in cases of mixed infections. PMID:7946296
Chen, S; Tabrizi, S N; Fairley, C K; Borg, A J; Garland, S M
Background.?We have previously described the presentation of epidermodysplasia verruciformis (EV)–like eruptions in almost a quarter of hospitalized adolescents with vertically-acquired human immunodeficiency virus (HIV) infection in Harare, Zimbabwe, a region with a high prevalence of HIV infection. Methods.?We performed a clinical case note review and skin biopsy from affected sites in 4 HIV-infected adolescents with EV-like lesions in Harare. Biopsies were processed for histology and for human papillomavirus (HPV) typing. Results.?All patients had long-standing skin lesions that pre-dated the diagnosis of HIV by several years. The histology of skin biopsies from all patients was consistent with EV. In each biopsy, EV-associated ?-HPV type 5 was identified (additionally, type 19 was found in 1 biopsy). Cutaneous wart–associated HPV types 1 and 2 were detected in all biopsies, together with genital lesion–associated HPV types 6, 16, and 52, (as well as ?3 other genital lesion–associated HPV types). Despite immune reconstitution with combination antiretroviral therapy (cART), there was no improvement in EV-like lesions in any patient. Conclusions.?EV is a disfiguring and potentially stigmatizing condition among this patient group and is difficult to treat; cART appears to have no impact on the progression of skin disease. Among adolescents with longstanding HIV-induced immunosuppression and with high levels of sun exposure, close dermatological surveillance for potential skin malignancy is required.
Lowe, S. M.; Katsidzira, L.; Meys, R.; Sterling, J. C.; de Koning, M.; Quint, W.; Nathoo, K.; Munyati, S.; Ndhlovu, C. E.; Salisbury, J. R.; Bunker, C. B.; Corbett, E. L.; Miller, R. F.; Ferrand, R. A.
Human papillomavirus (HPVs) infect the genital epithelium and are found in proliferative lesions ranging from benign condylomata to invasive carcinomas. The immunological response to these infections is poorly understood because of the lack of purified viral antigens. In this study, bacterially derived fusion proteins expressing segments of all the major open reading frames (ORFs) of HPV type 6b (HPV-6b) have been used in Western blot (immunoblot) assays to detect antibodies directed against HPV-encoded proteins. The most striking reactivities present in sera from patients with genital warts were to the HPV-6b L1 ORF protein and, to a lesser extent, to the HPV-6b L2 ORF protein. Two cases of reactivity to HPV-6b E2 ORF were observed, but no reactivities were seen with other HPV-6b constructs. Two sera reacted with the HPV-16 L2 fusion protein, and two sera reacted with the HPV-16 E4 protein. The antibodies directed against the HPV-6b fusion proteins showed no cross-reactivity with comparable regions of the HPV-16 ORFs. This assay provides a useful approach for further studies of HPV serology. Images
Jenison, S A; Firzlaff, J M; Langenberg, A; Galloway, D A
While human papillomavirus (HPV) infection is associated with genital warts, anal cancer, and oral cancer, limited research has examined what men think causes these diseases. We sought to examine knowledge and beliefs about HPV-related disease among gay and bisexual men, who are at high risk for HPV infection and HPV-related cancers, and compare them to heterosexual men. We conducted an online survey in January 2009 with a national sample of men aged 18–59 who self-identified as either gay or bisexual (n = 312) or heterosexual (n = 296). The response rate was 70%. Fewer than half of men knew that HPV can cause genital warts (41%), anal cancer (24%), and oral cancers (23%). However, gay and bisexual men typically knew more than heterosexual men about these topics. Overall, most men believed that sexual behavior causes genital warts (70%) and anal cancer (54%), and tobacco use causes oral cancer (89%). Perceived causal factors differed substantially among the three diseases, while differences by sexual orientation were fewer and smaller in magnitude. Many men were unaware that HPV infection can cause genital warts, oral cancer, and anal cancer.
Ng, Terence W.; McRee, Annie-Laurie; Reiter, Paul L.
Human papillomaviruses (HPV) cause most cases of cervical cancer and large proportions of vaginal, vulvar, anal, penile, and oropharyngeal cancers. HPV also causes genital warts and recurrent respiratory papillomatosis. HPV vaccines could dramatically reduce the incidence of HPV-associated cancers and other conditions among both females and males, but uptake of the vaccines has fallen short of target levels. The President's Cancer Panel finds underuse of HPV vaccines a serious but correctable threat to progress against cancer.
Background To evaluate the pattern of co-infection of human papillomavirus (HPV) types in both sexes in Sweden. Methods Cell samples from genital swabs, first-void urine, and genital swabs immersed in first-void urine were collected in the present cross-sectional High Throughput HPV Monitoring study. Overall, 31,717 samples from women and 9,949 from men (mean age 25) were tested for 16 HPV types using mass spectrometry. Multilevel logistic regression was used to estimate the expected number of multiple infections with specific HPV types, adjusted for age, type of sample, and accounting for correlations between HPV types due to unobserved risk factors using sample-level random effects. Bonferroni correction was used to allow for multiple comparisons (120). Results Observed-to-expected ratio for any multiple infections was slightly above unity in both sexes, but, for most 2-type combinations, there was no evidence of significant departure from expected numbers. HPV6/18 was found more often and HPV51/68 and 6/68 less often than expected. However, HPV68 tended to be generally underrepresented in co-infections, suggesting a sub-optimal performance of our testing method for this HPV type. Conclusions We found no evidence for positive or negative clustering between HPV types included in the current prophylactic vaccines and other untargeted oncogenic types, in either sex.
Vaccarella, Salvatore; Soderlund-Strand, Anna; Franceschi, Silvia; Plummer, Martyn; Dillner, Joakim
The prevalence of genital human papillomavirus (HPV) infection was evaluated in 30 consecutive human immunodeficiency virus (HIV) + women by polymerase chain reaction (PCR)-in situ hybridization (ISH) on paraffin-embedded tissue sections and compared with that found with standard ISH. Biopsies were removed from normal or neoplastic areas in the cervix, vagina, and vulva, and ISH was performed with biotinylated or fluorescein isothiocyanate genomic DNA probes. One probe was used for HPV screening and others for HPV typing (types 6, 11, 16, 18, 31, and 33). Sequences were amplified by the "hot-start" PCR method and followed by standard ISH. Among the 30 HIV + women, 90% scored HPV + in one or several locations by PCR-ISH, whereas only 67% were positive by ISH. Oncogenic HPV types were found in 63% by PCR-ISH and in only 43% by ISH. The same HPV types detected by standard ISH were also recognized by PCR-ISH, but with the latter the signal was amplified. Moreover, some HPV types were found with PCR-ISH but not by ISH. We conclude that PCR-ISH is a valuable and sensitive method for specific detection of HPV. PMID:8727101
Walker, F; Bedel, C; Dauge-Geffroy, M C; Lehy, T; Madelenat, P; Potet, F
The human papillomavirus (HPV) minor capsid protein, L2, is a good candidate for prophylactic vaccine development because L2-specific antibodies have cross-neutralizing activity against diverse HPV types. Here, we developed a HPV mucosal vaccine candidate using the poly-?-glutamic acid synthetase A (pgsA) protein to display a partial HPV-16 L2 protein (N-terminal 1-224 amino acid) on the surface of Lactobacillus casei (L. casei). The oral immunization with L. casei-L2 induced productions of L2-specific serum IgG and vaginal IgG and IgA in Balb/c mice. To examine cross-neutralizing activity, we used a sensitive high-throughput neutralization assay based on HPV-16, -18, -45, -58, and bovine papillomavirus 1 (BPV1) pseudovirions. Our results revealed that mice vaccinated with L. casei-L2 not only generated neutralizing antibodies against HPV-16, but they also produced antibodies capable of cross-neutralizing the HPV-18, -45, and -58 pseudovirions. Consistent with previous reports, vaccination with HPV-16 L1 virus-like particles (VLPs) failed to show cross-neutralizing activity. Finally, we found that oral administration of L. casei-L2 induced significant neutralizing activities against genital infection by HPV-16, -18, -45, and -58 pseudovirions encoding a fluorescence reporter gene. These results collectively indicate that oral administration of L2 displayed on L. casei induces systemic and mucosal cross-neutralizing effects in mice. PMID:22426329
Yoon, Sun-Woo; Lee, Tae-Young; Kim, Sung-Jin; Lee, Il-Han; Sung, Moon-Hee; Park, Jong-Sup; Poo, Haryoung
Genital human papillomavirus (HPV) infections are among the most common sexually transmitted diseases. HPV is associated with a spectrum of diseases ranging from benign vulgar verrucae and condylomata accuminata to malignant cancers of the cervix, vulva, anus and penis. Genital HPV is in most cases transmitted sexually, but non-sexual routes of transmission, such as perinatal and autoinoculation, are possible. Men can be a reservoir of the virus that lives in latent or subclinical form on genital mucosa. Such an asymptomatic infection may be an oncogenic factor in the development of cervical cancer Colposcopic examination of the genitalia after the application of 3-5% acetic acid is a reliable method for the identification of subclinical HPV infection. Successful therapy of anogenital warts is characterized by their complete clearance, as well as by the lack of recurrence. Current treatments do not reliably eradicate HPV infections. The diagnosis and therapy of HPV infection in men is potentially beneficial because the eradication of penile HPV infection may decrease the reservoir of the virus. PMID:18982779
Ljubojevi?, Suzana; Lipozenci?, Jasna; Grgec, Dragana-Ljubojevi?; Prstaci?, Ratko; Skerlev, Michael; Mokos, Zrinka Bukvi?
While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4+ T cells. Also among women with genital tract Chlamydia infection, peripheral CD3+ CD4+ and CD3+ CD4- cells that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-?, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures.
Vicetti Miguel, Rodolfo D.; Harvey, Stephen A. K.; LaFramboise, William A.; Reighard, Seth D.; Matthews, Dean B.; Cherpes, Thomas L.
Human Papillomavirus (HPV) is a major cause of cervical cancer, precancerous lesions, cancer and other disease. HPV is the most common sexually transmitted infection. Although HPV virus primarily affects woman but it can also affects man because it cause of cancer of the anus, vulva, vagina, penis and some other cancers. HPV vaccines now used to prevent cervical cancer and genital warts because the vaccine protect against four types of HPV that most commonly cause disease are types 6, 11, 16, and 18. This paper is sequel work of Elbasha (2008). Difference with Elbasha (2008) are give alternative proof global stability, numerical simulation and interpretation. Global stability of the equilibrium on the model of a two-sex HPV vaccination were explored by using Lyapunov. Although we use the same lyapunov function, we use the largest invariant set to proof the global stability. The result show that the global stability of the equilibrium depends on the effective reproduction number (R). If R < 1 then the infection-free equilibrium is asymptotically stable globally. If R > 1 then endemic equilibrium have globally asymptotically stable properties. Then equilibrium proceed with the interpretation of numerical simulation.
Suryani, I.; Adi-Kusumo, F.
Summary Background VIN usual type appears to be related to the HPV’s oncogenic types. The aim of this prospective multicenter study was to evaluate the re-infection rate of high-risk HPV and the recurrence rate of VIN usual type after surgical treatment. Material/Methods The study enrolled 103 women affected by VIN usual type. They underwent wide local excision by CO2 laser. The patients were investigated by clinical evaluation and HPV DNA test 6 months after surgical treatment, and then were followed-up at 12, 18, 24, and 36 months. The recurrences were treated with re-excision. Results The rate of HPV infection after surgical treatment was 34% at 6 months, 36.9% at 12 months, 40% at 18 months, 41.7% at 24 months and 44.7% at 36 months. The mean time from HPV infection to the development of VIN was 18.8 months. Conclusions HPV testing in the follow-up of VIN usual type patients might be useful for identifying those patients with a higher risk of recurrence after surgical treatment, although more studies are needed. These preliminary data suggest that the test, in addition to clinical examination, can improve the efficacy of the follow-up.
Frega, Antonio; Sopracordevole, Francesco; Scirpa, Paolo; Biamonti, Alberto; Lorenzon, Laura; Scarani, Simona; De Sanctis, Luana; Pacchiarotti, Arianna; Moscarini, Massimo; French, Deborah
Background Human papillomavirus (HPV) is the aetiological agent for cervical cancer and genital warts. Concurrent HPV and HIV infection in the South African population is high. HIV positive (+) women are often infected with multiple, rare and undetermined HPV types. Data on HPV incidence and genotype distribution are based on commercial HPV detection kits, but these kits may not detect all HPV types in HIV?+?women. The objectives of this study were to (i) identify the HPV types not detected by commercial genotyping kits present in a cervical specimen from an HIV positive South African woman using next generation sequencing, and (ii) determine if these types were prevalent in a cohort of HIV-infected South African women. Methods Total DNA was isolated from 109 cervical specimens from South African HIV?+?women. A specimen within this cohort representing a complex multiple HPV infection, with 12 HPV genotypes detected by the Roche Linear Array HPV genotyping (LA) kit, was selected for next generation sequencing analysis. All HPV types present in this cervical specimen were identified by Illumina sequencing of the extracted DNA following rolling circle amplification. The prevalence of the HPV types identified by sequencing, but not included in the Roche LA, was then determined in the 109 HIV positive South African women by type-specific PCR. Results Illumina sequencing identified a total of 16 HPV genotypes in the selected specimen, with four genotypes (HPV-30, 74, 86 and 90) not included in the commercial kit. The prevalence’s of HPV-30, 74, 86 and 90 in 109 HIV positive South African women were found to be 14.6%, 12.8%, 4.6% and 8.3% respectively. Conclusions Our results indicate that there are HPV types, with substantial prevalence, in HIV positive women not being detected in molecular epidemiology studies using commercial kits. The significance of these types in relation to cervical disease remains to be investigated.
Human papillomavirus (HPV) is the etiologic agent of genital warts. Genital warts are transmitted through sexual contacts and caused in about 90% of the cases by HPV types 6 and 11. Worldwide, several million cases of genital warts occur each year both in females and males. In Italy, genital warts are not subject to mandatory notification; the only available data come from the sentinel surveillance system for sexually transmitted infections (STI), which show that external genital warts represent the most frequent STI in Italy. However, these data are not suitable for estimates of incidence and prevalence of single STI in the general population. To obtain more reliable data on the epidemiology of genital warts in the female population at large, we implemented a network of local gynecologists reporting essential data on all women visited throughout one year and detailed data on women who were diagnosed with genital warts. In order to organize and create this network, a partnership between the Italian National Institute of Health and the Italian Society of Gynecology and Obstetrics was constituted to implement the start-up and management of this pilot and unique project in Europe. The present paper intends to present the methods used to build and implement this surveillance network of local gynecologists. PMID:24096294
Suligoi, B; Salfa, M C; Mariani, L; Corsini, D; Timelli, L; Fattorini, G; Vittori, G
Background Endocavity ultrasound is seen as a harmless procedure and has become a common gynaecological procedure. However without correct disinfection, it may result in nosocomial transmission of genito-urinary pathogens, such as high-risk Human Papillomavirus (HR-HPV). We aimed to evaluate the currently recommended disinfection procedure for covered endocavity ultrasound probes, which consists of “Low Level Disinfection” (LLD) with “quaternary ammonium compounds” containing wipes. Methods From May to October 2011 swabs were taken from endovaginal ultrasound probes at the Gynecology Department of the Lyon University Hospital. During the first phase (May–June 2011) samples were taken after the ultrasound examination and after the LLD procedure. In a second phase (July–October 2011) swab samples were collected just before the probe was used. All samples were tested for the presence of human DNA (as a marker for a possible transmission of infectious pathogens from the genital tract) and HPV DNA with the Genomica DNA microarray (35 different HPV genotypes). Results We collected 217 samples before and 200 samples after the ultrasound examination. The PCR was inhibited in two cases. Human DNA was detected in 36 (18%) post-examination samples and 61 (28%) pre-examination samples. After the ultrasound LLD procedure, 6 (3.0%) samples contained HR-HPV types (16, 31, 2×53 and 58). Similarly, HPV was detected in 6 pre-examination samples (2.7%). Amongst these 4 (1.9%) contained HR-HPV (types 53 and 70). Conclusion Our study reveals that a considerable number of ultrasound probes are contaminated with human and HR-HPV DNA, despite LLD disinfection and probe cover. In all hospitals, where LLD is performed, the endovaginal ultrasound procedure must therefore be considered a source for nosocomial HR-HPV infections. We recommend the stringent use of high-level disinfectants, such as glutaraldehyde or hydrogen peroxide solutions.
Casalegno, Jean-sebastien; Le Bail Carval, Karine; Eibach, Daniel; Valdeyron, Marie-Laure; Lamblin, Gery; Jacquemoud, Herve; Mellier, Georges; Lina, Bruno; Gaucherand, Pascal; Mathevet, Patrice; Mekki, Yahia
Specific human papillomavirus (HPV) types have been implicated in the development of cervical carcinoma worldwide. Novel molecular techniques have facilitated the detection and typing of HPV in cervical lesions. DNA preparations from a series of 23 histopathologically confirmed cervical carcinoma patients were analyzed by polymerase chain reaction (PCR) using degenerate primers for the presence of HPV DNA sequences. A total of 22 of 23 cases studied (95.7%) were found positive for HPV DNA sequences. Further studies by DNA hybridization with viral specific probe and restriction enzyme analysis demonstrated the presence of HPV 16 in 73.9% (17/23) and HPV 18 in 65.2% (15/23) of the cases examined. Interestingly, the uncommon HPV 31 and 33 were also found but with a lower percentage (16.9%). It was noted that HPV 16 frequency in the carcinoma increased with age but HPV 18 was evenly present at all ages investigated. We found that HPV was frequently associated with the majority of the cervical carcinomas, and in all but one case, oncogenic high risk HPV genotypes were present. We conclude that HPV infection of the genital tract has an important role in the development of the disease in Malaysia. PMID:7752979
Yadav, M; Nurhayati, Z A; Padmanathan, A; Abdul Aziz, Y; Norhanom, A W
Because of the major clinical impact of bronchial cancer worldwide, the possibility that human papillomavirus (HPV) contributes to its pathogenesis as a co-carcinogen is an intriguing one. Bronchial squamous cell carcinoma develops through well defined precursor lesions, often at the sites of squamous metaplasia. Benign squamous cell papillomas are rare but HPV DNA has been found in almost half of those studied, implicating a causal association. In invasive bronchial cancer, morphological changes seen in HPV lesions elsewhere are often seen. HPV DNA has been detected in 21.7% of the 2468 bronchial carcinomas analysed to date and the same high risk types implicated in other squamous cell cancers have been identified. Clearly, more effort should be focused on assessing the role of HPV in bronchial carcinogenesis, by analysing the synergistic effects of carcinogenic agents (cigarette smoke, radiation, asbestos, etc) and HPV in different experimental settings.
Syrjanen, K J
BACKGROUND: Genital warts, which are caused by infection with human papillomavirus (HPV), are one of the most common sexually transmitted diseases in Europe. Although genital warts are commonly perceived as a non-serious condition, treatment is often long, of varying effectiveness and the recurrence rate is high. Very few studies have been performed on the personal consequences of genital warts. The
Gitte Lee Mortensen; Helle K Larsen
The recent policy statement by the Cancer Council of Australia on infant circumcision and cancer prevention and the announcement that the quadrivalent human papillomavirus (HPV) vaccine will be made available for boys in Australia prompted us to provide an assessment of genital cancer prevention. While HPV vaccination of boys should help reduce anal cancer in homosexual men and cervical cancer in women, it will have little or no impact on penile or prostate cancer. Male circumcision can reduce cervical, penile and possibly prostate cancer. Promotion of both HPV vaccination and male circumcision will synergistically maximize genital cancer prevention.
Morris, Brian J; Mindel, Adrian; Tobian, Aaron AR; Hankins, Catherine A; Gray, Ronald H; Bailey, Robert C; Bosch, Xavier; Wodak, Alex D
The historical developments in the recognition of the role of human papillomavirus (HPV) infection in cells and tissues of the female genital tract are briefly summarized. The identification of a specific marker cell, the koilocyte, has led to initial studies of frequency and biologic significance of neoplastic lesions of the uterine cervix associated with HPV. By molecular virology techniques, over 40 types of HPV have been identified and their tissue affinity determined. Types 6, 11, 16, 18, and 31 are most commonly associated with anogenital lesions, among them a broad spectrum of cervical intraepithelial neoplasia (CIN). While current evidence suggests that lesions associated with HPV Types 6 and 11 are potentially less harmful to the patient than lesions associated with HPV Types 16 and 18 (which have been identified also in invasive cervical carcinomas and cell lines derived therefrom), a major long term prospective study may be required to confirm this view. A factor that complicates the issue still further is the recent observation that HPV DNA of all four types has been identified in 11% of women and 5.5% of men free of disease. Infection with multiple viral types (including Types 16 and 18) was common in this apparently healthy population. Although HPV must be considered as a prime candidate for a transforming virus, current evidence suggests that the infection with the virus is per se an insufficient condition for the development of precancerous lesions or cancer of the uterine cervix and that another factor or factors may be necessary for these events to take place. Some of these possible cofactors such as age, repeated infections, and the immune status of the patient are discussed. A great deal of additional work is required before the precise role of HPV virus in the genesis of carcinoma of the uterine cervix, vulva, and vagina is firmly documented. PMID:2820565
Koss, L G
The human papillomavirus (HPV) represents a significant public health burden because of its widespread prevalence, its links to genital warts and cancers, and the negative psychosocial impact of HPV infection and diagnosis. Scholars have attributed some of these negative effects to insufficient knowledge and information about HPV, prompting research on women's HPV information preferences; however, little is known about how women obtain, avoid, and use this information. To address this lacuna, we designed a study to trace the information management processes of women with HPV. Our analysis of interviews with 25 women living with HPV revealed a common sequence of emotional, cognitive, and behavioral responses to the HPV diagnosis. The authors review these findings and articulate their relevance and importance to research, theory, and practice in the discussion. PMID:24580554
Kosenko, Kami A; Harvey-Knowles, Jacquelyn; Hurley, Ryan J
Background Infection with human papillomavirus (HPV) 16 or HPV18 elicits an antibody response, but whether the elicited antibodies protect women against subsequent infection by a homologous HPV type compared with seronegative women is unknown. Methods Study participants were women aged 18–25 years at enrollment in the control group of the ongoing National Cancer Institute–sponsored, community-based, randomized HPV16/18 Costa Rica Vaccine Trial. At enrollment, 2813 participants were negative for cervical HPV16 DNA and 2950 for HPV18 DNA. Women were interviewed regarding sociodemographic data and medical and health history. Medical and pelvic examinations were conducted for all consenting sexually experienced women. Serum samples taken at enrollment were tested for total HPV16/18 antibodies with a polyclonal enzyme-linked immunosorbent assay, and cervical specimens were tested for type-specific HPV DNA over 4 years of follow-up. Using Poisson regression, we compared rate ratios of newly detected cervical HPV16 or HPV18 infection among homologous HPV-seropositive and HPV-seronegative women, adjusting for age, education, marital status, lifetime number of sexual partners, and smoking. Results There were 231 newly detected HPV16 infections during 5886 person-years among HPV16-seronegative women compared with 12 newly detected HPV16 infections during 581 person-years among HPV16-seropositive women with the highest HPV16 sero-levels. There were 136 newly detected HPV18 infections during 6352 person-years among HPV18-seronegative women compared with six new infections detected during 675 person-years among HPV18 seropositives with the highest sero-levels. After controlling for risk factors associated with newly detected HPV infection, having high HPV16 antibody titer at enrollment was associated with a reduced risk of subsequent HPV16 infection (women in the highest tertile of HPV16 antibody titers, adjusted rate ratio = 0.50, 95% confidence interval = 0.26 to 0.86 vs HPV16-seronegative women). Similarly, having high HPV18 antibody titer at enrollment was associated with a reduced risk of subsequent HPV18 infection (women in the highest tertile of HPV18 antibody titers, adjusted rate ratio = 0.36, 95% confidence interval = 0.14 to 0.76 vs HPV18-seronegative women). Conclusion In this study population, having high antibody levels against HPV16 and HPV18 following natural infection was associated with reduced risk of subsequent HPV16 and HPV18 infections.
Porras, Carolina; Schiffman, Mark; Rodriguez, Ana Cecilia; Wacholder, Sholom; Gonzalez, Paula; Quint, Wim; van Doorn, Leen-Jan; Sherman, Mark E.; Xhenseval, Valerie; Herrero, Rolando; Hildesheim, Allan
Measuring HPV exposure relies on detection of HPV type-specific antibodies, but methods are not standardized. Additionally, there is little information on the best sample type for HPV antibody detection. This study validated pseudovirion neutralization (PVN) assay for HPV antibody detection and compared it to IgG ELISA. Both assays were applied to paired serum and cervical mucus samples. Additionally, PVN assay
Emily L. Blalock
A randomized double-blind placebo-controlled phase II trial was conducted to evaluate the efficacy of a prophylactic quadrivalent vaccine targeting the human papillomavirus (HPV) types most frequently associated with cervical cancer (types 16/18) and genital warts (types 6/11) in Japanese women aged 18-26 years. Participants were randomly assigned to either quadrivalent HPV (types 6/11/16/18) L1 virus-like particle vaccine (GARDASIL) (n = 509) or placebo (n = 512). Participants underwent regular gynecological examinations, cervicovaginal sampling for HPV DNA, testing for serum neutralizing antibodies to HPV and Papanicolau testing. The primary end-point was the combined incidence of persistent infection with HPV types 6, 11, 16 or 18 and cervical or external genital disease (i.e. cervical intraepithelial neoplasia, cervical cancer or external genital lesions related to HPV 6, 11, 16 or 18. Primary analyses were done per protocol. Combined incidence of persistent infection or disease with HPV 6, 11, 16 or 18 fell by 87.6% (95% confidence interval [CI], 59.2-97.6; P < 0.001), with HPV 6 or 11 by 73.1% (95% CI, -1.1-97.3; P = 0.0756) and with HPV 16 or 18 by 94.5% (95% CI, 65.2-99.9; P < 0.001) in those assigned vaccine compared with those assigned placebo. The median duration of follow up after month 7 in subjects was 23 months. In addition, the vaccine was well tolerated in Japanese women aged 18-26 years. Quadrivalent HPV vaccine could significantly reduce the acquisition of infection and clinical disease caused by HPV types 6, 11, 16 and 18. PMID:23331518
Yoshikawa, Hiroyuki; Ebihara, Keiko; Tanaka, Yoshiyuki; Noda, Kiichiro
Human papillomaviruses (HPV) are the most frequently sexually transmitted viruses and etiological agents of several human cancers. Controversial results of the role of HPV in infertile population on sperm parameters have been published. The aim of this study was to estimate the type-specific prevalence of HPV DNA infection of the external genitalia and semen in 340 Slovenian men from infertile couples and to establish the relationship between seminal HPV DNA infection and abnormal sperm parameters. Self-taken swabs of the entire penile surface and semen samples were collected, and HPV detection and genotyping were performed. HPV DNA was detected in 37.12% of external genitalia and in 13.61% of semen samples with high HPV type concordance of both sampling sites. The most prevalent HPV types in the male external genitalia were HPV-CP6108 and HPV-84. The most prevalent HPV types in semen were HPV-53 and HPV-CP6108. The prevalence of HPV infection between normozoospermic men and men with abnormal sperm parameters did not differ significantly. Sperm quality did not differ significantly between men with seminal HPV infection and uninfected men. In conclusion, the men from infertile couples are equally susceptible to HPV infection regardless of their fertile potential; seminal HPV infection does not impair sperm quality.
Golob, Barbara; Verdenik, Ivan; Kolbezen Simoniti, Mojca; Vrtacnik Bokal, Eda; Zorn, Branko
Abstract Multidrug-resistant (MDR) HIV-1 presents a challenge to the efficacy of antiretroviral therapy (ART). To examine mechanisms leading to MDR variants in infected individuals, we studied recombination between single viral genomes from the genital tract and plasma of a woman initiating ART. We determined HIV-1 RNA sequences and drug resistance profiles of 159 unique viral variants obtained before ART and semiannually for 4 years thereafter. Soon after initiating zidovudine, lamivudine, and nevirapine, resistant variants and intrapatient HIV-1 recombinants were detected in both compartments; the recombinants had inherited genetic material from both genital and plasma-derived viruses. Twenty-three unique recombinants were documented during 4 years of therapy, comprising ?22% of variants. Most recombinant genomes displayed similar breakpoints and clustered phylogenetically, suggesting evolution from common ancestors. Longitudinal analysis demonstrated that MDR recombinants were common and persistent, demonstrating that recombination, in addition to point mutation, can contribute to the evolution of MDR HIV-1 in viremic individuals.
Kemal, Kimdar S.; Ramirez, Christina M.; Burger, Harold; Foley, Brian; Mayers, Douglas; Klimkait, Thomas; Hamy, Francois; Anastos, Kathryn; Petrovic, Katarina; Minin, Vladimir N.; Suchard, Marc A.
Multidrug-resistant (MDR) HIV-1 presents a challenge to the efficacy of antiretroviral therapy (ART). To examine mechanisms leading to MDR variants in infected individuals, we studied recombination between single viral genomes from the genital tract and plasma of a woman initiating ART. We determined HIV-1 RNA sequences and drug resistance profiles of 159 unique viral variants obtained before ART and semiannually for 4 years thereafter. Soon after initiating zidovudine, lamivudine, and nevirapine, resistant variants and intrapatient HIV-1 recombinants were detected in both compartments; the recombinants had inherited genetic material from both genital and plasma-derived viruses. Twenty-three unique recombinants were documented during 4 years of therapy, comprising ~22% of variants. Most recombinant genomes displayed similar breakpoints and clustered phylogenetically, suggesting evolution from common ancestors. Longitudinal analysis demonstrated that MDR recombinants were common and persistent, demonstrating that recombination, in addition to point mutation, can contribute to the evolution of MDR HIV-1 in viremic individuals. PMID:22364185
Kemal, Kimdar S; Ramirez, Christina M; Burger, Harold; Foley, Brian; Mayers, Douglas; Klimkait, Thomas; Hamy, François; Anastos, Kathryn; Petrovic, Katarina; Minin, Vladimir N; Suchard, Marc A; Weiser, Barbara
Ten patients with biliary-type pain, in whom investigations of the biliary tract were negative, are reported. All the patients were sexually active premenopausal women and all had evidence of infection with chlamydia trachomatis. Five patients submitted to laparoscopy had fibrinous adhesions between the anterior surface of the liver and the parietal peritoneum (perihepatitis). All 10 patients were diagnosed as suffering from the Curtis-Fitz-Hugh syndrome caused by Chlamydia trachomatis. The clinical similarities between the Curtis-Fitz-Hugh syndrome (right upper quadrant abdominal pain, perihepatitis and genital tract infection) and acute biliary disease are emphasized and the diagnostic implications discussed. PMID:7074334
Wood, J J; Bolton, J P; Cannon, S R; Allan, A; O'Connor, B H; Darougar, S
We have shown that the spermicidal agent benzalkonium chloride can exert a direct inhibitory effect on the viral reverse transcriptase activity of human immunodeficiency virus type 1 (HIV-1) when utilized at concentrations of 0.05% and higher. Exposure of HIV-1 to this disinfectant at concentrations of more than 0.05% was able to completely destroy viral infectivity, as assessed on susceptible target cells. We have further shown that HIV-1, which is present in both seminal and genital secretions, can be inactivated in such fluids by direct exposure to benzalkonium chloride.
Wainberg, M A; Spira, B; Bleau, G; Thomas, R
Attenuated strains of Salmonella are attractive live vaccine candidates for eliciting mucosal as well as systemic immune responses. The ability to induce immune responses in the reproductive tract may be critical for the effectiveness of a prophylactic vaccine against genital human papillomaviruses (HPV), which are important etiologic agents in the development of cervical cancer. To examine the potential of a live Salmonella-based vaccine to prevent genital HPV infection, the L1 major capsid protein from HPV type 16 (HPV16) was constitutively expressed in the PhoPc strain of Salmonella typhimurium. As demonstrated by electron microscopy, the L1 protein expressed in these bacteria assembled into virus-like particles (VLPs) that resemble authentic papillomavirus virions. This is the first demonstration that papillomavirus VLPs can self-assemble in prokaryotes. BALB/c mice were immunized with the HPV16 L1 recombinant PhoPc strain by the oral and nasal routes. Despite a low stability of the L1-expressing plasmid in vivo, a double nasal immunization was effective in inducing L1-specific serum antibodies that recognized mainly native, but not disassembled, VLPs. These antibodies effectively neutralized HPV16 pseudotyped virions in an in vitro infectivity assay. Conformationally dependent anti-VLP immunoglobulin A (IgA) and IgG were also detected in oral and vaginal secretions, indicating that potentially protective antibody responses were elicited at mucosal sites. Recombinant attenuated Salmonella expressing HPV capsids may represent a promising vaccine candidate against genital HPV infection.
Nardelli-Haefliger, D; Roden, R B; Benyacoub, J; Sahli, R; Kraehenbuhl, J P; Schiller, J T; Lachat, P; Potts, A; De Grandi, P
The four steps in the prevention of human papillomavirus-associated neoplasia: considerations for preventive measures, screening, disease impact, and potential overtreatments in HPV-related pathology.
There is no cure currently available for HPV infections, although ablative and excisional treatments of some dysplasias often result in a clinical and virological cure. Effective control measures of HPV-associated cancers rely on the prevention at four different levels. Apart from sexual abstinence, primary prevention is realized through vaccines targeting the most frequent HPV types: negative attitudes towards HPV vaccination and high costs are the main obstacles. The aim of secondary prevention is to detect precancerous changes before they develop into invasive cancer, while tertiary prevention involves actual treatment of high-grade lesions: in many countries routine screening with cytology is being challenged with HPV DNA testing. Quaternary prevention comprehends those actions adopted to mitigate or avoid unnecessary or excessive medical interventions, and may well be addressed in avoiding treatments for low-grade intraepithelial neoplasia. Though some gynecologists commonly recommend treatment for low-grade disease and women tend to prefer active management if not properly informed, harms arising from unnecessary treatments, increased costs, work overload for second-level health services, and induced psychosocial distress are causing on-going problems. Prevention efforts of genital HPV-associated cancers should concentrate in: (1) enhancing primary prevention through vaccination of all eligible subjects, (2) achieving high levels of adherence to routine screening programs, (3) treating precancerous lesions, and (4) monitoring current guidelines recommendations to avoid overtreatments. Novel research projects should be designed to study the delicate mechanisms of immune response to HPV. PMID:23974280
Liverani, Carlo A
The aim of the study was to assess the clinical efficiency of quadrivalent HPV (types 6/11/16/18) vaccine in patients with recurrent respiratory papillomatosis (RRP). This was a prospective study of patients with RRP treated from January 2009 to July 2012 at the Ear, Nose and Throat Department of the Emergency County Hospital of Cluj-Napoca, Romania. Demographic characteristics, onset of RRP, HPV typing, use and number of cidofovir injections, number of surgeries for RRP per year, and use of human papillomavirus vaccine (types 6, 11, 16, 18) (recombinant, adsorbed)/Silgard® were considered from all the patients included in the study. Charts were reviewed for follow-up after diagnosis, after cidofovir, and after Silgard; all the statistical tests were applied at a significance level of 5%. The recurrences were observed within 27.53 ± 11.24 days after intralesional cidofovir injection. Thirteen patients with recurrence after cidofovir agreed and received Silgard® vaccine. 85% [54.44–99.41] of patients had no recurrences during 1-year follow-up. The recurrence of papillomas was observed in two patients (15%, 95% CI [0.59–45.56]), one with adult-onset RRP and one with juvenile-onset RRP. Both recurrences appeared after the first Silgard dose; one month after the third vaccine dose each patient underwent a new surgery for remaining papillomas with no recurrences at 1-year follow-up visit. Silgard® vaccination had a good effect and proved to be efficient in the treatment of our patients with RRR without appearance of recurrence in 85% of the patients during 1-year follow-up. PMID:24121781
Chiril?, Magdalena; Bolboac?, Sorana D
Cervical screening programmes are moving towards HPV testing as part of the screening process and as a triage for colposcopy. Three HPV detection methods were evaluated using cervical cytology specimens from colposcopy patients. PreservCyt™ liquid based cytology specimens from 241 women attending colposcopy clinics with greater than 2 persistently abnormal smears were recruited through the Coombe Women and Infants University Hospital, Dublin. HPV DNA was detected by Hybrid Capture (HC2) for 13 high-risk HPV types, Full-Spectrum HPV (FS-HPV) for 49 high and low-risk types and Molecular Beacon Real-Time HPV assay (MBRT-HPV) for 16 high and low-risk types. HPV genotyping was performed using Linear Array HPV Assay (LA-HPV). HPV was detected in 83.3% (195/234), 91.9% (217/236) and 80.1% (169/211) of cytology specimens by HC2, FS-HPV and MBRT-HPV, HPV DNA detection assays. The sensitivity of the assays for the detection of high-risk HPV in cytology specimens that had a Cervical Intraepithelial Neoplasia Grade 2+ result by histology were, 98%, 97% and 94% for HC2, FS-HPV and MBRT-HPV assays with positive predictive values of 94.1%, 94.1% and 97.3%. The most common HPV genotypes were HPV 16, 31, 33, 58, 42, 61 and 53, and the most common high-risk HPV genotypes were HPV 16, 31, 33, 58, 18, 45, 59, 51, 56 and 39, with detection of multiple infections in 57.7% of all cases. FS-HPV and MBRT-HPV are highly sensitive and have a similarly high PPV as the HC2 assay for detection of HPV in patients with Cervical Intraepithelial Neoplasia Grade 2+ disease. HPV genotyping of women with persistent abnormalities is warranted prior to the introduction of HPV DNA testing in a colposcopy setting. PMID:24583109
Keegan, Helen; Pilkington, Loretto; McInerney, Jamie; Jeney, Csaba; Benczik, Márta; Cleary, Sinead; von Bunau, Gunther; Turner, Michael; D'Arcy, Tom; O' Toole, Sharon; Pal-Szenthe, Borbála; Kaltenecker, Borbàla; Mózes, Johanna; Kovács, Anette; Solt, Agnes; Bolger, Noel; O'Leary, John; Martin, Cara
Incidences of different types of cancer are increasing in Pakistan, among which cancer of Cervix and Respiratory pappilomatosis are of great concern because of their association with human Pappilomavirus (HPV). Cervical cancers typically distress women of middle age or older; however it may affect women in any age after the puberty. Two serotypes of HPV (16 & 18) accounts 70% of cervical cancer cases, while HPV (6 & 11) are considered low-risk viruses associated with genital warts (Condyloma acuminata) and Respiratory pappilomatosis in both gender. Generally, there is transient role of HPV in human body and are removed by immune system in or around 1 year. Data from different Pakistani hospitals provides sound evidence for increasing trends of cervical cancer, which is, being developing country imperative for us. As the cost of cancer management is increasing day by day with poor survival rate and its burden is borne by patient, their family or society in-large, so if screening or prevention is possible then there would be need to identify target population for screening and vaccination. By quality adjusted life year (QALY) measurement, the data from different sources indicates that adolescent age is the appropriate target population and is cost effective for vaccination. Two vaccines manufactured by recombinant DNA technology are licensed in some parts of the world for prevention of HPV related cancers, however both have certain advantage over another, as one of the vaccines contains viral like proteins of two HPV serotypes 16 & 18 and provide additional cross protection against HPV type 13 and 45 with 100% seroprotection, while the other vaccine, being quadrivalent offers protection against four serotypes 6, 11, 16 and 18. Both vaccines tolerability and safety profiles are similar and acceptable, however bivalent vaccine appears to provide long-lasting immunity by the development of memory B-cells hypothetically due to difference of adsorbing agent used by manufacturer, on the other hand, quadrivalent vaccine offers protection against cervical cancer but also offers additional protection against Condyloma acuminata and respiratory Pappilomatosis. As these vaccines are new in the market and initial trials indicate availability of antibodies for up to around 5 years i.e. why it is controversial at the moment that whether booster dose is recommended or not, however it is assumed that, there is no harm to have booster dose at 5th year of vaccination. PMID:23009992
Khaliq, Sheikh Abdul; Shyum Naqvi, Syed Baqir; Fatima, Anab
... trial of Cervarix in Costa Rica, where cervical cancer rates are high. This study is designed to obtain information about the vaccine's longer-term safety, the extent and duration of protection, the immune mechanisms of protection, and the natural history of infection with HPV types other than ...
Objective. To evaluate the prevalence of HSV-1 and HSV-2 in pregnant and nonpregnant women, testing the correlation between DNA of the viruses with colposcopic and/or cytological changes, and evaluate association with sociodemographic characteristics and sexual activity. Methods. Included in this study were 106 pregnant and 130 nonpregnant women treated at primary health care units of Natal, Brazil, in the period 2010-2011. The patients were examined by colposcopy, and two cervical specimens were collected: one for cytology examination and another for analysis by PCR for detection of HSV-1 and HSV-2. Results. HSV-1 alone was detected in 16.0% of pregnant and 30.0% of nonpregnant women. For HSV-2, these rates were 12.3% and 15.5%, respectively. HSV-2 had a higher correlation with cytology and/or colposcopy changes than HSV-1 did. Genital HSV-1 infection was not associated with any of the variables tested, whereas HSV-2 infection was associated with ethnicity, marital status, and number of sexual partners. Conclusions. The prevalence of HSV-1 was higher than that observed for HSV-2 in both pregnant and nonpregnant women. The genital infection by HSV-2 was higher in women with changed colposcopy and/or cytology, and it was associated with ethnicity, marital status, and number of sexual partners.
Miranda, Cleine Aglacy Nunes; Lima, Erika Galvao; de Lima, Diego Breno Soares; Cobucci, Ricardo Ney Oliveira; Cornetta, Maria da Conceicao de Mesquita; Fernandes, Thales Allyrio Araujo de Medeiros; de Azevedo, Paulo Roberto Medeiros; de Azevedo, Jenner Chrystian Verissimo; de Araujo, Joselio Maria Galvao; Fernandes, Jose Verissimo
Premalignant lesions of the lower female genital tract encompassing the cervix, vagina and vulva are variably common and many, but by no means all, are related to infection by human papillomavirus (HPV). In this review, pathological aspects of the various premalignant lesions are discussed, mainly concentrating on new developments. The value of ancillary studies, mainly immunohistochemical, is discussed at the appropriate points. In the cervix, the terminology and morphological features of premalignant glandular lesions is covered, as is the distinction between adenocarcinoma in situ (AIS) and early invasive adenocarcinoma, which may be very problematic. A spectrum of benign, premalignant and malignant cervical glandular lesions exhibiting gastric differentiation is emerging with lobular endocervical glandular hyperplasia (LEGH), including so-called atypical LEGH, representing a possible precursor of non HPV-related cervical adenocarcinomas exhibiting gastric differentiation; these include the cytologically bland adenoma malignum and the morphologically malignant gastric type adenocarcinoma. Stratified mucin producing intraepithelial lesion (SMILE) is a premalignant cervical lesion with morphological overlap between cervical intraepithelial neoplasia (CIN) and AIS and which is variably regarded as a form of reserve cell dysplasia or stratified AIS. It is now firmly established that there are two distinct types of vulval intraepithelial neoplasia (VIN) with a different pathogenesis, molecular events, morphological features and risk of progression to squamous carcinoma. These comprise a more common HPV-related usual type VIN (also referred to as classic, undifferentiated, basaloid, warty, Bowenoid type) and a more uncommon differentiated (simplex) type which is non-HPV related and which is sometimes associated with lichen sclerosus. The former has a relatively low risk of progression to HPV-related vulval squamous carcinoma and the latter a high risk of progression to non-HPV related vulval squamous carcinoma. Various aspects of vulval Paget's disease are also discussed. PMID:23442737
McCluggage, W Glenn
Background: This study was performed to compare the prevalence of HPV infection and high risk HPV genotypes [16, 18] between monogamous and polygamous women, in Zabol, Iran. Methods: This cross sectional study was conducted in Zabol in 2006 – 2007. Two hundred sixty five married women attending the Gynecology Clinic for Cervical Disease Screening entered to this study. One hundred sixty two cases had monogamous, and 103 had polygamous husbands. HPV PCR samples were obtained from scrape of papsmear specimens. The biotinylated primers MY09/MY11, GP5+/GP6+, were utilized to enable amplification and detection of positive PCR products. Confirmation of HPV-16 and -18 were done by type-specific PCR primers HPV-16/F, HPV-16/R and HPV-18/F, HPV-18/R. Results: Prevalence of HPV infection in monogamous and polygamous groups was 29% and 37.9%, respectively. The most HPV infection was found in 15–25 years group. The most prevalence of infection in monogamous group was HPV-18 and HPV-non16, 18 in 15–25 years, and HPV-16 in 26–35 years group. In polygamous group the most prevalent type was HPV-16, 18 in 15–25 years group. The most prevalent HPV-16 was seen in sever inflammation and dysplasia cytology in both groups. Conclusion: Prevalence of HPV infection in Zabol is high, and in women with polygamous husbands group is slightly more than monogamous. Screening for this infection must be recommended in this region of Iran.
Shahramian, I; Heidari, Z; Mahmoudzadeh-Sagheb, HR; Moradi, A; Forghani, F
Most human papillomavirus (HPV)-associated cervical intraepithelial neoplasia (CIN) lesions in normal women regress spontaneously, but a small number persist and may progress to invasive cancer. To evaluate the role of immunity to HPV and the outcome of CIN and associated HPV infection, we examined cell-mediated immune (CMI) responses to HPV 16 E6 and E7 peptides. One hundred thirty-six women with
Anna S. Kadish; Patrick Timmins; Yuexian Wang; Gloria Y. F. Ho; Robert D. Burk; John Ketz; Seymour L. Romney; Anne Johnson; Ruth Angeletti; Maria Abadi
Genital human papillomavirus (HPV) infection is the most common sexually transmitted virus in the United States, causing genital warts, cervical cell abnormalities, and cervical cancer in women. To inform HPV education efforts, 35 focus groups were conducted with members of the general public, stratified by gender, race/ethnicity, and urban/rural…
Friedman, Allison L.; Shepeard, Hilda
This report demonstrates that normal human fibroblasts can be immortalized by the introduction of HPV-16 E6-E7 genes. We designed zinc-inducible expression plasmids with HPV-16 E6, E7 or both. Each plasmid was introduced into normal human fibroblasts (TIG-3 cells) using lipofection methods. Only transfectants with the HPV-16 E6-E7 zinc-inducible expression plasmid, which were cultured in medium supplemented with 100 microM ZnSO4, overcame crisis and could be cultured over 200 population doubling levels (PDLs). These cell lines showed the reactivation of telomerase after crisis, and morphological alterations were also observed. PMID:9159405
Shiga, T; Shirasawa, H; Shimizu, K; Dezawa, M; Masuda, Y; Simizu, B
... Genital Herpes - CDC Fact Sheet Herpes is a common sexually transmitted disease (STD) that any sexually active person can get. ... to know that even without signs of the disease, it can still spread to sexual partners. Basic Fact Sheet | Detailed Version Español ... & Pregnancy Symptoms Diagnosis ...
The induction of persistent intraepithelial CD8+ T cell responses may be key to the development of vaccines against mucosally transmitted pathogens, particularly for sexually transmitted diseases. Here we investigated CD8+ T cell responses in the female mouse cervicovaginal mucosa after intravaginal immunization with human papillomavirus vectors (HPV pseudoviruses) that transiently expressed a model antigen, respiratory syncytial virus (RSV) M/M2, in cervicovaginal keratinocytes. An HPV intravaginal prime/boost with different HPV serotypes induced 10-fold more cervicovaginal antigen-specific CD8+ T cells than priming alone. Antigen-specific T cell numbers decreased only 2-fold after 6 months. Most genital antigen-specific CD8+ T cells were intra- or subepithelial, expressed ?E-integrin CD103, produced IFN-? and TNF-?, and displayed in vivo cytotoxicity. Using a sphingosine-1-phosphate analog (FTY720), we found that the primed CD8+ T cells proliferated in the cervicovaginal mucosa upon HPV intravaginal boost. Intravaginal HPV prime/boost reduced cervicovaginal viral titers 1,000-fold after intravaginal challenge with vaccinia virus expressing the CD8 epitope M2. In contrast, intramuscular prime/boost with an adenovirus type 5 vector induced a higher level of systemic CD8+ T cells but failed to induce intraepithelial CD103+CD8+ T cells or protect against recombinant vaccinia vaginal challenge. Thus, HPV vectors are attractive gene-delivery platforms for inducing durable intraepithelial cervicovaginal CD8+ T cell responses by promoting local proliferation and retention of primed antigen-specific CD8+ T cells.
Cuburu, Nicolas; Graham, Barney S.; Buck, Christopher B.; Kines, Rhonda C.; Pang, Yuk-Ying S.; Day, Patricia M.; Lowy, Douglas R.; Schiller, John T.
Human papillomavirus (HPV) is the most frequently diagnosed sexually transmitted infection in the United States. It is associated with the development of cervical, anal-genital, and oral-pharyngeal cancers. The rate of HPV infection among adolescents and young adults in the United States remains high, and completion rates of an HPV vaccine series remain low. At an urban pediatric clinic, adolescent and young adult participants aged 11 to 22 years (n = 37) received text message reminders for their second and third dose of HPV vaccine over an 8-month study period. Of the participants receiving text message reminders, 14% completed the vaccine series at the optimal time, whereas 0% of an interested group (n = 43) and only 3% of a standard care group (n = 232) completed the vaccine series at the optimal time. Findings support the use of text message reminders to improve HPV vaccine series completion rates in a pediatric practice. PMID:24200295
Matheson, Elaine C; Derouin, Anne; Gagliano, Martha; Thompson, Julie A; Blood-Siegfried, Jane
... type 1 (see 'Likelihood of recurrence' above). Polymerase chain reaction (PCR) test — The polymerase chain reaction (PCR) test is a very sensitive test ... genital herpes are often advised to keep a supply of antiviral medication in their home, which they ...
This review summarizes new treatments from the last seven years employed for the treatment of genital warts caused by human papillomavirus (HPV). Imquimod 3.75% is a new agent with fewer side effects and perhaps a better dosing schedule than imquimod 5%, but is not more effective. Sinecatechins/Polyphenon E 15%, a novel extract from green tea can be effective against genital warts but requires three times a day dosing and is not more effective than existing treatments; the treatment course is 12-16 weeks. Photodynamic therapy combined with other destructive modalities might increase the cure rate for genital warts. The quadrivalent vaccine against HPV 6, 11, 16, 18 is decreasing the incidence of warts in the western world but the evidence does not support vaccination as a treatment for those already infected by HPV. Hyperthermia and immunomodulators might be positive additions to the armamentarium of clinicians. In sum, there are new tools that physicians can use but none is really a great advance over what was available a decade ago. PMID:24011309
The role of human papillomavirus (HPV) infection in penile carcinoma (PeC) is currently reported and about half of the PeC is associated with HPV16 and 18. We used a PCR-based strategy by using HPV general primers to analyze 86 penile carcinomas paraffin-embedded tissues. Some clinical data, the histological subtype, growth pattern, and differentiation degree were also collected. The amplified fragments were then sequenced to confirm the HPV type and for HPV16/18 variants. DNA samples were also subjected to relative real time PCR for hTERC gene copy number. Some clinical data were also collected. Global HPV frequency was 77.9%. Relative contributions was for HPV16 (85%), 31 (4.4%), 11 (4.4%), 58, 33, 18, and 59 (1.4% each one). Sequence analysis of HPV16 identified European variants and Asian-American (AAb-c) variants in 92% and in 8% of the samples, respectively. Furthermore hTERC gene amplification was observed in only 17% of the cases. Our results suggest that some members of HPV A9 group (represented by HPV16, 58, and 31) are the most frequent among PeC patients studied with an important contribution from HPV16 European variant. The hTERC gene amplification could be poorly related to penile epithelial tissue.
Lopez-Romero, Ricardo; Iglesias-Chiesa, Candela; Alatorre, Brenda; Vazquez, Karla; Pina-Sanchez, Patricia; Alvarado, Isabel; Lazos, Minerva; Peralta, Raul; Gonzalez-Yebra, Beatriz; Romero, AnaE; Salcedo, Mauricio
Background Seropositivity to HPV16 and 18 antibodies is used as a measure of cumulative HPV exposure and as a stratifier of HPV exposure for vaccine efficacy analyses. Overall performance of these assays, as a measure of HPV exposure, has not been evaluated. Methods Using data from the enrollment phase of the HPV16/18 vaccine trial in Costa Rica, we evaluated the performance of the polyclonal ELISA HPV16 and 18 serological assays as a measure of HPV exposure. Biological (for eg. HPV infection at the cervix) and behavioral characteristics (for eg. lifetime number of sexual partners) with known associations with current and past HPV infection were used to define cases and controls (HPV exposed vs. not exposed). Pre-vaccination serum was measured for antibodies against HPV16 and HPV18 by ELISA; cervical samples were tested for HPV DNA using PCR SPF10/LiPA25. ELISA results were analyzed using receiver-operator-characteristic curves (ROC); performance was evaluated at the manufacturer set cutpoint (HPV16 =8, HPV18 =7) and at cutpoints chosen to optimize sensitivity and specificity (HPV16 =34, HPV18 =60). Results Defining cases as type-specific HPV DNA positive with high-grade abnormal cytolzogy (i.e. combined molecular and microscopic markers of infection), HPV16-ELISA gave sensitivity that was lower at the optimal cutpoint than the manufacturer cutpoint (62.2 compared with 75.7, respectively; p=0.44). However, specificity was higher (85.3 compared with 70.4, respectively; p<0.0001). Similarly, HPV18-ELISA gave sensitivity that was lower at the optimal cutpoint than the manufacturer cutpoint (34.5 compared with 51.7, respectively; p=0.40), with higher specificities (94.9 compared with 72.6, respectively; p<0.0001). Conclusions Modifying cutpoints did not improve the low sensitivity. The low sensitivity of this assay does not support its use for risk stratification or clinical settings.
Coseo, Sarah E.; Porras, Carolina; Dodd, Lori E.; Hildesheim, Allan; Rodriguez, Ana Cecilia; Schiffman, Mark; Herrero, Rolando; Wacholder, Sholom; Gonzalez, Paula; Sherman, Mark E.; Jimenez, Silvia; Solomon, Diane; Bougelet, Catherine; van Doorn, Leen-Jan; Quint, Wim; Safaeian, Mahboobeh
DNA from two novel HPV genotypes, HPV-150 and HPV-151, isolated from hair follicles of immuno-competent individuals, was fully cloned, sequenced and characterized. The complete genomes of HPV-150 and HPV-151 are 7,436-bp and 7,386-bp in length, respectively. Both contain genes for at least six proteins, namely E6, E7, E1, E2, L2, L1, as well as a non-coding upstream regulatory region located between the L1 and E6 genes: spanning 416-bp in HPV-150 (genomic positions 7,371 to 350) and 322-bp in HPV-151 (genomic positions 7,213 to 148). HPV-150 and HPV-151 are phylogenetically placed within the Betapapillomavirus genus and are most closely related to HPV-96 and HPV-22, respectively. As in other members of this genus, the intergenic E2-L2 region is very short and does not encode for an E5 gene. Both genotypes contain typical zinc binding domains in their E6 and E7 proteins, but HPV-151 lacks the regular pRb-binding core sequence within its E7 protein. In order to assess the tissue predilection and clinical significance of the novel genotypes, quantitative type-specific real-time PCR assays were developed. The 95% detection limits of the HPV-150 and HPV-151 assays were 7.3 copies/reaction (range 5.6 to 11.4) and 3.4 copies/reaction (range 2.5 to 6.0), respectively. Testing of a representative collection of HPV-associated mucosal and cutaneous benign and malignant neoplasms and hair follicles (total of 540 samples) revealed that HPV-150 and HPV-151 are relatively rare genotypes with a cutaneous tropism. Both genotypes were found in sporadic cases of common warts and SCC and BCC of the skin as single or multiple infections usually with low viral loads. HPV-150 can establish persistent infection of hair follicles in immuno-competent individuals. A partial L1 sequence of a putative novel HPV genotype, related to HPV-150, was identified in a squamous cell carcinoma of the skin obtained from a 64-year old immuno-compromised male patient.
Kovanda, Anja; Kocjan, Bostjan J.; Luzar, Bostjan; Bravo, Ignacio G.; Poljak, Mario
OBJECTIVE: We assessed the clinical, histological, and virological features of anogenital human papillomavirus (HPV) infection, according to their immune status in HIV-1 infected men, referred for an anogenital examination or treatment, in comparison with immunocompetent patients. METHODS: The study population comprised 33 HIV-1 infected heterosexual or homosexual men and 38 HIV negative men seen in a screening and treatment centre for anogenital HPV infections. All patients were examined with a colposcope. Biopsies were carried out on all subjects with anogenital lesions for histological studies and HPV detection by Southern blot. RESULTS: The HIV infected patients had a balanopreputial HPV infection in 70%, anal in 30%, and urethral in 37%, while HIV negative patients had balanopreputial lesion in 72%, anal in 26%, and urethral in 16%. Diffuse anogenital lesions were present in 33% of the HIV infected cases and in 10.5% of HIV negative cases (p < 0.02). Among the HIV infected patients, the genital HPV lesions were condylomatous in 67.5% of the cases and dysplastic in 57%. HIV negative patients had condylomatous lesions in 86% of the cases and dysplasic in 14%. The condylomatous lesions of HIV infected patients had a low grade malignant histological aspect in 36% of the cases and high grade histological criteria were found in 22% of the dysplasias. Oncogenic HPVs were detected more frequently in HIV infected patients (35% v 12%) and more than one HPV type was found in 21.5% of cases. Neither the anogenital diffusion of the HPV lesions nor their morphological, histological, and virological features differed significantly in patient with CD4 cell counts > or < 200 x 10(6)/l. In contrast, patients with CD4 cell counts < 50 x 10(6)/l had a higher risk of several types of HPVs and of developing a diffuse anogenital infection. CONCLUSION: HIV-1 infected patients had an increased frequency of high grade anogenital dysplastic lesions and a higher frequency of HPV infection with multiple and diffuse sites of involvement. These characteristics of HPV infection were independent of the patients' immune status up to CD4 cell counts > 50 x 10(6)/l but showed an increased risk when the CD4 cell count was < 50 x 10(6)/l. The higher frequency of diffuse anogenital infections among HIV infected men calls for rapid treatment, laser or surgery, given the association of histological features of intraepithelial neoplasia and the presence of multiple HPV infection sites which may be the consequence of immune disturbances, most of which are transmissible potentially oncogenic HPVs. ???
Aynaud, O.; Piron, D.; Barrasso, R.; Poveda, J. D.
Digital squamous cell carcinoma (SCC) presents a diagnostic challenge because of its relatively rare occurrence and mimicry of benign conditions. Although low-risk human papillomavirus (HPV) subtypes are commonly associated with benign digital verrucae, digital SCC can be associated with high-risk, oncogenic HPV subtypes. We report 7 patients, including 4 HIV-positive patients, who presented with 10 lesions of digital SCC in situ. Six of 10 lesions were typed for HPV by immunostain or polymerase chain reaction. Multiple high-risk oncogenic subtypes were found, including HPV-16, -33, -51, and -73. The majority of reports linking HPV and digital SCCs have implicated the HPV-16 subtype. This case series highlights the diversity of oncogenic HPV types that may be associated with digital SCCs. Because the high rate of recurrence of digital SCCs may be a result of persistence of oncogenic HPV at the margins of resection, aggressive treatment of individual lesions and of genital reservoirs for HPV on patients and their sexual partners is warranted. PMID:20584560
Gormley, Rachel H; Groft, Caroline M; Miller, Christopher J; Kovarik, Carrie L
At present it is unknown whether the higher prevalence of human papillomavirus (HPV) infection among smokers in men is attributed to a higher probability of acquiring an infection or because of longer infection persistence. Thus, we investigated the role of smoking on the incidence (acquisition) and clearance (persistence) of genital HPV infections among 4,026 men in the HPV in Men (HIM) Study, a multinational prospective study of the natural history of genital HPV infection in men. Genital HPV infections were grouped by any, oncogenic and nononcogenic HPV infections and smoking status was categorized as current, former and never smokers. The incidence of any, oncogenic and nononcogenic HPV infections was significantly higher among current smokers compared to former and never smokers (p?0.01). In multivariable analyses adjusting for sexual behavior and potential confounders, when compared to never smokers, current smokers exhibited significantly higher probability of acquiring any [hazard ratio (HR)?=?1.23; 95% confidence interval (CI) 1.02-1.50] and nononcogenic (HR?=?1.21; 95% CI 1.00-1.45) infections and a borderline significant probability for oncogenic infections (HR?=?1.18; 95% CI 0.98-1.41). Although the median duration of HPV infection was generally longer among current smokers, we found no statistically significant associations in the multivariable analyses. Overall, these results demonstrated that current smoking exhibited the highest incidence and highest probability of acquiring genital HPV infections. PMID:24222514
Schabath, Matthew B; Villa, Luisa L; Lin, Hui-Yi; Fulp, William J; Lazcano-Ponce, Eduardo; Salmerón, Jorge; Abrahamsen, Martha E; Papenfuss, Mary R; Quiterio, Manuel; Giuliano, Anna R
Vaccines prevent HPV-associated cancer but, although these tumors express foreign, viral antigens (E6 and E7 proteins), they have little benefit in established malignancies, likely due to negative environmental cues that block tumor recognition and induce T cell anergy in vivo. We postulated that we could identify mechanisms by which ex vivo stimulation of T cells could reactivate and expand tumor-directed T-cell lines from HPV-positive cancer patients for subsequent adoptive immunotherapy. A total of 68 patients with HPV-associated cancers were studied. Peripheral blood T cells were stimulated with monocyte-derived dendritic cells loaded with pepmixes (peptide libraries of 15-mers overlapping by 11 amino-acids) spanning E6/E7, in the presence or absence of specific accessory cytokines. The resulting T-cell lines were further expanded with pepmix-loaded activated B-cell blasts. IFN? release and cytotoxic responses to E6/E7 were assessed. We successfully reactivated and expanded (>1200-fold) E6/E7-specific T cells from 8/16 cervical and 33/52 oropharyngeal cancer patients. The presence of the cytokines IL-6, -7, -12 and -15 is critical for this process. These T cell lines possess the desirable characteristics of polyclonality, multiple T-cell subset representation (including the memory compartment) and a TH1 bias, and may eliminate E6/E7-positive targets. In conclusion, we have shown it is possible to robustly generate HPV16 E6/E7-directed T-cell lines from patients with HPV16-associated cancers. Because our technique is scalable and good-manufacturing-procedures compliant, these lines could be used for adoptive cellular immunotherapy of patients with HPV16-positive cancers.
Ramos, Carlos A.; Narala, Neeharika; Vyas, Gayatri M.; Leen, Ann M.; Gerdemann, Ulrike; Sturgis, Erich M.; Anderson, Matthew L.; Savoldo, Barbara; Heslop, Helen E.; Brenner, Malcolm K.; Rooney, Cliona M.
Background: The objective of this study was to investigate the expression of human papilloma virus (HPV) L1 capsid protein in abnormal cervical cytology with HPV16 infection and analyze its association with cervical histopathology in Korean women. Material and Methods: We performed immunocytochemistry for HPV L1 in 475 abnormal cervical cytology samples from patients with HPV16 infections using the Cytoactiv® HPV L1 screening set. We investigated the expression of HPV L1 in cervical cytology samples and compared it with the results of histopathological examination of surgical specimens. Results: Of a total of 475 cases, 188 (39.6%) were immunocytochemically positive and 287 (60.4%) negative for HPV L1. The immunocytochemical expression rates of HPV L1 in atypical squamous cells of unknown significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), and cancer were 21.8%, 59.7%, 19.1%, and 0.0%, respectively. LSIL exhibited the highest rate of HPV L1 positivity. Of a total of 475 cases, the multiple-type HPV infection rate, including HPV16, in HPV L1-negative cytology samples was 27.5%, which was significantly higher than that in HPV L1-positive cytology samples (p = 0.037). The absence of HPV L1 expression in ASCUS and LSIL was significantly associated with high-grade (?cervical intraepithelial neoplasia [CIN] 2) than low-grade (?CIN1) histopathology diagnoses (p < 0.05), but was not significantly different between HPV16 single and multiple-type HPV infections (p > 0.05). On the other hand, among 188 HPV L1-positive cases, 30.6% of multiple-type HPV infections showed high-grade histopathology diagnoses (?CIN3), significantly higher than the percentage of HPV16 single infections (8.6%) (p = 0.0004) Conclusions: Our study demonstrates that the expression of HPV L1 is low in advanced dysplasia. Furthermore, the absence of HPV L1 in HPV16-positive low-grade cytology (i.e., ASCUS and LSIL) is strongly associated with high-grade histopathology diagnoses. The multiplicity of HPV infections may have an important role in high-grade histopathology diagnoses (?CIN3) in HPV L1-positive cases.
Lee, Sung-Jong; Lee, Ah-Won; Kang, Chang-Suk; Park, Jong-Sup; Park, Dong-Choon; Ki, Eun-Young; Lee, Keun-Ho; Yoon, Joo-Hee; Hur, Soo-Young; Kim, Tae-Jung
Background: Persistent infection with high-risk types of human papillomavirus (HPV) is associated with cervical and other anogenital cancers. Purpose: This paper reports results of awareness of an HPV diagnosis and HPV knowledge from a multi-site study of HPV knowledge, attitudes and behavior, and the impact of an HPV diagnosis on women and their…
McCree, Donna Hubbard; Daley, Ellen M.; Gorbach, Pamina; Hamm, Robert M.; Sharpe, Patricia A.; Brandt, Heather M.; McFarlane, Mary; Kerndt, Peter; McDermott, Robert J.; Perrin, Karen M.; St. Lawrence, Janet S.
HPV infection in the genital tract is common in young sexually active individuals, the majority of whom clear the infection without overt clinical disease. However most of those who develop benign lesions eventually mount an effective cell mediated immune (CMI) response and the lesions regress. Failure to develop effective CMI to clear or control infection results in persistent infection and, in the case of the oncogenic HPVs, an increased probability of progression to CIN3 and invasive carcinoma. The prolonged duration of infection associated with HPV seems to be associated with effective evasion of innate immunity thus delaying the activation of adaptive immunity. Natural infections in animals show that neutralising antibody to the virus coat protein L1 is protective suggesting that this would be an effective prophylactic vaccine strategy. The current prophylactic HPV VLP vaccines are delivered i.m. circumventing the intra-epithelial immune evasion strategies. These vaccines generate high levels of antibody and both serological and B cell memory as evidenced by persistence of antibody and robust recall responses. However there is no immune correlate - no antibody level that correlates with protection. Recent data on how HPV infects basal epithelial cells and how antibody can prevent this provides a mechanistic explanation for the effectiveness of HPV VLP vaccines.
Photodynamic Diagnosis (PDD) and Therapy (PDT) are modern methods which are evaluated in different fields in gynaecology. PDT has been successfully evaluated in human papillomavirus-related (HPV) genital dysplasia like CIN and VIN. The aim of this review is to give an overview about current applications. PMID:20230987
Soergel, Philipp; Hillemanns, Peter
Keratoacanthoma (KA) is a clinically distinct, rapidly growing lesion that generally presents as a solitary crateriform nodule in sun-exposed areas in elderly, fair-skinned individuals. A KA larger than 20-30 mm is referred to as giant keratoacanthoma, a relatively rare lesion especially in young patients. Such lesions grow rapidly with possible destruction of underlying tissues. In addition to ultraviolet exposure, KAs have also been associated with chemical carcinogens, chemical peels, genetic factors, chronic skin conditions that produce scarring, trauma and thermal burns. Immunosuppressed patients, especially after transplantation, also develop KAs. A viral etiology has been suggested but not confirmed. We encountered a case of giant keratoacanthoma (greater than 50 mm in diameter) with induration of underlying structures on the upper lip of a 39-year-old male sailor. The patient reported sudden appearance and rapid enlargement of the lesion in only three weeks. Biopsy of the cutaneous lesion and the characteristic clinical history suggested the diagnosis of keratoacanthoma. Total excision with primary closure of the defect by a nasolabial advancement flap was performed. Histological examination of the tumor mass confirmed the diagnosis of KA with infiltrative growth and perineural invasion. Immunosuppression was excluded by blood analyses, as were HIV, syphilis and hepatitis infections. Only low-risk genital HPV type 6 was detected in the lesion, suggesting a possible cocarcinogenic effect of HPV and UV light in a chronically sun-exposed patient. PMID:16683389
Saftic, Marina; Batinac, Tanja; Zamolo, Gordana; Coklo, Miran; Simat, Marina; Mustac, Elvira; Bosnar, Alan; Grahovac, Blazenka
Prevention of HPV-associated cancers can take two forms-one through prevention of infection via prophylactic HPV vaccination, and one through interruption of disease progression through early identification (i.e.: screening) and treatment. Primary prevention via vaccination seems promising, as a proof-of-principal study demonstrated high vaccine efficacy against one-time detection of oral HPV16/18 infection. In addition to the direct benefit of vaccination, indirect protection from reduced genital HPV infection should also reduce oral HPV exposure at the individual level. Yet, for the current unvaccinated cohorts who will bear the burden of non-cervical HPV-associated cancers for the foreseeable future, no secondary prevention opportunities exist, as the field has not yet validated any screening methods for non-cervical HPV associated cancers. Serum HPV16 E6 antibody data suggest that this test might one day be able to detect many of the at-risk patients prior to tumor development. For any biomarker that proves valid and reliable, transitioning into clinical practice will require additional research focused on (1) diagnostics, (2) effective intervention, and (3) observed reductions in cancer mortality. PMID:23876626
Kreimer, Aimée R
Human papillomavirus (HPV) type 16 and 18 viral genomes are frequently detected in cervical and penile cancer biopsies. Although this strongly suggests a prominent role for HPV infection in the development of genital cancer, other genetic or environmental factors are also involved. Genital cancer is postulated to result from loss of cellular control functions, which leads to an unregulated expression of HPV oncogenic proteins. In our study, we determined the trans-activating properties of nuclear proto-oncogene proteins c-Fos, c-Jun and c-Myc on P97 enhancer/promoter activity of HPV16. Using a CAT-reporter construct containing the HPV16 enhancer/promoter element, we investigated the trans-activating effects of c-Fos, c-Jun, c-Myc, and E2 in cervical HT-3 cells. c-Fos and c-Jun overexpression resulted in a 3.3- and 3.1-fold up-regulation of CAT activity. Only 2-fold induction was determined by co-transfection with c-myc and the viral transcription factor E2. Based on these findings, we investigated the expression of HPV DNA (16 and 18) as well as nuclear proto-oncogenes (c-fos, c-jun and c-myc) in nine cervical cancers by in situ hybridisation. In six out of nine carcinomas, HPV16 and/or HPV18 DNA was detectable. All tumours showed an intense and homogeneous expression of c-fos and c-jun mRNA, while the signal for c-myc was detectable only in four specimens. These data suggest that deregulation of nuclear proto-oncogene expression may contribute to an overexpression of HPV-derived oncogenic proteins (E6 and E7), which is generally hypothesised to be an important step in the malignant transformation of HPV-associated tumours. Images Figure 2 Figure 3 Figure 4
Nurnberg, W.; Artuc, M.; Vorbrueggen, G.; Kalkbrenner, F.; Moelling, K.; Czarnetzki, B. M.; Schadendorf, D.
In this observer-blind study (NCT00423046), women (N = 1,106), stratified by age (18–26, 27–35, 36–45 y), were randomized (1:1) to receive the HPV-16/18 vaccine (Cervarix®, GlaxoSmithKline Biologicals, Months 0, 1, 6) or the HPV-6/11/16/18 vaccine (Gardasil® Merck and Co., Inc., Months 0, 2, 6). Month 7 results were previously reported; we now report Month 24 results. In the according-to-protocol cohort for immunogenicity (seronegative and DNA-negative at baseline for HPV type analyzed), seropositivity rates of neutralizing antibodies (nAbs) [pseudovirion-based neutralization assay] were, across all age strata, 100% (HPV-16/18 vaccine) and 97.5–100% (HPV-6/11/16/18 vaccine) for HPV-16, and 99.0–100% (HPV-16/18 vaccine) and 72.3–84.4% (HPV-6/11/16/18 vaccine) for HPV-18. Corresponding geometric mean titers (GMTs) were 2.4–5.8-fold higher for HPV-16 and 7.7–9.4-fold higher for HPV-18 with the HPV-16/18 vaccine vs. the HPV-6/11/16/18 vaccine; HPV-16 and HPV-18 GMTs were significantly higher with the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (p < 0.0001) in the total vaccinated cohort (received ?1 vaccine dose, irrespective of baseline sero/DNA-status). Similar results were obtained using enzyme-linked immunosorbent assay (ELISA ). Positivity rates and GMTs of antigen-specific IgG antibodies in cervicovaginal secretions (ELISA) were not significantly different between vaccines. At Month 24, CD4+ T-cell responses for HPV-16 and HPV-18 were higher with the HPV-16/18 vaccine; memory B-cell response was higher for HPV-18 with the HPV-16/18 vaccine and similar between vaccines for HPV-16. Both vaccines were generally well tolerated. Although an immunological correlate of protection has not been defined, differences in the magnitude of immune response between vaccines may represent determinants of duration of protection.
Baron, Mira; Levin, Myron J; Chatterjee, Archana; Fox, Bradley; Scholar, Sofia; Rosen, Jeffrey; Chakhtoura, Nahida; Meric, Dorothee; Dessy, Francis J; Datta, Sanjoy K; Descamps, Dominique; Dubin, Gary
Vaccination with papillomavirus L2 has been shown to induce neutralizing antibodies that protect against homologous type infection and cross-neutralize a limited number of genital HPVs. Surprisingly, we found that antibodies to bovine papillomavirus (BPV1) L2 amino acids 1-88 induced similar titers of neutralizing antibodies against Human papillomavirus (HPV)16 and 18 and BPV1 pseudoviruses and also neutralized HPV11 native virions. These antibodies also neutralized each of the other pseudovirus types tested, HPV31, HPV6 and Cottontail rabbit papillomavirus (CRPV) pseudoviruses, albeit with lower titers. HPV16, HPV18, HPV31, HPV6 and CRPV L2 anti-sera also displayed some cross-neutralization, but the titers were lower and did not encompass all pseudoviruses tested. This study demonstrates the presence of broadly cross-neutralizing epitopes at the N-terminus of L2 that are shared by cutaneous and mucosal types and by types that infect divergent species. BPV1 L2 was exceptionally effective at inducing cross-neutralizing antibodies to these shared epitopes. PMID:15885736
Pastrana, Diana V; Gambhira, Ratish; Buck, Christopher B; Pang, Yuk-Ying S; Thompson, Cynthia D; Culp, Timothy D; Christensen, Neil D; Lowy, Douglas R; Schiller, John T; Roden, Richard B S
Oral acyclovir was evaluated for its effectiveness in treating guinea pigs with primary herpes simplex virus type 2 infections. Guinea pigs inoculated intravaginally with acyclovir-susceptible strains (for which 50% inhibitory concentrations of acyclovir in cell culture were found to be in the range of 0.15 to 1.2 micrograms/ml) and treated with 5.0 mg of acyclovir per ml in the drinking water beginning 48 h postinfection showed significant reductions in lesion severity. This dosage produced serum acyclovir levels of 1.3 micrograms/ml. Lower concentrations of oral acyclovir (less than or equal to 2.5 mg/ml in the drinking water), which produced serum acyclovir levels of less than 1.0 microgram/ml, were less consistently effective against these same virus strains. When an acyclovir-resistant isolate (for which the 50% inhibitory concentration of acyclovir in cell culture was found to be 8.5 micrograms/ml) was used to initiate infection, treatment with 5 or 10 mg/ml (yielding serum levels of 1.3 and 3.5 micrograms/ml) in the drinking water had only minimal clinical benefit. However, the degree of response was difficult to determine because of the attenuated disease produced by the acyclovir-resistant virus. In vitro virus sensitivity may be predictive of the serum drug levels that need to be obtained to produce a successful response to therapy.
Ellis, M N; Barry, D W
Background Studies suggest that testing for individual HPV genotypes can improve risk stratification in women with minor cytological abnormalities. We evaluated genotyping for HPV16, HPV16/18, and HPV16/18/45 in carcinogenic HPV-positive women with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) cytology. Methods For women enrolled in the ASCUS-LSIL Triage Study (ALTS), we calculated the age-stratified (<30 and 30+ years) positivity, and cumulative risk over two years of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) when testing positive or negative for three genotype combinations: HPV16, HPV16/18, and HPV16/18/45. Results Among women with ASCUS cytology, HPV16 positivity was 17.1% and increased to 22.0% (P<.001) for HPV16/18 and 25.6% (P<.001) for HPV16/18/45. Among women with LSIL cytology, HPV16 positivity was 21.1% and increased to 30.0% (P<.001) for HPV16/18 and 34.0% (P=.017) for HPV16/18/45. Regardless of cytology and age group, the greatest risk difference between test-positives and test-negatives was observed for HPV16 with decreasing risk stratification for HPV16/18 and HPV16/18/45. However, testing negative for any of the three combinations while being positive for another carcinogenic type still implied a 2-year risk of CIN3+ of 7.8% or greater. Conclusions Although genotyping for HPV16, 18, and 45 provided additional risk stratification in carcinogenic HPV-positive women with minor cytological abnormalities, the risk among genotype-negative women was still high enough to warrant immediate colposcopy referral. Impact HPV genotyping in HPV-positive women with minor cytological abnormalities will likely not alter clinical management. Adding HPV45 to genotyping assays is not warranted.
Gage, Julia C.; Schiffman, Mark; Solomon, Diane; Wheeler, Cosette M.; Gravitt, Patti E.; Castle, Philip E.; Wentzensen, Nicolas
We present a review of current cervical cancer screening practices, the implementation status of vaccination against human papillomaviruses (HPV) and available data concerning the burden of HPV infection and HPV type-specific distribution in 16 Central and Eastern European countries: Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Montenegro, Poland, Romania, Serbia, Slovakia, Slovenia and the Former Yugoslav Republic (FYR) of Macedonia. Since published data were relatively scarce, two detailed surveys were conducted during August-October 2011 and in January 2013 to obtain relevant and updated information. The mean prevalence of HPV infection in 8610 women with normal cervical cytology from the region was 12.6%, with HPV16 being the most frequent HPV type. The overall HPV DNA prevalence in women with high-grade cervical lesions was 78.1%. HPV DNA was found in 86.6% of cervical cancers; the combined prevalence of HPV16/18 among HPV positive cases was 87.5%. The overall HPV DNA prevalence in genital warts and laryngeal papillomas was 94.8% and 95.2%, respectively, with HPV6 and HPV11 being the most frequent types. Opportunistic and organized cervical screening, mainly based on conventional cytology, is performed in nine and seven countries in the region, respectively, with the proposed age of the start of screening ranging from 20 to 30 years and the estimated coverage ranging from a few percent to over 70%. At least one of the current HPV prophylactic vaccines is registered in all Central and Eastern European countries except Montenegro. Only Bulgaria, Czech Republic, FYR Macedonia, Latvia, Romania and Slovenia have actually integrated HPV vaccination into their national immunization programme and currently provide routine vaccination free of charge to the primary target population. The key reasons for lack of implementation of HPV vaccination into the national immunization programme are high vaccine cost and negative public perception. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in the Central and Eastern Europe and Central Asia Region" Vaccine Volume 31, Supplement 7, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. PMID:24332298
Poljak, Mario; Seme, Katja; Maver, Polona J; Kocjan, Boštjan J; Cuschieri, Kate S; Rogovskaya, Svetlana I; Arbyn, Marc; Syrjänen, Stina
Abstract Objective: To characterize genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) using pooled data from Phase 3 studies. Research design and methods: Genital mycotic infections with canagliflozin 100 and 300?mg were evaluated in Population 1 (N?=?2313; mean exposure [weeks]: canagliflozin, 24.3; placebo, 23.8), including patients from four placebo-controlled studies, and Population 2 (N?=?9439; mean exposure [weeks]: canagliflozin, 68.1; control, 64.4), including patients from eight placebo/active-controlled studies (including older patients and those with renal impairment or high cardiovascular disease risk). Clinical trial registration: ClinicalTrials.gov, NCT01081834; NCT01106625; NCT01106677; NCT01106690; NCT01032629; NCT01064414; NCT01106651; NCT00968812. Main outcome measures: Adverse events suggestive of genital mycotic infections were recorded, with additional information collected using supplemental electronic case report forms. Results: In Population 1, genital mycotic infection incidence was higher with canagliflozin 100 and 300?mg than placebo (95% confidence intervals excluded zero) in females (10.4%, 11.4%, 3.2%) and males (4.2%, 3.7%, 0.6%). These were generally mild to moderate in intensity, none were serious, and few led to discontinuation. Most events with canagliflozin were treated with antifungal therapies, and median symptom duration following treatment initiation was similar across groups; few patients had >1 event (females, 2.3%; males, 0.9%). Findings with canagliflozin 100 and 300?mg versus control were similar in Population 2 (females: 14.7%, 13.9%, 3.1%; males: 7.3%, 9.3%, 1.6%); a low proportion of males underwent circumcision across groups. Most events with canagliflozin occurred within the first 4 months in females and first year in males; no consistent evidence of dose dependence was observed. Key limitations included lack of laboratory confirmation for most events and variable treatment methods. Conclusions: Genital mycotic infection incidences were higher with canagliflozin than control in patients with T2DM; events were generally mild to moderate in intensity and responded to standard treatments. PMID:24517339
Nyirjesy, Paul; Sobel, Jack D; Fung, Albert; Mayer, Cristiana; Capuano, George; Ways, Kirk; Usiskin, Keith
The goal of our study was to determine whether recombinant interleukin-2 (rIL-2) could modify the recurrence pattern of chronic herpes simplex virus type 2 (HSV-2) genital infection in guinea pigs. Animals that developed symptomatic acute HSV-2 infection were distributed at 14 days after viral inoculation into several treatment groups, which were similar with respect to the severity of acute disease. Three rIL-2 dosages administered for 4 weeks in daily subcutaneous injections were tested in this study: 5 X 10(3), 5 X 10(4), and 2.5 X 10(5) U. Daily observations of the animals showed a significant decrease of the incidence of new recurrent lesions with the use of 5 X 10(4) U of rIL-2 (rate of recurrence, 0.08, compared with 0.21 in untreated controls), whereas the other rIL-2 regimens did not affect the overall rate of recurrence. Weekly analysis of recurrences showed that treatment with 5 X 10(4) U of rIL-2 was effective only during the first 3 weeks of use and that 2.5 X 10(5) U of rIL-2 markedly decreased the rate of recurrence in the first week of treatment but not in subsequent weeks. The loss of clinical protection in both groups coincided with the production of neutralizing antibodies to rIL-2. The immune mechanisms possibly involved in the protective effect of rIL-2 in chronic HSV-2 disease were further investigated. Production of gamma interferon correlated well with clinical protection, and circulating levels dropped at the time when neutralizing antibodies to rIL-2 developed. Nonspecific cytotoxicity represented by natural killer cell and lymphokine-activated killer cell activities was also increased in the treated guinea pigs. Antibody titers and lymphocyte proliferation to herpes simplex antigen were similar in rIL-2 and placebo recipients. Finally, we found that the rIL-2-induced immune stimulation was as protective against recurrent HSV-2 disease in guinea pigs as the viral suppression achieved with acyclovir. However, the biological activity of both drugs was not additive when they were coadministered.
Weinberg, A; Konrad, M; Merigan, T C
BACKGROUND AND METHODS--We have carried out a prospective study of dual genitotropic human papillomavirus (HPV) infections by means of two different DNA detection methods in biopsy specimens obtained from patients who were examined for genital warts at the STD clinic of the School of Medicine in Seville, between January 1990 and December 1991. RESULTS--100 patients with a clinical diagnosis of condilomata acuminata were seen during the study period. DNA of the genitotropic HPV 6/11, 16/18 and 31/33/35 was detected by an in situ hybridisation method in 75 (77%) of the 98 evaluable samples; one of the genotypes tested in 59 (61%) samples, and two or more genotypes tested in the remaining 16 (15%) samples. In 21 (98%) of the 23 negative samples by in situ hybridisation, we were able to detect DNA of genital HPV using a polymerase chain reaction amplification method (PCR). Among the 34 samples where PCR was applied we confirmed the presence of two different HPV genotypes in eight samples. CONCLUSIONS--The frequency of dual infections with human genitotropic papillomavirus in genital warts was 8%, although we believe that this rate should be higher as we have not used the PCR method in all of the samples.
Aznar, J; Ojeda, A; Torres, M J; Palomares, J C; Rodriguez-Pichardo, A
Genital herpes simplex virus (HSV) infections are common but results from vaccine trials with HSV-2 glycoprotein D (gD) have been disappointing. We therefore compared a similar HSV gD2 vaccine, to a further truncated gD2 vaccine, to a vaccine with gD2 plus gB2 and gH2/gL2 and to a vaccine with only gB2 and gH2/gL2 in a guinea pig model of genital herpes. All vaccines were administered with cationic liposome-DNA complexes (CLDC) as an adjuvant. All vaccines significantly decreased the severity of acute genital disease and vaginal virus replication compared to the placebo group. The majority of animals in all groups developed at least one episode of recurrent disease but the frequency of recurrent disease was significantly reduced by each vaccine compared to placebo. No vaccine was significantly more protective than gD2 alone for any of the parameters described above. No vaccine decreased recurrent virus shedding. When protection against acute infection of dorsal root ganglia and the spinal cord was evaluated all vaccines decreased the per cent of animal with detectable virus and the quantity of virus but again no vaccine was significantly more protective than another. Improvements in HSV-2 vaccines may require inclusion of more T cell targets, more potent adjuvants or live virus vaccines.
Bernstein, David I; Earwood, Julie D.; Bravo, Fernando J.; Cohen, Gary H; Eisenberg, Roselyn J; Clark, Jennifer R.; Fairman, Jeffrey; Cardin, Rhonda D.
The novel human papillomavirus type 154 (HPV154) was characterized from a wart on the crena ani of a three-year-old boy. It was previously designated as the putative HPV type FADI3 by sequencing of a subgenomic FAP amplicon. We obtained the complete genome by combined methods including rolling circle amplification (RCA), genome walking through an adapted method for detection of integrated papillomavirus sequences by ligation-mediated PCR (DIPS-PCR), long-range PCR, and finally by cloning of four overlapping amplicons. Phylogenetically, the HPV154 genome clustered together with members of the proposed species Gammapapillomavirus 11, and demonstrated the highest identity in L1 to HPV136 (68.6%). The HPV154 was detected in 3% (2/62) of forehead skin swabs from healthy children. In addition, the different detection sites of 62 gammapapillomaviruses were summarized in order to analyze their tissue tropism. Several of these HPV types have been detected from multiple sources such as skin, oral, nasal, and genital sites, suggesting that the gammapapillomaviruses are generalists with a broader tissue tropism than previously appreciated. The study expands current knowledge concerning genetic diversity and tropism among HPV types in the rapidly growing gammapapillomavirus genus.
Ure, Agustin Enrique; Forslund, Ola
HPV is the commonest sexually transmitted viral infection in the United Kingdom and as such poses a major public health problem. In addition to the potential physical morbidity associated with genital warts, abnormal cervical cytology, and anogenital dysplasia and neoplasia, the associated psychological morbidity should not be forgotten. Although our knowledge of viral function and disease pathogenesis has advanced appreciably in recent years, we are still some way from developing an in vitro method of viral propagation. Vaccination against HPV infection will hopefully be achieved within the next 10 years, but a prevention and treatment strategy which is appropriate for both developed and developing nations must be our major long term goal.
The human papillomavirus (HPV) minor capsid protein L2 is a promising candidate for a broadly protective HPV vaccine yet the titers obtained in most experimental systems are rather low. Here we examine the potential of empty AAV2 particles (AAVLPs), assembled from VP3 alone, for display of L2 epitopes to enhance their immunogenicity. Insertion of a neutralizing epitope (amino acids 17–36) from L2 of HPV16 and HPV31 into VP3 at positions 587 and 453, respectively, permitted assembly into empty AAV particles (AAVLP(HPV16/31L2)). Intramuscularly vaccination of mice and rabbits with AAVLP(HPV16/31L2)s in montanide adjuvant, induced high titers of HPV16 L2 antibodies as measured by ELISA. Sera obtained from animals vaccinated with the AAVLP(HPV16/31L2)s neutralized infections with several HPV types in a pseudovirion infection assay. Lyophilized AAVLP(HPV16/31L2) particles retained their immunogenicity upon reconstitution. Interestingly, vaccination of animals that were pre-immunized with AAV2 - simulating the high prevalence of AAV2 antibodies in the population - even increased cross neutralization against HPV31, 45 and 58 types. Finally, passive transfer of rabbit antisera directed against AAVLP(HPV16/31L2)s protected naïve mice from vaginal challenge with HPV16 pseudovirions. In conclusion, AAVLP(HPV16/31L2) particles have the potential as a broadly protective vaccine candidate regardless of prior exposure to AAV.
Nieto, Karen; Weghofer, Margit; Sehr, Peter; Ritter, Mirko; Sedlmeier, Sebastian; Karanam, Balasubramanyam; Seitz, Hanna; Muller, Martin; Kellner, Markus; Horer, Markus; Michaelis, Uwe; Roden, Richard B. S.; Gissmann, Lutz; Kleinschmidt, Jurgen A.
Squamous cell carcinomas account for over 90 % of cancers of the oral cavity in France. Alcohol and tobacco are the main risk factors. Delay in diagnosis is unfortunately frequent. The management of the cancer is based on surgery, possibly associated to radiation therapy and chemotherapy. The survival rate at 5 years does not exceed 30-40%. We hope to see a decrease in the number of oral cancer thanks to the development of preventive medicine (alcohol and tobacco cessation and early detection of potentially malignant lesions). Vulvar squamous cell carcinoma is a rare disease which traditionally affect elderly woman but continues to rise in incidence especially in younger women. There are at least 2 forms of genital squamous cell carcinoma. The most common form is found on older women arising in a background of lichen sclerosus and the second is associated with "high risk" human papillomavirus infection affecting younger women. A biopsy is usually required for diagnosis. Attempts to reduce genital cancer must focus on treating precursor lesions, namely lichen sclerosus and HPV-related intraepithelial neoplasia (VIN and PIN). Most genital cancer occur on undiagnosed or untreated lichens sclerosus, vulvar inspection when women attend for their cervical smears or seeking about significance of any chronic genital symptom by a clinical examination. PMID:24167879
Dehen, Laure; Schwob, Emilie; Pascal, Francis
The vaginal swabs among HIV-positive women in Africa often revealed opportunistic infections such as human Papillomavirus (HPV) and Mycoplasma that induce respectively cervix cancer and diseases such as vaginosis, abortions, infertility in through salpingitis. The purposes of this study were to: (1) seek for, the prevalence of pathogens such as HPV and Mycoplasma; (2) characterize the strains of HPV and estimate their prevalence; (3) identify among these women, those who were co-infected by these pathogens in order to cure them. From February 2009 to January 2010, 156 HIV-positive women attending our medical centers and aged from 19-45 years (mean age 33.65 +/- 5.75 years) had voluntarily accepted vaginal specimen's tests. PCR, ELISA and molecular hybridization were used for the identification and characterization of these pathogens. The results revealed the presence of Mycoplasma and HPV in 25.64 and 58.33% cases, respectively. The following HPV genotypes and the following prevalence were recorded: HPV-50'S (24.11%), HPV-18 (21.28%), HPV-30'S (18.44%) and HPV-16 (5.67%). The study also enable the identification of co-infections such as HPV-18 strains with HPV-30'S (5.67%) and HPV-30'S with HPV-50'S (3.55%). Other germs infecting the female genital tract including Candida albicans (20.51%), Escherichia coli (12.18%), Treponema pallidum (3.85%), Streptococcus agalactiae (3.21%) and Staphylococcus aureus (1.92%) were isolated. This preliminary research work showed the incidence of several genital pathogens, this could be a springboard for nationwide epidemiological study on HPV strains circulating in Burkina Faso. PMID:21313918
Sagna, T; Djigma, F; Zeba, M; Bisseye, C; Karou, S D; Ouermi, D; Pietra, V; Gnoula, C; Sanogo, K; Nikiema, J B; Simpore, J
Background:We assessed the accuracy of self-collected human papillomavirus (HPV) specimens in men compared with clinician-collected specimens from men in British Columbia and determined the prevalence of HPV subtypes at different male genital sites.Methods:Heterosexual men were recruited at the Provincial Sexually Transmitted Infection (STI) Clinic in Vancouver, Canada. Participants were randomly assigned to conduct self-collection or clinician-collected specimens first. Clinicians obtained
G S Ogilvie; D L Taylor; M Achen; D Cook; M Krajden
A human papillomavirus (HPV) vaccine consisting of virus-like particles (VLPs) was recently approved for human use. It is generally assumed that VLP vaccines protect by inducing type-specific neutralizing antibodies. Preclinical animal models cannot be used to test for protection against HPV infections due to species restriction. We developed a model using chimeric HPV capsid/cottontail rabbit papillomavirus (CRPV) genome particles to permit the direct testing of HPV VLP vaccines in rabbits. Animals vaccinated with CRPV, HPV type 16 (HPV-16), or HPV-11 VLPs were challenged with both homologous (CRPV capsid) and chimeric (HPV-16 capsid) particles. Strong type-specific protection was observed, demonstrating the potential application of this approach. PMID:17005666
Mejia, Andres F; Culp, Timothy D; Cladel, Nancy M; Balogh, Karla K; Budgeon, Lynn R; Buck, Christopher B; Christensen, Neil D
Female genital tuberculosis is an uncommon type of tuberculosis that can lead to infertility. The present review describes the disease, reports available epidemiological data, and focuses on examinations and procedures necessary for the early diagnosis and the management of this curable disease. PMID:21438789
Neonakis, Ioannis K; Spandidos, Demetrios A; Petinaki, Efthimia
Persistent high-risk human papillomavirus (HR-HPV) infection is the strongest risk factor for high-grade cervical precancer. We performed a systematic review and meta-analysis of HPV persistence patterns worldwide. Medline and ISI Web of Science were searched through January 1, 2010 for articles estimating HPV persistence or duration of detection. Descriptive and meta-regression techniques were used to summarize variability and the influence of study definitions and characteristics on duration and persistence of cervical HPV infections in women. Among 86 studies providing data on over 100,000 women, 73% defined persistence as HPV positivity at a minimum of two time points. Persistence varied notably across studies and was largely mediated by study region and HPV type, with HPV-16, 31, 33 and 52 being most persistent. Weighted median duration of any-HPV detection was 9.8 months. HR-HPV (9.3 months) persisted longer than low-risk HPV (8.4 months), and HPV-16 (12.4 months) persisted longer than HPV-18 (9.8 months). Among populations of HPV-positive women with normal cytology, the median duration of any-HPV detection was 11.5 and HR-HPV detection was 10.9 months. In conclusion, we estimated that approximately half of HPV infections persist past 6 to 12 months. Repeat HPV testing at 12-month intervals could identify women at increased risk of high-grade cervical precancer due to persistent HPV infections. PMID:22961444
Rositch, Anne F; Koshiol, Jill; Hudgens, Michael G; Razzaghi, Hilda; Backes, Danielle M; Pimenta, Jeanne M; Franco, Eduardo L; Poole, Charles; Smith, Jennifer S
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. PMID:24283440
Giannaki, Maria; Kakourou, Talia; Theodoridou, Maria; Syriopoulou, Vassiliki; Kabouris, Marios; Louizou, Eirini; Chrousos, George
BACKGROUND: Human papillomavirus (HPV) and HIV are each responsible for a considerable burden of disease. Interactions between these infections pose substantial public health challenges, especially where HIV prevalence is high and HPV vaccine coverage low. METHODS: Between July 2005 and January 2006, a cross-sectional community-based survey in Mombasa, Kenya, enrolled female sex workers using snowball sampling. After interview and a
Davy Vanden Broeck; Matthew F Chersich; Annalene Nel; Wim Delva; Kishor Mandaliya; Christophe E Depuydt; Patricia Claeys; John-Paul Bogers; Marleen Temmerman
Background The epidemiology of high-risk (hr) HPV infections in mid-adult women with new sex partners is undefined. Methods We analyzed baseline data from 518 25–65 year old female online daters. Women were mailed questionnaires and kits for self-collecting vaginal specimens for PCR-based hrHPV testing. Risk factors for infection were identified using Poisson regression models to obtain prevalence ratios (PRs). Results 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 Pap test history (PR=1.42, 95% CI:1.10–1.84), lifetime number of sex partners >14 (relative to 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 Pap history and lifetime number of partners). Compared to sexually inactive women, the likelihood of infection increased with increasing risk level, (from low-risk to high-risk partners) (p<.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). Conclusions Measures of both cumulative and recent sexual history were associated with prevalent hrHPV infection in this high-risk cohort of mid-adult women.
Winer, Rachel L.; Hughes, James P.; Feng, Qinghua; Xi, Long Fu; Lee, Shu-Kuang; O'Reilly, Sandra F.; Kiviat, Nancy B.; Koutsky, Laura A.
Human papillomavirus (HPV) L1 VLP-based vaccines are protective against HPV vaccine-related types; however, the correlates of protection have not been defined. We observed that vaccination with Cervarix™ induced cross-neutralizing antibodies for HPV types for which evidence of vaccine efficacy has been demonstrated (HPV31/45) but not for other types (HPV52/58). In addition, HPV31/45 cross-neutralizing titers showed a significant increase with number of doses (HPV31, p<0.001; HPV45, p<0.001) and correlated with HPV16/18 neutralizing titers, respectively. These findings raise the possibility that cross-neutralizing antibodies are effectors of cross-protection observed for the HPV16/18 vaccine.
Kemp, Troy J.; Hildesheim, Allan; Safaeian, Mahboobeh; Dauner, Joseph G.; Pan, Yuanji; Porras, Carolina; Schiller, John T.; Lowy, Douglas R.; Herrero, Rolando; Pinto, Ligia A.
Background High-risk strains of human papillomavirus (HPV) cause cervical cancer. American Indian (AI) women in the Northern Plains of the U.S. have significantly higher incidence and mortality rates for cervical cancer than White women in the same geographical area. We compared HPV prevalence, patterns of HPV types, and infection with multiple HPV types in AI and White women living in South Dakota, U.S. Methods We analyzed the HPV status of cervical samples collected in 2006-2008 from women aged 18-65 years who attended two rural AI reservation clinics (n = 235) or an urban clinic in the same area serving mostly White women (n = 246). Data collection occurred before HPV vaccination was available to study participants. HPV DNA was amplified by using the L1 consensus primer system and an HPV Linear Array detection assay to identify HPV types. We used chi-square tests to compare HPV variables, with percentages standardized by age and lifetime number of sexual partners. Results Compared to White women, AI women were younger (p = 0.01) and reported more sexual partners (p < 0.001). A lower percentage of AI women tested negative for HPV infection compared to Whites (58% [95% CI = 51-65] vs. 77% [95% CI = 71-82]; p < 0.001), and a higher percentage of AI women were infected by oncogenic types (30% [95% CI = 25-36] vs. 16% [95% CI = 11-21]; p = 0.001). Infections among AI women showed a wider variety and very different pattern of HPV types, including a higher prevalence of mixed HPV infections (19% [95% CI = 26-38] vs. 7% [95% CI = 4-11]; p = 0.001). AI women had a higher percentage of HPV infections that were not preventable by HPV vaccination (32% [95% CI = 26-38] vs. 15% [95% CI = 11-21]; p < 0.001). Conclusions A higher HPV burden and a different HPV genotyping profile may contribute to the high rate of cervical cancer among AI women.
In developed countries including Japan, cervical cancer tends to affect younger woman who may be responsible for young children. Cervical cancer is the second most common cancer in the world. Therefore, the social consequences of the disease can be still tremendous. For cervical cancer prevention, vaccination programs against the two major cancer-causing types (HPV-16/18) started in the world. There are two licensed HPV vaccines; Gardasil (HPV-6/11/16/18) and Cervarix (HPV-16/18). Clinical trials have shown that these vaccines are almost 100% effective in preventing high-grade precancer associated with the HPV types and that these vaccines are safe, well tolerated and highly immunogenic. In 26 countries, universal vaccination of females between 9 and 15 years is recommended and 65-100% of the cost of the vaccine is paid for by the state. We all look with eager anticipation towards the prospects of HPV vaccines and the perspective of eradicating cervical cancer in the not too distant future. PMID:20218332
Papillomaviruses are small DNA viruses that infect and multiply in cutaneous or mucosal epithelial tissue. Human papillomavirus (HPV) 16 and 18 cause more than 99% of cervical carcinomas. Simultaneous presence of HPV is found in cervical intraepithelial neoplasia, vaginal intraepithelial neoplasia, vaginal and anal cancer. Invasive vulvar squamous cell carcinoma in younger women under the age of 50 are also associated with HPV. Most of the penile lesions are subclinical and the high prevalence of high-risk HPV suggests that they constitute a reservoir for high-risk HPV. Bowens disease and Buschke-Lowenstein tumors are associated with particular low- and high-risk HPV types. The potential role of HPV infection in the carcinogenic steps of breast, prostate, colorectal and lung cancers should be further tested. HPV-DNA might be transported from the original site of infection to the breast tissue by the bloodstream, and therefore is possibly involved in the carcinogenesis of breast neoplasia in some patients. HPV-DNA is detected in 40-70% of head and neck squamous cell carcinomas and in only 1% in normal epithelial cells. In this paper we propose the hypothesis that many epithelial normal cells are susceptible to HPV infection, which are the most sexually transmitted viruses. Experimental and epidemiological data imply a causative role for HPVs and they appear to be the second most important risk factor for cancer development in humans, exceeded only by tobacco usage. PMID:19810128
Georgieva, St; Iordanov, V; Sergieva, S
In surveillance for cervical neoplasia, a diagnosis of cytologically atypical squamous cells of undetermined significance (ASCUS) presents a significant clinical issue, often dependent on testing for high-risk (HR) human papillomavirus (HPV) for the triage of patients. HPV type 16 now appears to be a critical concern in the follow-up of patients with ASCUS. The Invader HPV (Inv2) test, by Third Wave Technologies, Inc., is a recently developed analyte-specific reagent assay that uses probe sets for the detection of 14 HR HPV subtypes. These probe sets are A5/A6 (HPV types 51, 56, and 66), A7 (HPV types 18, 39, 45, 59, and 68), and A9 (HPV types 16, 31, 33, 35, 52, and 58). This report describes the performance characteristics of the Inv2 test in the screening of ASCUS cervical cytology specimens and correlates the results of the Inv2 test with those of the Hybrid Capture II HPV (HC2) test by Digene. The linear array HPV genotyping test (Roche Molecular Systems) was used as a reference method for the testing of samples with discordant results. Ninety-four Pap smear samples with a cytological diagnosis of ASCUS and 39 samples with a negative diagnosis were tested. The results of the Inv2 test demonstrated a good (86.6%) concordance with those of the HC2 test, with an overall sensitivity and specificity of 96% for the Inv2 test. Additionally, the Inv2 assay, which offers high-throughput, semiautomated DNA extraction, allows the subgrouping of HPV types by differential probe sets, could provide a useful test for screening for HPV, and has the potential to provide an improved means of risk stratification and the selection of patients for further HPV subtyping.
Wong, Anna K.; Chan, Raymond C.-K.; Nichols, W. Stephen; Bose, Shikha
Recently, the studies on the prevention and treatment of human papillomavirus (HPV) which is closely related to the cervical cancer and other genital diseases are attracting more and more attention all over the world. Marine-derived polysaccharides and other bioactive compounds have been shown to possess a variety of anti-HPV and related cancer activities. This paper will review the recent progress in research on the potential anti-HPV and related cancer agents from marine resources. In particular, it will provide an update on the anti-HPV actions of heparinoid polysaccharides and bioactive compounds present in marine organisms, as well as the therapeutic vaccines relating to marine organisms. In addition, the possible mechanisms of anti-HPV actions of marine bioactive compounds and their potential for therapeutic application will also be summarized in detail.
Wang, Shi-Xin; Zhang, Xiao-Shuang; Guan, Hua-Shi; Wang, Wei
Abstract HIV-1 genital shedding is associated with increased HIV-1 transmission risk. Inflammation and ulceration are associated with increased shedding, while highly active antiretroviral therapy (HAART) has been shown to have a protective effect. We sought to examine the impact of cervical biopsies, a routine component of cervical cancer screening, on HIV-1 genital RNA levels in HIV-infected women on HAART. We enrolled HIV-1-infected women undergoing cervical biopsy for diagnosis of cervical intraepithelial neoplasia (CIN) 2/3 in this prospective cohort study. All were stable on HAART for at least 3 months. Clinical and demographic information as well as plasma HIV-1 viral load were collected at the baseline visit. Specimens for cervical HIV-1 RNA were collected immediately prior to biopsy, and 2 and 7 days afterward. Quantitative PCR determined HIV-1 concentration in cervical specimens at each time point to a lower limit of detection of 40 copies/specimen. Among the 30 participants, five (16.6%) women had detectable cervical HIV-1 RNA at baseline, of whom four (80%) had detectable HIV-1 RNA after cervical biopsy, with no significant increase in viral load in the follow-up specimens. Only one woman (3.3%) with undetectable baseline cervical HIV-1 RNA had detection postbiopsy. Detectable plasma HIV-1 RNA was the only factor associated with baseline cervical HIV-1 RNA. In women on HAART, an increase in cervical HIV-1 RNA detection or concentration was not associated with cervical biopsy. These findings help provide safety data regarding cervical cancer screening and diagnosis in HIV-infected women and inform postprocedure counseling.
Woo, Victoria G.; Liegler, Teri; Cohen, Craig R.; Sawaya, George F.; Smith-McCune, Karen; Bukusi, Elizabeth A.
... cancers—types 16 and 18. Women in the Costa Rica HPV Vaccine Trial who received the Cervarix vaccine ... researchers tested samples from women participating in the Costa Rica HPV Vaccine Trial, a clinical trial of Cervarix ...
Human papillomavirus (HPV) infection has been demonstrated in some of the nonmelanoma skin cancers as well as in precancerous lesions. Multiple infections of mucosal high-risk HPV may contribute to the onset of digital Bowen's disease through, if any, digital-genital transmission. We screened for the presence of the mucosal HPV DNA in patients with extragenital Bowen's disease (n = 30), squamous cell carcinoma (n = 11), bowenoid papulosis (n = 9), verrucous carcinoma (n = 1), actinic keratosis (n = 5), and basal cell carcinoma (n = 5). We used a PANArray HPV Genotyping Chip for high-risk and low-risk mucosal types. Genotyping data was confirmed using a conventional direct DNA sequencing method. Two cases of extragenital Bowen's disease were positive for types 16 and 33 of mucosal HPV, respectively. None of the squamous cell carcinoma cases were positive. Neither patients with digital Bowen's disease (n = 5) nor those with squamous cell carcinoma (n = 3) showed any mucosal high-risk HPV. Mucosal high-risk HPV DNA was confirmed in 5 (55.6%) of the 9 patients with bowenoid papulosis. HPV 16 was most prevalent (n = 3), while the DNA of HPVs 35 and 67 was detected in one sample for each of the two types. Our study demonstrated that two (6.7%) of the patients with 30 extragenital Bowen's disease were positive for types 16 and 33 of mucosal HPV, respectively. HPVs belonging to the mucosal high-risk group may participate in the development of extragenital Bowen's disease. However, we could not find any relationship between the mucosal high-risk HPV and Bowen's disease or squamous cell carcinoma in the fingers.
Park, Hye-Rim; Kim, Kwang Ho; Seo, Jinwon; Kim, Dong Hoon; Kwon, Mi Jung
Interleukin12 (IL12) and IL18 Are Important in Innate Defense against Genital Herpes Simplex Virus Type 2 Infection in Mice but Are Not Required for the Development of Acquired Gamma Interferon-Mediated Protective Immunity
Using a combination of gene-targeted mice and neutralizing antibodies, we showed that interleukin-12 (IL-12) and IL-18 are important in the innate control of genital herpes simplex virus type 2 infection but were not found to be critical, either singly or in combination, for the development of a protective gamma interferon- mediated immune response.
ALI M. HARANDI; BO SVENNERHOLM; JAN HOLMGREN; KRISTINA ERIKSSON
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 (?2=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.
BIAN, MEI-LU; CHENG, JIAO-YING; MA, LI; CONG, XIAO; LIU, JUN; CHEN, YING; CHEN, XI
Background Human papillomaviruses are the most common sexually transmitted infections, and genital warts, caused by HPV-6 and 11, entail considerable morbidity and cost. The natural history of genital warts in relation to HIV-1 infection has not been described in African women. We examined risk factors for genital warts in a cohort of high-risk women in Burkina Faso, in order to further describe their epidemiology. Methods A prospective study of 765 high-risk women who were followed at 4-monthly intervals for 27 months in Burkina Faso. Logistic and Cox regression were used to identify factors associated with prevalent, incident and persistent genital warts, including HIV-1 serostatus, CD4+ count, and concurrent sexually transmitted infections. In a subset of 306 women, cervical HPV DNA was tested at enrolment. Results Genital wart prevalence at baseline was 1.6% (8/492) among HIV-uninfected and 7.0% (19/273) among HIV-1 seropositive women. Forty women (5.2%) experienced at least one incident GW episode. Incidence was 1.1 per 100 person-years among HIV-uninfected women, 7.4 per 100 person-years among HIV-1 seropositive women with a nadir CD4+ count >200 cells/?L and 14.6 per 100 person-years among HIV-1 seropositive women with a nadir CD4+ count ?200 cells/?L. Incident genital warts were also associated with concurrent bacterial vaginosis, and genital ulceration. Antiretroviral therapy was not protective against incident or persistent genital warts. Detection of HPV-6 DNA and abnormal cervical cytology were strongly associated with incident genital warts. Conclusions Genital warts occur much more frequently among HIV-1 infected women in Africa, particularly among those with low CD4+ counts. Antiretroviral therapy did not reduce the incidence or persistence of genital warts in this population.
Background Human papillomavirus detection is very important for the evaluation of prevention strategies in cervical cancer. In the Azorean population, the virus prevalence has never been studied, and there is no data available to preview a successful outcome with HPV vaccination. In this article, our objective is to characterise the HPV genotypes in Terceira Island, contributing for the epidemiological knowledge on the virus infection. Results Cervical samples were collected from 289 women aged 16–81 in the Gynaecological Outpatient Clinic of the Hospital de Santo Espírito de Angra do Heroísmo (HSEAH). HPV DNA was amplified by Polymerase Chain Reaction using the general consensus primers PGMYO9/PGMY11. Commercially available Papillomavirus Clinical Arrays® kits (Genomica) were used to perform HPV genotyping. 30 women were HPV positive, with a median age of 41 years old. Our results show that the overall HPV prevalence was 10.49%. Seventeen genotypes were identified, including 58.82% high risk, 17.65% low risk and 23.53% undetermined risk. Conclusion Unlike other epidemiological studies, HPV31 was the most frequent type (26.67%) in Terceira Island, followed by HPV16 (10.00%), HPV51, HPV53, HPV70 and HPV82 (6.67%). Further studies are needed to investigate if the HPV types found in our population are associated with the risk of progression to high-grade squamous intraepithelial lesions or cervical cancer.
Dutra, Isa; Santos, Margarida R; Soares, Marta; Couto, Ana R; Bruges-Armas, Maria; Teixeira, Fernando; Monjardino, Luisa; Hodgson, Shirley; Bruges-Armas, Jacome
Objective To assess whether vaccination against human papillomavirus (HPV) increases the risk of miscarriage. Design Pooled analysis of two multicentre, phase three masked randomised controlled trials Setting Multicentre trials in several continents and in Costa Rica. Participants 26?130 women aged 15-25 at enrolment; 3599 pregnancies eligible for analysis. Interventions Participants were randomly assigned to receive three doses of bivalent HPV 16/18 VLP vaccine with AS04 adjuvant (n=13?075) or hepatitis A vaccine as control (n=13?055) over six months. Main outcome measures Miscarriage and other pregnancy outcomes. Results The estimated rate of miscarriage was 11.5% in pregnancies in women in the HPV arm and 10.2% in the control arm. The one sided P value for the primary analysis was 0.16; thus, overall, there was no significant increase in miscarriage among women assigned to the HPV vaccine arm. In secondary descriptive analyses, miscarriage rates were 14.7% in the HPV vaccine arm and 9.1% in the control arm in pregnancies that began within three months after nearest vaccination. Conclusion There is no evidence overall for an association between HPV vaccination and risk of miscarriage. Trial registration Clinical Trials NCT00128661 and NCT00122681.
Regional differences in human papillomavirus (HPV) genotypes and the presence of mixed HPV infections may affect adversely the efficacy of the HPV vaccine. Therefore, a simple and high-throughput HPV genotyping system is required. Recently, a novel HPV genotyping kit (the Mebgen™ HPV kit) was developed. This kit uses multiplex PCR and Luminex xMAP™ technology to detect 13 types of high-risk HPVs and an internal control in a 96-well format. In the present study, the analytical performance of the kit was examined using HPV plasmid DNA. All 13 types of HPVs were detected with a minimum detection sensitivity of 250 copies/test, and highly specific signals were observed. HPV 16 plasmid was detected in samples containing mixtures with other HPV-type plasmids in ratios ranging from 1:1 to 1:1000. No cross reactivity was observed with DNA from 27 types of other infectious microbes. A clinical evaluation was carried out using cervical samples from 356 patients with persistent abnormal smears diagnosed at mass public health screenings for cervical cancer. The samples were preserved in Tacas™ medium until analysis. HPV was detected in 162 (45.5%) samples including 110 (67.9%) with single infections and 52 (32.1%) with multiple infections. The type distribution of the 13 high-risk HPVs was as follows: 28.4% HPV 16, 11.7% HPV 18, 6.8% HPV 31, 3.1% HPV 33, 3.7% HPV 35, 9.3% HPV 39, 1.9% HPV 45, 8.6% HPV 51, 37.0% HPV 52, 9.3% HPV 56, 16.7% HPV 58, 3.7% HPV 59, and 1.9% HPV 68. To evaluate sample stability over time, changes in the detection of HPV DNA derived from HeLa and SiHa cells were measured in 3 types of liquid-based cytology media. HPV DNA was detected in Tacas and Thinprep™ samples after storage at 4°C or 30°C for 4 weeks and within 1 week of collection in Surepath™ samples. These results suggest that this newly developed HPV genotyping kit is suitable for use in both clinical applications and large-scale epidemiological studies. PMID:24768623
Ozaki, Satoru; Kato, Kana; Abe, Yukiko; Hara, Hirotaka; Kubota, Hiroshi; Kubushiro, Kaneyuki; Kawahara, Ei; Inoue, Masaki
The identification of high-risk human papillomavirus (HPV) types as a necessary cause of cervical cancer offers the prospect of effective primary prevention and the possibility of improving the efficiency of cervical screening programmes. However, for these opportunities to be realized, a more complete understanding of the natural history of HPV infection, and its relationship to the development of epithelial abnormalities
Stuart I. Collins; Lawrence S. Young; Ciaran B. J. Woodman
Objective To study the difference in gene expression between human papillomavirus (HPV)-positive and HPV-negative oral squamous cell carcinoma (OSCC). Design We used Affymetrix U133 plus 2.0 arrays to examine gene expression profiles of OSCC and normal oral tissue. HPV DNA was detected using PCR followed by the Roche Linear Array HPV Genotyping Test, and the differentially expressed genes were analyzed to examine their potential biological roles using the Ingenuity Pathway Analysis Software (IPA 5.0). Subjects Tumor tissue from 119 primary OSCC patients and normal oral tissue from 35 patients without cancer, all of whom were treated at three University of Washington-affiliated medical centers. Results HPV DNA was found in 41 of 119 (34.5%) tumors and 2 of 35 (5.7%) normal tissue samples, with 39 of 43 HPV being HPV type 16; there was a higher prevalence of HPV DNA in oropharyngeal cancer (23 of 31) than in oral cavity cancer (18 of 88). We found no significant difference in gene expression between HPV-positive and HPV-negative oral cavity cancer but found 446 probe sets (347 known genes) differentially expressed between HPV-positive and HPV-negative oropharyngeal cancer. The most prominent functions of these genes are DNA replication, DNA repair, and cell cycle. Some genes differentially expressed between HPV-positive and HPV-negative oropharyngeal cancer (e.g., TYMS, STMN1, CCND1 and RBBP4) are involved in chemotherapy or radiation sensitivity. Conclusion These results suggest that differences in the biology of HPV-positive and HPV-negative oropharyngeal cancer may have implications for the management of patients with these different tumors.
Lohavanichbutr, Pawadee; Houck, John; Fan, Wenhong; Yueh, Bevan; Mendez, Eduardo; Futran, Neal; Doody, David R.; Upton, Melissa P.; Farwell, D. Gregory; Schwartz, Stephen M.; Zhao, Lue Ping; Chen, Chu
Background. Infection with and persistence of high-risk human papillomavirus (HR-HPV) are the strongest risk factors for cervical cancer. In addition, other genital microorganisms may also be involved in the progression of HPV-associated lesions. Objetive. To evaluate the association of the vaginal microbiota (Candida spp., Trichomonas vaginalis, and bacterial vaginosis) with HR-HPV infection in Spanish female sex workers (FSWs). Methods. This cross-sectional study involved 208 (FSWs; age, 18–49 years) who visited a sexually transmitted infection (STI) information and prevention center (SERGAS) between January 2010 and December 2011. Face-to-face interviews were carried out. Cervical and vaginal samples were examined for human papillomavirus (HPV), Trichomonas vaginalis, Candida spp., and microorganisms related to bacterial vaginosis (BV). Results. HR-HPV was found to be significantly associated with BV in FSWs with positive results for HPV16-related types (31, 33, 35, and 52). T. vaginalis was isolated in FSWs with the following HR-HPVs: 18, 45, 66, and 68. Candida spp. were isolated only in FSWs with HPV 18-positive infection. Conclusion. We demonstrate a significant prevalence of HR-HPVs in FSWs with disturbances in the vaginal microbiota.
Rodriguez-Cerdeira, C.; Sanchez-Blanco, E.; Alba, A.
... of which are meant to remove the visible warts. There is no cure for genital warts. Gardasil® is a vaccine that protects against the ... Treatments Your Physician May Prescribe There is no cure for genital warts. The goal of treatment is to remove visible ...
Human papillomavirus (HPV) is the causative agent of cervical cancer, the second most common cause of cancer death in women worldwide. The licensed HPV vaccine Gardasil® from Merck & Co. is a quadrivalent vaccine containing virus-like particles (VLPs) of the L1 proteins from HPV types 6, 11, 16, and 18 adsorbed on aluminum salts (alum). CIA07 is an immunostimulatory agent
Ji Eun Han; Hye Kyeong Kim; Shin Ae Park; Seung Jae Lee; Hyoung Jin Kim; Ga Hyun Son; Young Tae Kim; Yang Je Cho; Hong-Jin Kim; Na Gyong Lee
PURPOSE: High-risk human papilloma virus (HPV) plays a role in the development of a subset of vulvar squamous cell carcinomas. Uncertainty exists about the true impact of HPV in this tumor type because conflicting reports have been published with diverging prevalence rates. This study was done to fine tune the role of high-risk HPV infection in vulvar squamous cell carcinoma
H. P. van de Nieuwenhof; L. C. L. T. van Kempen; J. A. de Hullu; R. L. M. Bekkers; J. Bulten; W. J. G. Melchers; L. F. A. G. Massuger
Background: Human papillomavirus (HPV) is a very common sexually transmitted infection linked to cervical disease. Vaccines for some types of HPV were in development at the time of the study. Purpose: The study examined HPV vaccine acceptability among underserved women in a rural region of the southeastern U.S. with high rates of cervical cancer…
Brandt, Heather M.; Sharpe, Patricia A.; McCree, Donna H.; Wright, Marcie S.; Davis, Jennifer; Hutto, Brent E.
Human papillomavirus virus-like particle (HPV VLP) HPV vaccines currently evaluated for licensing are likely to be available soon. Licensure will be based on evidence that the vaccine is well tolerated and provides near complete type-specific protection against HPV infections and their resulting lesions in the first few years after vaccination. Several important questions will remain to be answered after licensure
Allan Hildesheim; Lauri Markowitz; Mauricio Hernandez Avila; Silvia Franceschi
We identified sequences from two distantly related papillomaviruses in genital warts from two Burmeister's porpoises, including a PV antigen-positive specimen, and characterized Phocoena spinipinnis papillomavirus type 1 (PsPV-1). The PsPV-1 genome comprises 7879 nt and presents unusual features. It lacks an E7, an E8 and a bona fide E5 open reading frame (ORF) and has a large E6 ORF. PsPV-1 L1 ORF showed the highest percentage of nucleotide identity (54-55 %) with human papillomavirus type 5, bovine papillomavirus type 3 (BPV-3) and Tursiops truncatus papillomavirus type 2 (TtPV-2). This warrants the classification of PsPV-1 as the prototype of the genus Omikronpapillomavirus. PsPV-1 clustered with TtPV-2 in the E6 and E1E2 phylogenetic trees and with TtPV-2 and BPV-3 in the L2L1 tree. This supports the hypothesis that PV evolution may not be monophyletic across all genes. PMID:17554024
Van Bressem, Marie-Françoise; Cassonnet, Patricia; Rector, Annabel; Desaintes, Christian; Van Waerebeek, Koen; Alfaro-Shigueto, Joanna; Van Ranst, Marc; Orth, Gérard
Hispanic women have more than a 1.5-fold increased cervical cancer incidence and mortality compared to non-Hispanic white women in the United States. The Centers for Disease Control recommends the HPV vaccine for females at ages 11 and 12 years, though it is approved for females aged 9–26 to protect against the primary types of high-risk HPV (HPV-16 and HPV-18) that cause approximately 70% of cervical cancer cases. Few culturally-tailored Spanish HPV vaccine awareness programs have been developed. This study evaluates the efficacy of a Spanish radionovela as an educational tool. Rural Hispanic parents of daughters aged 9–17 (n = 88; 78 mothers and 10 fathers) were randomized to listen to the HPV vaccine radionovela or to another public service announcement. Participants completed a 30 min pretest posttest questionnaire. Parents who listened to the HPV radionovela (intervention group) scored higher on six knowledge and belief items. They were more likely to confirm that HPV is a common infection (70% vs. 48%, P = .002), to deny that women are able to detect HPV (53% vs. 31%, P = .003), to know vaccine age recommendations (87% vs. 68%, P = .003), and to confirm multiple doses (48% vs. 26%, P = .03) than control group parents. The HPV vaccine radionovela improved HPV and HPV vaccine knowledge and attitudes. Radionovela health education may be an efficacious strategy to increase HPV vaccine awareness among Hispanic parents.
Coronado, Gloria D.; Rodriguez, Hector P.; Thompson, Beti
Human papillomavirus (HPV) causes most cases of anal cancers. In this study, we analyzed biopsy material from 112 patients with anal cancers in Australia for the presence of HPV DNA by the INNO LiPA HPV genotyping assay. There were 82% (92) males and 18% (20) females. The mean age at diagnosis was significantly (p?=?0.006) younger for males (52.5 years) than females (66 years). HIV-infected males were diagnosed at a much earlier mean age (48.2 years) than HIV negative (56.3 years) males (p?=?0.05). HPV DNA was detected in 96.4% (108) of cases. HPV type 16 was the commonest, at 75% (81) of samples and being the sole genotype detected in 61% (66). Overall, 79% (85) of cases had at least one genotype targeted by the bivalent HPV (bHPV) vaccine, 90% (97) by the quadrivalent HPV (qHPV) vaccine and 96% (104) by the nonavalent HPV (nHPV) vaccine. The qHPV vaccine, which is now offered to all secondary school students in Australia, may prevent anal cancers in Australia. However, given the mean age of onset of this condition, the vaccine is unlikely to have a significant impact for several decades. Further research is necessary to prove additional protective effects of the nHPV vaccine. PMID:24497322
Hillman, Richard J; Garland, Suzanne M; Gunathilake, Manoji P W; Stevens, Matthew; Kumaradevan, Nirmala; Lemech, Charlotte; Ward, Robyn L; Meagher, Alan; McHugh, Leo; Jin, Fengyi; Carroll, Susan; Goldstein, David; Grulich, Andrew E; Tabrizi, Sepehr N
Female genital mutilation is a common practice in many cultures, and has a range of complications. Many women in the UK have undergone the procedure and many girls are at risk. This article discusses the types of FGM and its complications, and explains how nurses can identify those who have had or are at risk of FGM and either offer support or specialist referral. PMID:24881177
The occurrence of basal cell carcinoma (BCC) of the vulva is rare. We report the case of a 79-year-old woman with a medical history of intravaginal condyloma acuminatum and vaginal intraepithelial neoplasia 3 (VaIN 3) who presented with a solitary whitish lesion sized 8x5 mm with a central desquamation located on the right labium majus. Histopathologic examination revealed a typical superficial and nodular BCC. Additionally, there were multiple remarkable foci of epidermolytic hyperkeratosis (EH). These foci both merged with superficial BCC or were sharply demarcated from the tumor. Retrospective molecular-biological examination of all the available material revealed HPV type 42 in both condyloma acuminatum and VaIN 3 specimen but not in the BCC associated with EH. To our best knowledge, involvement of the lower female genitalia by EH is a rare finding with six cases published to date. Awareness of EH in this location and its distinction is important because it may be potentially misinterpreted as a viral condyloma. Keywords: vulva - basal cell carcinoma - epidermolytic hyperkeratosis - human papillomavirus. PMID:24758505
Kacerovská, Denisa; Michal, Michal; Kašpírková, Jana; Kazakov, Dmitry V
In South Africa asymptomatic wart virus infection diagnosed by morphological criteria occurs in 16-20% of all ethnic groups; the incidence in black women is 66%. To identify human papillomavirus (HPV) types the prevalence of HPV in cervical intraepithelial neoplasia (CIN) in South African women (n = 72) with age matched British women (n = 73) was compared by non-isotopic in situ hybridisation (NISH) using digoxigenin labelled probes for HPV 6, 11, 16, 18, 31, 33 and 35 on archival biopsy specimens. A higher proportion of British biopsy specimens (68%) contained HPV than those from South Africa (50%) in CIN 2 and 3; this difference was due to HPV 16. Thirty six per cent of the positive biopsy specimens from South African women also contained HPV 33/35 compared with 16% in the United Kingdom. There was no difference in HPV detection with age in either group. These data indicate that HPV types vary geographically, with "minor" HPV types being more common in South Africa. Three qualitatively distinct NISH signals were observed; a diffuse (type 1) signal in superficial cells, mainly koilocytes; a punctate signal (type 2) in basal/"undifferentiated" cells in CIN 3; and combined type 1 and 2 signals in CIN with wart virus infection (type 3). The punctate signal may represent HPV integration. Images
Cooper, K; Herrington, C S; Graham, A K; Evans, M F; McGee, J O
Background: Information is scarce about the presence of molecular alterations related to human papillomavirus (HPV) infection in squamous cell carcinomas of the genital skin and about the effect of this infection in the number of Langerhans cells present in these tumors. Aims: To determine the presence of HPV in genital skin squamous cell carcinomas and to see the relationship between HPV infection and changes in the expression of Ki-67 antigen (Ki-67), p53 protein (p53), retinoblastoma protein (pRb) and E-cadherin and to alterations in Langerhans cell density, if any. Methods: A descriptive, comparative, retrospective and cross-sectional study was performed with all the cases diagnosed as squamous cell carcinomas of the genital skin at the Dermatopathology Service from 2001 to 2011. The diagnosis was verified by histopathological examination. The presence of HPV was examined using chromogenic in situ hybridization, and protein expression was studied via immunohistochemical analysis. Results: The 34 cases studied were verified as squamous cell carcinomas and 44.1% were HPV positive. The degree of expression of pRb was 17.50% ±14.11% (mean ± SD) in HPV-positive cases and 29.74% ±20.38% in HPV-negative cases (P = 0.0236). The degree of expression of Ki-67 was 47.67% ±30.64% in HPV-positive cases and 29.87% ±15.95% in HPV-negative cases (P = 0.0273). Conclusion: HPV infection was related to lower pRb expression and higher Ki-67 expression in comparison with HPV negative samples. We could not find a relationship between HPV infection and the degree of expression of p53 and E-cadherin or with Langerhans cell density. PMID:25035383
Rios-Yuil, Jose M; Herrera-Gonzalez, Norma E; Aguilar-Faisal, Jose L; Lara-Padilla, Eleazar; Mercadillo-Perez, Patricia; Moreno-Lopez, Luis M; Marquez-Ramirez, Alejandro K; Saldana-Patino, Azael; Rubio-Gayosso, Ivan
Human papillomavirus (HPV) causes cervical cancer and other hyperproliferative diseases. There currently are no approved antiviral drugs for HPV that directly decrease viral DNA load and that have low toxicity. We report the potent anti-HPV activity of two N-methylpyrrole-imidazole polyamides of the hairpin type, polyamide 1 (PA1) and polyamide 25 (PA25). Both polyamides have potent anti-HPV activity against three different genotypes when tested on cells maintaining HPV episomes. The compounds were tested against HPV16 (in W12 cells), HPV18 (in Ker4-18 cells), and HPV31 (in HPV31 maintaining cells). From a library of polyamides designed to recognize AT-rich DNA sequences such as those in or near E1 or E2 binding sites of the HPV16 origin of replication (ori), four polyamides were identified that possessed apparent IC(50)s?150nM with no evidence of cytotoxicity. We report two highly-active compounds here. Treatment of epithelia engineered in organotypic cultures with these compounds also causes a dose-dependent loss of HPV episomal DNA that correlates with accumulation of compounds in the nucleus. Bromodeoxyuridine (BrdU) incorporation demonstrates that DNA synthesis in organotypic cultures is suppressed upon compound treatment, correlating with a loss of HPV16 and HPV18 episomes. PA1 and PA25 are currently in preclinical development as antiviral compounds for treatment of HPV-related disease, including cervical dysplasia. PA1, PA25, and related polyamides offer promise as antiviral agents and as tools to regulate HPV episomal levels in cells for the study of HPV biology. We also report that anti-HPV16 activity for Distamycin A, a natural product related to our polyamides, is accompanied by significant cellular toxicity. PMID:21669229
Edwards, Terri G; Koeller, Kevin J; Slomczynska, Urszula; Fok, Kam; Helmus, Michael; Bashkin, James K; Fisher, Chris
Human papillomavirus (HPV) causes cervical cancer and other hyperproliferative diseases. There currently are no approved antiviral drugs for HPV that directly decrease viral DNA load and that have low toxicity. We report the potent anti-HPV activity of two N-methylpyrrole-imidazole polyamides of the hairpin type, polyamide 1 (PA1) and polyamide 25 (PA25). Both polyamides have potent anti-HPV activity against 3 different genotypes when tested on cells maintaining HPV episomes. The compounds were tested against HPV16 (in W12 cells), HPV18 (in Ker4-18 cells), and HPV31 (tested in HPV31 maintaining cells). From a library of polyamides designed to recognize AT-rich DNA sequences such as those in or near E1 or E2 binding sites of the HPV16 origin of replication (ori), 4 polyamides were identified that possessed apparent IC50s ? 150 nM with no evidence of cytotoxicity and we report two highly-active compounds here. Treatment of epithelia engineered in organotypic cultures with these compounds also causes a dose-dependent loss of HPV episomal DNA that correlates with accumulation of compounds in the nucleus. Bromodeoxyuridine (BrdU) incorporation demonstrates that DNA synthesis in organotypic cultures is suppressed upon compound treatment, correlating with a loss of HPV16 and HPV18 episomes. PA1 and PA25 are currently in preclinical development as an antiviral compound for treatment of HPV-related disease, including cervical dysplasia. PA1 and related polyamides offer promise as antiviral agents and the ability to regulate HPV episomal levels in cells for the study of HPV biology. We also report that anti-HPV16 activity for Distamycin A, a natural product related to PA1, is accompanied by significant cellular toxicity.
Edwards, Terri G.; Koeller, Kevin J.; Slomczynska, Urszula; Fok, Kam; Helmus, Michael; Bashkin, James K.; Fisher, Chris
Vulval intraepithelial neoplasia is a precursor of vulval cancer and is commonly caused by infection with Human Papillomavirus (HPV). Development of topical treatments for vulval intraepithelial neoplasia requires appropriate in vitro models. This study evaluated the feasibility of primary culture of vulval intraepithelial neoplasia biopsy tissue to produce cell lines for use as in vitro models. A potentially immortal cell line was produced which gave rise to three monoclonal lines. These lines were characterized for HPV genomic integration and for viral gene expression using ligation-mediated PCR and quantitative PCR. Distinct patterns of viral integration and gene expression were observed among the three lines. Integration and expression data were validated using deep sequencing of mRNA. Gene ontology analyses of these data also demonstrated that expression of the HPV16 E4 and E5 proteins resulted in substantial changes in the composition of the cell membrane and extracellular space, associated with alterations in cell adhesion and differentiation. These data illustrate the diverse patterns of HPV gene expression potentially present within a single lesion. The derived cell lines provide useful models to investigate the biology of vulval intraepithelial neoplasia and the interactions between different HPV gene products and potential therapeutic agents. J. Med. Virol. 86:1534-1541, 2014. © 2014 Wiley Periodicals, Inc. PMID:24898764
Bryant, Dean; Onions, Tiffany; Raybould, Rachel; Flynn, Aine; Tristram, Amanda; Meyrick, Sian; Giles, Peter; Ashelford, Kevin; Hibbitts, Samantha; Fiander, Alison; Powell, Ned
We report the characterization of three novel human papillomavirus (HPV) types of the genus Gammapapillomavirus. HPV175 and HPV180 were isolated from a condyloma. HPV178 was isolated from healthy skin adjacent to an actinic keratosis.
Background: Papillomatosis is a known histopathologic pattern usually seen in human papillomavirus (HPV) infection and verruca vulgaris is the typical example. This pattern is also detected in some other benign cutaneous lesions such as nevus sebaceous (NS), seborrheic keratosis (SK), trichilemmoma (TL) and inverted follicular keratosis (IFK). The association between papillomatous lesions and HPV infection is questionable. Objective: The objective of this study was to investigate the presence of HPV deoxyribonucleic acid (DNA) in non-genital benign papillomatous skin lesions (NS, SK, TL and IFK) by polymerase chain reaction (PCR). Materials and Methods: A total of 100 specimens of non-genital NS, SK, TL and IFK were retrieved from archives of Dermatopathology Department of Razi Hospital, between 2003 and 2010. The conventional PCR using consensus GP5+/GP6+ primer and hydroxymethylbilane synthase gene as inner control was performed. Results: PCR for HPV DNA revealed no positive results in any of 28 seborrheic keratosis (SK), 28 nevus sebaceous (NS), 28 inverted follicular keratosis (IFK) and 13 trichilemmoma (TL) studied specimens. Conclusion: Papillomatosis is usually a characteristic pattern of HPV infection. However, we found no association between HPV infection and non-genital benign papillomatous lesions.
Kambiz, Kamyab Hesari; Kaveh, Davoodi; Maede, Damavandi; Hossein, Ayatollahi; Nessa, Aghazadeh; Ziba, Rahbar; Alireza, Ghanadan
Background Human papillomavirus (HPV) infection, particularly with type 16, causes a growing fraction of oropharyngeal cancers, whose incidence is increasing, mainly in developed countries. In a double-blind controlled trial conducted to investigate vaccine efficacy (VE) of the bivalent HPV 16/18 vaccine against cervical infections and lesions, we estimated VE against prevalent oral HPV infections 4 years after vaccination. Methods and Findings A total of 7,466 women 18–25 years old were randomized (1?1) to receive the HPV16/18 vaccine or hepatitis A vaccine as control. At the final blinded 4-year study visit, 5,840 participants provided oral specimens (91·9% of eligible women) to evaluate VE against oral infections. Our primary analysis evaluated prevalent oral HPV infection among all vaccinated women with oral and cervical HPV results. Corresponding VE against prevalent cervical HPV16/18 infection was calculated for comparison. Oral prevalence of identifiable mucosal HPV was relatively low (1·7%). Approximately four years after vaccination, there were 15 prevalent HPV16/18 infections in the control group and one in the vaccine group, for an estimated VE of 93·3% (95% CI?=?63% to 100%). Corresponding efficacy against prevalent cervical HPV16/18 infection for the same cohort at the same visit was 72·0% (95% CI?=?63% to 79%) (p versus oral VE?=?0·04). There was no statistically significant protection against other oral HPV infections, though power was limited for these analyses. Conclusions HPV prevalence four years after vaccination with the ASO4-adjuvanted HPV16/18 vaccine was much lower among women in the vaccine arm compared to the control arm, suggesting that the vaccine affords strong protection against oral HPV16/18 infection, with potentially important implications for prevention of increasingly common HPV-associated oropharyngeal cancer. ClinicalTrials.gov, Registry number NCT00128661
Herrero, Rolando; Quint, Wim; Hildesheim, Allan; Gonzalez, Paula; Struijk, Linda; Katki, Hormuzd A.; Porras, Carolina; Schiffman, Mark; Rodriguez, Ana Cecilia; Solomon, Diane; Jimenez, Silvia; Schiller, John T.; Lowy, Douglas R.; van Doorn, Leen-Jan; Wacholder, Sholom; Kreimer, Aimee R.
Data from the National Disease and Therapeutic Index (NDTI) Survey indicate that the number of physician-patient consultations concerning genital herpes increased 15-fold between 1966 and 1984. Because of the increased incidence of genital herpes, the great variance in symptoms and severity of outbreaks, and the frequent misrepresentation of the nature of herpes simplex, all health-care practitioners should receive up-to-date information on the disorder. This article is intended to educate health-care professionals about genital herpes. PMID:2231078
Quadrivalent human papillomavirus (HPV) vaccine has been shown to provide protection from HPV 6/11/16/18-related cervical, vaginal, and vulvar disease through 3 years. We provide an update on the efficacy of the quadrivalent HPV vaccine against high-grade cervical, vaginal, and vulvar lesions based on end-of-study data from three clinical trials. Additionally, we stratify vaccine efficacy by several baseline characteristics, including age, smoking status, and Papanicolaou (Pap) test results. A total of 18,174 females ages 16 to 26 years were randomized and allocated into one of three clinical trials (protocols 007, 013, and 015). Vaccine or placebo was given at baseline, month 2, and month 6. Pap testing was conducted at regular intervals. Cervical and anogenital swabs were collected for HPV DNA testing. Examination for the presence of vulvar and vaginal lesions was also done. Endpoints included high-grade cervical, vulvar, or vaginal lesions (CIN 2/3, VIN 2/3, or VaIN 2/3). Mean follow-up time was 42 months post dose 1. Vaccine efficacy against HPV 6/11/16/18-related high-grade cervical lesions in the per-protocol and intention-to-treat populations was 98.2% [95% confidence interval (95% CI), 93.3-99.8] and 51.5% (95% CI, 40.6-60.6), respectively. Vaccine efficacy against HPV 6/11/16/18-related high-grade vulvar and vaginal lesions in the per-protocol and intention-to-treat populations was 100.0% (95% CI, 82.6-100.0) and 79.0% (95% CI, 56.4-91.0), respectively. Efficacy in the intention-to-treat population tended to be lower in older women, women with more partners, and women with abnormal Pap test results. The efficacy of quadrivalent HPV vaccine against high-grade cervical and external anogenital neoplasia remains high through 42 months post vaccination. PMID:19789295
Kjaer, Susanne K; Sigurdsson, Kristján; Iversen, Ole-Erik; Hernandez-Avila, Mauricio; Wheeler, Cosette M; Perez, Gonzalo; Brown, Darron R; Koutsky, Laura A; Tay, Eng Hseon; García, Patricia; Ault, Kevin A; Garland, Suzanne M; Leodolter, Sepp; Olsson, Sven-Eric; Tang, Grace W K; Ferris, Daron G; Paavonen, Jorma; Lehtinen, Matti; Steben, Marc; Bosch, F Xavier; Dillner, Joakim; Joura, Elmar A; Majewski, Slawomir; Muñoz, Nubia; Myers, Evan R; Villa, Luisa L; Taddeo, Frank J; Roberts, Christine; Tadesse, Amha; Bryan, Janine; Maansson, Roger; Lu, Shuang; Vuocolo, Scott; Hesley, Teresa M; Saah, Alfred; Barr, Eliav; Haupt, Richard M
Human papillomavirus (HPV) DNA genotyping is an essential test to establish efficacy in HPV vaccine clinical trials and HPV prevalence in natural history studies. A number of HPV DNA genotyping methods have been cited in the literature, but the comparability of the outcomes from the different methods has not been well characterized. Clinically, cytology is used to establish possible HPV infection. We evaluated the sensitivity and specificity of HPV multiplex PCR assays compared to those of the testing scheme of the Hybrid Capture II (HCII) assay followed by an HPV PCR/line hybridization assay (HCII-LiPA v2). SurePath residual samples were split into two aliquots. One aliquot was subjected to HCII testing followed by DNA extraction and LiPA v2 genotyping. The second aliquot was shipped to a second laboratory, where DNA was extracted and HPV multiplex PCR testing was performed. Comparisons were evaluated for 15 HPV types common in both assays. A slightly higher proportion of samples tested positive by the HPV multiplex PCR than by the HCII-LiPA v2 assay. The sensitivities of the multiplex PCR assay relative to those of the HCII-LiPA v2 assay for HPV types 6, 11, 16, and 18, for example, were 0.806, 0.646, 0.920, and 0.860, respectively; the specificities were 0.986, 0.998, 0.960, and 0.986, respectively. The overall comparability of detection of the 15 HPV types was quite high. Analyses of DNA genotype testing compared to cytology results demonstrated a significant discordance between cytology-negative (normal) and HPV DNA-positive results. This demonstrates the challenges of cytological diagnosis and the possibility that a significant number of HPV-infected cells may appear cytologically normal.
Iftner, Thomas; Germ, Liesje; Swoyer, Ryan; Kjaer, Susanne Kruger; Breugelmans, J. Gabrielle; Munk, Christian; Stubenrauch, Frank; Antonello, Joseph; Bryan, Janine T.; Taddeo, Frank J.
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Despite national guidelines and proven health benefits, vaccination rates for the human papillomavirus (HPV) remain far below those of other vaccines recommended for adolescents. HPV is the most common sexually transmitted infection in the U.S; it is responsible for about 25,000 new cancers each year. A series of three shots is recommended for all girls and boys at age 11-12, but significant barriers exist to starting and finishing this series. This Issue Brief examines some of the barriers and summarizes a successful, multipronged clinical intervention to improve vaccination rates. PMID:24660247
Fiks, Alexander G
Human papillomavirus (HPV) has been identified as the major cause of cervical cancer worldwide and HPV DNA testing is recommended in primary cervical cancer screening. Several molecular tests for detection/typing of HPV DNA with different sensitivity and specificity are commercially available. The present study compared the performance of the Abbott RealTime High Risk HPV assay and the Genomica HPV Clinical Array CLART2 in 78 specimens (63 cervical smears and 15 rectal/urethral swabs).The typing results of the Genomica assay were in absolute agreement with each of the four possible result categories of the Abbott assay (HPV16, HPV18, Other HR HPV, not detected) in 87.2% (68/78) of the samples, with a Cohen' kappa agreement coefficient for every HR type of 0.62 (95% CI: 0.39-0.85), higher in cervical swabs (k = 0.74, 95% CI: 0.50-0.99) than in rectal/urethral swabs (k = 0.36, 95% CI: 0.00-0.82). There was an excellent agreement of the Genomica results with those of Abbott in cervical samples harbored HPV single infection (100% agreement). Nonetheless, both methods may lose sensitivity for detecting HPV types in multiple infections, giving discordant results (10/78). This underlines the importance of establishing the analytical sensitivity in HPV type detection in single and multiple HPV infections. In rectal/urethral swabs, 5 of 15 (33%) discordant cases were observed, most of which became compatible when the Genomica assay was performed starting from nucleic acid extracted with the Abbott m2000sp system. These results suggest that nucleic extraction based on the magnetic beads technique is suitable for HPV DNA detection in urethral/rectal swabs. PMID:23398447
Sias, Catia; Garbuglia, Anna Rosa; Piselli, Pierluca; Cimaglia, Claudia; Lapa, Daniele; Del Nonno, Franca; Baiocchini, Andrea; Capobianchi, Maria Rosaria
Background Cervical cancer, a rare outcome of high-risk human papillomavirus (HPV) infection, disproportionately affects African American women, who are about twice more likely than European American women to die of the disease. Most cervical HPV infections clear in about one year. However, in some women HPV persists, posing a greater risk for cervical dysplasia and cancer. The Carolina Women’s Care Study (CWCS) was conducted to explore the biological, genetic, and lifestyle determinants of persistent HPV infection in college-aged European American and African American women. This paper presents the initial results of the CWCS, based upon data obtained at enrollment. Methods Freshman female students attending the University of South Carolina were enrolled in the CWCS and followed until graduation with biannual visits, including two Papanicolaou tests, cervical mucus collection, and a questionnaire assessing lifestyle factors. We recruited 467 women, 293 of whom completed four or more visits for a total of 2274 visits. Results and conclusion CWCS participants were 70% European American, 24% African American, 3% Latina/Hispanic, and 3% Asian. At enrollment, 32% tested positive for any HPV. HPV16 infection was the most common (18% of infections). Together, HPV16, 66, 51, 52, and 18 accounted for 58% of all HPV infections. Sixty-four percent of all HPV-positive samples contained more than one HPV type, with an average of 2.2 HPV types per HPV-positive participant. We found differences between African American and European American women in the prevalence of HPV infection (38.1% African American, 30.7% European American) and abnormal Papanicolaou test results (9.8% African-American, 5.8% European American). While these differences did not reach statistical significance at enrollment, as the longitudinal data of this cohort are analyzed, the sample size will allow us to confirm these results and compare the natural history of HPV infection in college-aged African American and European American women.
Banister, Carolyn E; Messersmith, Amy R; Chakraborty, Hrishikesh; Wang, Yinding; Spiryda, Lisa B; Glover, Saundra H; Pirisi, Lucia; Creek, Kim E
Background Reduction in the prevalence of vaccine type HPV infection in young women is an early indication of the impact of the HPV immunisation programme and a necessary outcome if the subsequent impact on cervical cancer is to be realised. Methods Residual vulva-vaginal swab (VVS) specimens from young women aged 16–24 years undergoing chlamydia screening in community sexual health services (formerly known as family planning clinics), general practice (GP), and youth clinics in 2010–2012 were submitted from 10 laboratories in seven regions around England. These specimens were linked to demographic and sexual behaviour data reported with the chlamydia test, anonymised, and tested for type-specific HPV DNA using a multiplex PCR and Luminex-based genotyping test. Estimated immunisation coverage was calculated and findings were compared to a baseline survey conducted prior to the introduction of HPV immunisation in 2008. Results A total of 4664 eligible specimens were collected and 4178 had a valid test result. The post-immunisation prevalence of HPV 16/18 infection was lowest in this youngest age group (16–18 years) and increased with age. This increase with age was a reversal of the pattern seen prior to immunisation and was inversely associated with estimates of age-specific immunisation coverage (65% for 16–18 year olds). The prevalence of HPV 16/18 infection in the post-immunisation survey was 6.5% amongst 16–18 year olds, compared to 19.1% in the similar survey conducted prior to the introduction of HPV immunisation. Conclusions These findings are the first indication that the national HPV immunisation programme is successfully preventing HPV 16/18 infection in sexually active young women in England. The reductions seen suggest, for the estimated coverage, high vaccine effectiveness and some herd-protection benefits. Continued surveillance is needed to determine the effects of immunisation on non-vaccine HPV types.
Mesher, D.; Soldan, K.; Howell-Jones, R.; Panwar, K.; Manyenga, P.; Jit, M.; Beddows, S.; Gill, O.N.
Robust evidence supports new strategies for prevention of cervical cancer based on the detection of persistent Human papillomavirus (HPV) infection, the causative agent of the disease. New HPV infection is usually benign and transient, while persistent infection with one of -high risk HPV explains almost all of these cancers. In fact, the detection of one of the 12 oncogenic HPV increase the sensitivity of the screening and predicts, sooner than cytology, the risk of precancerous lesions, the high grade of cervical intraepithelial neoplasia (HG CIN). Negative HPV detection gives instantaneously a reassurance close to 100% of absence of disease at risk (while cytology detection is less than 60%) and almost guarantees protection of the absence of HG CIN over a prolonged period, allowing lengthening safely the screening interval to 5 years. Pooled HPV-based screening tests decrease the specificity of the screening and increases the number of colposcopy. New strategies can significantly improve the specificity of HPV screening without a significant impact on the sensitivity, including exclusion of women less than 30 years, the use of HPV DNA genotyping tests with recognition of the most HPV at risk, the 16 and 18 types. HPV alone can be used as a screening tool in women of 30 years + with a cytology triage or immunocytochemical staining of cyto slides for p16 of HPV positive. Co-testing (cytology+ HPV test) was adopted in the USA as a standard screening option. PMID:24235325
Proliferating and tumour cells express the glycolytic isoenzyme, pyruvate kinase type M2 (M2-PK), which occurs in a highly active tetrameric form and in a dimeric form with low affinity for phosphoenolpyruvate. The switch between the two forms regulates glycolytic phosphometabolite pools and the interaction between glycolysis and glutaminolysis. In the present study, we show the effects of oncoprotein E7 of the human papilloma virus (HPV)-16 (E7)-transformation on two NIH 3T3 cell strains with different metabolic characteristics. E7-transformation of the high glycolytic NIH 3T3 cell strain led to a shift of M2-PK to the dimeric form and, in consequence, to a decrease in the cellular pyruvate kinase mass-action ratio, the glycolytic flux rate and the (ATP+GTP)/(UTP+CTP) ratio, as well as to an increase in fructose 1,6-bisphosphate (FBP) levels, glutamine consumption and cell proliferation. The low glycolytic NIH 3T3 cell strain is characterized by high pyruvate and glutamine consumption rates and by an intrinsically large amount of the dimeric form of M2-PK, which is correlated with high FBP levels, a low (ATP+GTP)/(CTP+UTP) ratio and a high proliferation rate. E7-transformation of this cell strain led to an alteration in the glycolytic-enzyme complex that correlates with an increase in pyruvate and glutamine consumption and a slight increase in the flow of glucose to lactate. The association of phosphoglyceromutase within the glycolytic-enzyme complex led to an increase of glucose and serine consumption and a disruption of the linkage between glucose consumption and glutaminolysis. In both NIH 3T3 cell lines, transformation increased glutaminolysis and the positive correlation between alanine and lactate production.
Mazurek, S; Zwerschke, W; Jansen-Durr, P; Eigenbrodt, E
Patients with recurrent respiratory papillomatosis (RRP) in Norway treated between 1987 and 2009 were recruited to this cohort study. They were followed from disease onset and data recorded until January 2012. Here, we describe the distribution of human papillomavirus (HPV) genotypes, the prevalence of multiple HPV infections, and the risk of high-grade laryngeal neoplasia and respiratory tract invasive carcinoma in a large cohort of patients with RRP. We also examined whether HPV genotype, gender, age or clinical course are risk factors for this development. Clinical records and histological specimens were reviewed. Using formalin-fixed paraffin-embedded biopsies, HPV genotyping were performed by quantitative polymerase chain reaction assays identifying 15 HPV types. HPV-negative specimens were analyzed by metagenomic sequencing. Paraffin blocks were available in 224/238 patients. The DNA quality was approved in 221/224 cases. HPV DNA was detected in 207/221 patients and all were HPV 6 or HPV 11 positive, comprising HPV 6 in 133/207, HPV 11 in 40/207 cases and HPV 6/11 in 15/207 cases. Co-infection with one or two high-risk HPV types together with HPV 6 or HPV 11 was present in 19/207 patients. Metagenomic sequencing of 14 HPV-negative specimens revealed HPV 8 in one case. In total, 39/221 patients developed high-grade laryngeal neoplasia. 8/221 patients developed carcinoma of the respiratory tract (six patients with laryngeal carcinoma and two patients with lung carcinoma). High-grade laryngeal neoplasias were found more frequently in HPV-negative versus HPV-positive patients, (RR?=?2.35, 95% CI 1.1, 4.99), as well as respiratory tract carcinomas (RR?=?48, 95% CI 10.72, 214.91). In summary, the majority of RRP were associated with HPV 6 and/or 11. HPV-negative RRP biopsies occurred more frequently in adult-onset patients, and were associated with an increased risk of laryngeal neoplasia and carcinoma in the respiratory tract. PMID:24918765
Omland, Turid; Lie, Kathrine A; Akre, Harriet; Sandlie, Lars Erik; Jebsen, Peter; Sandvik, Leiv; Nymoen, Dag Andre; Bzhalava, Davit; Dillner, Joakim; Brøndbo, Kjell
Patients with recurrent respiratory papillomatosis (RRP) in Norway treated between 1987 and 2009 were recruited to this cohort study. They were followed from disease onset and data recorded until January 2012. Here, we describe the distribution of human papillomavirus (HPV) genotypes, the prevalence of multiple HPV infections, and the risk of high-grade laryngeal neoplasia and respiratory tract invasive carcinoma in a large cohort of patients with RRP. We also examined whether HPV genotype, gender, age or clinical course are risk factors for this development. Clinical records and histological specimens were reviewed. Using formalin-fixed paraffin-embedded biopsies, HPV genotyping were performed by quantitative polymerase chain reaction assays identifying 15 HPV types. HPV-negative specimens were analyzed by metagenomic sequencing. Paraffin blocks were available in 224/238 patients. The DNA quality was approved in 221/224 cases. HPV DNA was detected in 207/221 patients and all were HPV 6 or HPV 11 positive, comprising HPV 6 in 133/207, HPV 11 in 40/207 cases and HPV 6/11 in 15/207 cases. Co-infection with one or two high-risk HPV types together with HPV 6 or HPV 11 was present in 19/207 patients. Metagenomic sequencing of 14 HPV-negative specimens revealed HPV 8 in one case. In total, 39/221 patients developed high-grade laryngeal neoplasia. 8/221 patients developed carcinoma of the respiratory tract (six patients with laryngeal carcinoma and two patients with lung carcinoma). High-grade laryngeal neoplasias were found more frequently in HPV-negative versus HPV-positive patients, (RR?=?2.35, 95% CI 1.1, 4.99), as well as respiratory tract carcinomas (RR?=?48, 95% CI 10.72, 214.91). In summary, the majority of RRP were associated with HPV 6 and/or 11. HPV-negative RRP biopsies occurred more frequently in adult-onset patients, and were associated with an increased risk of laryngeal neoplasia and carcinoma in the respiratory tract.
Omland, Turid; Lie, Kathrine A.; Akre, Harriet; Sandlie, Lars Erik; Jebsen, Peter; Sandvik, Leiv; Nymoen, Dag Andre; Bzhalava, Davit; Dillner, Joakim; Br?ndbo, Kjell
In order to develop a human immunodeficiency virus type 1 vaccine with global efficacy, it is important to evaluate the virus populations that are transmitted to individuals living in high-incidence areas. To determine the nature of the human immunodeficiency virus type 1 population transmitted to women during heterosexual contact, we examined the diversity of the proviral envelope gene in infected
MARY POSS; HAROLD L. MARTIN; JOAN K. KREISS; LAURA GRANVILLE; BHAVNA CHOHAN; PATRICK NYANGE; KISHORCHANDRA MANDALIYA; ANDJULIE OVERBAUGH
Background Peer influence and social networking can change female adolescent and young adult behavior. Peer influence on preferences for male human papillomavirus (HPV) vaccination has not been documented. The primary aim of this study was to determine if women had preferences about male sexual partner HPV vaccination receipt. Methods and Findings A prospective survey of women 18–26 years of age was conducted at an urban university student health clinic. Education about the two HPV vaccines, cervical cancer and genital warts was provided. Women self-reported their demographic and medical history data, as well as their own preferences for HPV vaccine and their preferences for their male partner HPV vaccine using a 5 point Likert scale. 601 women, mean age of 21.5 years (SD 2.4), participated between 2011 and 2012. Nearly 95% of respondents were heterosexual; condoms and contraceptives were used in over half of the population. Regardless of the woman's vaccination status, women had significantly higher (strongly agree/agree) preferences for the male partner being vaccinated with HPV4 than not caring if he was vaccinated (63.6% vs. 13.1%, p<0.001). This preference was repeated for sexual risk factors and past reproductive medical history. Women who received HPV4 compared to those choosing HPV2 had a significantly lower proportion of preferences for not caring if the male partner was vaccinated (13% vs. 22%, p?=?0.015). Conclusions Women preferred a HPV vaccinated male partner. Peer messaging might change the male HPV vaccination uptake.
Harper, Diane Medved; Alexander, Natalie Marya; Ahern, Debra Ann; Comes, Johanna Claire; Smith, Melissa Smith; Heutinck, Melinda Ann; Handley, Sandra Martin
Adolescents who are sexually active have the highest rates of prevalent and incident HPV infection rates with over 50-80% having infections within 2-3 years of initiating intercourse. These high rates reflect sexual behavior and biologic vulnerability. Most infections are transient in nature and cause no cytologic abnormality. However, a small number of adolescents will not clear the infection. Persistence of HPV is strongly linked to the development of high-grade squamous intra-epithelial lesions (HSIL) and invasive cancer. The HSIL detected, however, does not appear to progress rapidly to invasive cancer. Understanding the natural history of HPV in adolescents has shed light into optional treatment strategies which include watchful observation of atypical squamous cells of undetermined significance (ASCUS) and low grade (LSIL). The association between age of first intercourse and invasive cancer cannot be ignored. Consequently, initiating screening at appropriate times in this vulnerable group is essential. In addition, with the advent of the HPV vaccine, vaccination prior to the onset of sexual activity is critical since most infections occur within a short time frame post initiation. PMID:17627058
OBJECTIVE: New colposcopic protocols allow examiners to better document genital trauma in rape victims. We report our findings on the locations and types of genital injury seen in female assault victims versus women engaging in consensual sex.STUDY DESIGN: Physical examinations were performed on 311 rape victims seen by San Luis Obispo County's Suspected Abuse Response Team between 1985 and 1993
Laura Slaughter; Carl R. V. Brown; Sharon Crowley; Roxy Peck
Despite theconventional treatments of radiation therapy and chemotherapy, the five-year survival rates for patients withadvanced stage cervical cancers remain low. Cancer immunotherapy has emerged as an alternative, innovative therapythat may improve survival. Here we utilize a preclinical HPV-16 E6/E7-expressing tumor model, TC-1,and employ the chemotherapeutic agent cisplatin to generate an accumulation of CD11c+ dendritic cells in tumor loci making it an ideal location for the administration of therapeutic vaccines. Following cisplatin treatment, we tested different routes of administration of a therapeutic HPV vaccinia vaccine encoding HPV-16 E7 antigen (CRT/E7-VV).We found that TC-1tumor-bearing C57BL/6 mice treated with cisplatin and intratumoral injection of CRT/E7-VV significantly increased E7-specific CD8+ T cells in the blood and generated potent local and systemic antitumor immune responsescompared to mice receiving cisplatin and CRT/E7-VV intraperitoneally or mice treated with cisplatin alone. We further extended our study using a clinical grade recombinant vaccinia vaccine encoding HPV-16/18 E6/E7 antigens (TA-HPV).We found that intratumoral injection with TA-HPV following cisplatin treatment also led to increased E7-specific CD8+ T cells in the blood as well as significantly decreased tumor size compared to intratumoral injection with wild type vaccinia virus. Our study has strong implications for future clinical translation using intratumoralinjection of TA-HPV in conjunction with the current treatment strategies for patients with advanced cervical cancer.
Lee, Sung Yong; Kang, Tae Heung; Knoff, Jayne; Huang, Zhuomin; Soong, Ruey-Shyang; Alvarez, Ronald D.; Hung, Chien-Fu; Wu, Tzyy-Choou
Sexually transmitted diseases represent a significant cause of mortality and morbidity worldwide. The genital mucosa is the first line of defense against sexually transmitted pathogens and, like other mucosal tissues, it is colonized by resident immune cells that initiate an immune responses that can prevent the establishment and dissemination of infection. While it is clear that systemic vaccination is sufficient to provide protection against certain pathogens that infect the genital tract, such as human papillomavirus (HPV) and hepatitis B virus (HBV), it has not worked for other. Induction of local mucosal immune responses in the genital tract might increase the efficacy of vaccines targeting HSV, HIV and other sexually transmitted infections. Here, we describe recent promising efforts to induce adaptive immune responses in the genital tract using vaccines based on virus-like particles (VLPs) and pseudoviruses (PsVs).
Cuburu, Nicolas; Chackerian, Bryce
Synthetic oligonucleotides containing CpG motifs in specific sequence contexts have been shown to induce potent immune responses. We have evaluated mucosal administration of two immunostimulatory sequence (ISS)-containing phosphorothioate-stabilized oligonucleotides for antiherpetic efficacy in animal models. The ISS oligonucleotides, suspended in phosphate-buffered saline, were tested in mouse and guinea pig vaginal models of herpes simplex virus type 2 (HSV-2) infection. For
Richard B. Pyles; Debbie Higgins; Claudia Chalk; Anthony Zalar; Joseph Eiden; Carrie Brown; Gary Van Nest; Lawrence R. Stanberry
Irritant and allergic contact dermatitis is commonly seen in patients complaining of itching, burning and irritation in the genital area. The aim of this retrospective study was to establish the prevalence of allergic contact dermatitis patients with genital complaints. We followed 33 patients with persistent or recurrent genital redness, itching and burning sensation. Diagnosis was made by history, clinical examination and patch testing. Patch tests were carried out according to the International Contact Dermatitis Research Group with a standard series of allergens. We also tested topical pharmaceutical products that individual patients used for treating genital symptoms and patients self intimate hygiene products. There were 11 male and 22 female patients, mean age 38 years. Thirteen (39%) patients had one or more positive allergic reactions, mainly to nickel-sulfate, thimerosal, balsam of Peru, formaldehyde and neomycin sulfate. In seven of 13 patients with positive patch test results, these reactions were considered to be relevant to their clinical condition. Three patients had positive patch test reactions to their intimate hygiene products. One patient had positive patch test reaction to latex condom. Patients with genital symptoms are at a risk of developing contact sensitivity. Patch testing is useful in the management of these patients and many can be helped by allergen avoidance. PMID:20021983
Ljubojevi?, Suzana; Lipozenci?, Jasna; Celi?, Diana; Turci?, Petra
Background: The study was aimed to evaluate the prevalence and genotype distribution of HPV infection in vulvar squamous cell carcinoma (SCC) in northern Thailand and the clinicopathological difference with regard to HPV infection status. Materials and Methods: Formalin-fixed paraffin-embedded tissue samples of vulvar SCC diagnosed between January 2006 and December 2012 were collected. HPV infection was detected by nested polymerase chain reaction (PCR) with primers MY09/11 and GP5+/6+. HPV genotyping was performed using the Linear Array Genotyping Test, followed by type-specific PCR targeting the E6/E7 region of HPV16/18/52 if the Linear Array test was negative. The histologic slides of vulvar lesions and the medical records were reviewed. Results: There were 47 cases of vulvar SCC included in the study (mean patient age 57.9±13.2 years). HPV infection was detected in 29 cases (62%), all of which had single HPV infections. HPV16 accounted for 23 (49%). The patients with HPV-positive SCC had a significantly younger mean age than those with HPV-negative tumors (52.7 years vs 66.2 years, p<0.001). There was no significant difference in tumor stage distribution with regard to the status of HPV infection. The presence of vulvar intraepithelial neoplasia (VIN) of usual type (basaloid or warty) was significantly more frequent in HPV-positive cases compared with HPV-negative cases (62% vs 6%, p<0.001), whereas differentiated-type VIN was more common in HPV-negative cases (24% vs 0%, p=0.019). Conclusions: HPV infection was detected in 62% of vulvar SCC in northern Thailand. HPV16 was the predominant genotype similar to the data reported from other regions. HPV-positive SCC occurred in younger patients compared with HPV-negative SCC, and was associated with usual-type VIN. Vaccination against HPV16/18 may potentially prevent almost one half of vulvar SCC in northern Thailand. PMID:24870792
Siriaunkgul, Sumalee; Settakorn, Jongkolnee; Sukpan, Kornkanok; Srisomboon, Jatupol; Utaipat, Utaiwan; Lekawanvijit, Suree; Khunamornpong, Surapan
Background HPV has been found repeatedly in esophageal carcinoma tissues. However, reported detection rates of HPV DNA in these tumors have varied markedly. Differences in detection methods, sample types, and geographic regions of sample origin have been suggested as potential causes of this discrepancy. Methods HPV L1 DNA and HPV genotypes were evaluated in 435 esophageal carcinoma specimens collected from four geographic regions with different ethnicities including Anyang in north China, Shantou in south China, Xinjiang in west China, and the United States. The HPV L1 fragment was detected using SPF1/GP6+ primers. HPV genotyping was performed using genotype specific PCR. Results Two hundred and forty four of 435 samples (56.1%) tested positive for HPV L1. Significant differences in detection rate were observed neither among the three areas of China nor between China and the US. HPV6, 16, 18, 26, 45, 56, 57, and 58 were identified in L1 positive samples. HPV16 and 57 were the most common types in all regions, followed by HPV26 and HPV18. Conclusions HPV infection is common in esophageal carcinoma independent of region and ethnic group of origin. Findings in this study raise the possibility that HPV is involved in esophageal carcinogenesis. Further investigation with a larger sample size over broader geographic areas may be warranted.
Anogenital malignancy has a significant association with high-risk mucosal alpha-human papillomaviruses (alpha-PV), particularly HPV 16 and 18 whereas extragenital SCC has been linked to the presence of cutaneous beta and gamma–HPV types. Vulval skin may be colonised by both mucosal and cutaneous (beta-, mu-, nu- and gamma-) PV types, but there are few systematic studies investigating their presence and their relative contributions to vulval malignancy. Dysregulation of AKT, a serine/threonine kinase, plays a significant role in several cancers. Mucosal HPV types can increase AKT phosphorylation and activity whereas cutaneous HPV types down-regulate AKT1 expression, probably to weaken the cornified envelope to promote viral release. We assessed the presence of mucosal and cutaneous HPV in vulval malignancy and its relationship to AKT1 expression in order to establish the corresponding HPV and AKT1 profile of normal vulval skin, vulval intraepithelial neoplasia (VIN) and vulval squamous cell carcinoma (vSCC). We show that HPV16 is the principle HPV type present in VIN, there were few detectable beta types present and AKT1 loss was not associated with the presence of these cutaneous HPV. We show that HPV16 early gene expression reduced AKT1 expression in transgenic mouse epidermis. AKT1 loss in our VIN cohort correlated with presence of high copy number, episomal HPV16. Maintained AKT1 expression correlated with low copy number, an increased frequency of integration and increased HPV16E7 expression, a finding we replicated in another untyped cohort of vSCC. Since expression of E7 reflects tumour progression, these findings suggest that AKT1 loss associated with episomal HPV16 may have positive prognostic implications in vulval malignancy.
Gibbon, Karen; Byrne, Carolyn R.; Arbeit, Jeffrey M.; Harwood, Catherine A.; O'Shaughnessy, Ryan F. L.
Background The control arm of PATRICIA (PApillomaTRIal against Cancer In young Adults, NCT00122681) was used to investigate the risk of progression from cervical HPV infection to cervical intraepithelial neoplasia (CIN) or clearance of infection, and associated determinants. Methods and Findings Women aged 15-25 years were enrolled. A 6-month persistent HPV infection (6MPI) was defined as detection of the same HPV type at two consecutive evaluations over 6 months and clearance as ?2 type-specific HPV negative samples taken at two consecutive intervals of approximately 6 months following a positive sample. The primary endpoint was CIN grade 2 or greater (CIN2+) associated with the same HPV type as a 6MPI. Secondary endpoints were CIN1+/CIN3+ associated with the same HPV type as a 6MPI; CIN1+/CIN2+/CIN3+ associated with an infection of any duration; and clearance of infection. The analyses included 4825 women with 16,785 infections (3363 womenwith 6902 6MPIs). Risk of developing a CIN1+/CIN2+/CIN3+ associated with same HPV type as a 6MPI varied with HPV type and was significantly higher for oncogenic versus non-oncogenic types. Hazard ratios for development of CIN2+ were 10.44 (95% CI: 6.96-15.65), 9.65 (5.97-15.60), 5.68 (3.50-9.21), 5.38 (2.87-10.06) and 3.87 (2.38-6.30) for HPV-16, HPV-33, HPV-31, HPV-45 and HPV-18, respectively. HPV-16 or HPV-33 6MPIs had ~25-fold higher risk for progression to CIN3+. Previous or concomitant HPV infection or CIN1+ associated with a different HPV type increased risk. Of the different oncogenic HPV types, HPV-16 and HPV-31 infections were least likely to clear. Conclusions Cervical infections with oncogenic HPV types increased the risk of CIN2+ and CIN3+. Previous or concomitant infection or CIN1+ also increased the risk. HPV-16 and HPV-33 have by far the highest risk of progression to CIN3+, and HPV-16 and HPV-31 have the lowest chance of clearance.
Jaisamrarn, Unnop; Castellsague, Xavier; Garland, Suzanne M.; Naud, Paulo; Palmroth, Johanna; Del Rosario-Raymundo, Maria Rowena; Wheeler, Cosette M.; Salmeron, Jorge; Chow, Song-Nan; Apter, Dan; Teixeira, Julio C.; Skinner, S. Rachel; Hedrick, James; Szarewski, Anne; Romanowski, Barbara; Aoki, Fred Y.; Schwarz, Tino F.; Poppe, Willy A. J.; Bosch, F. Xavier; de Carvalho, Newton S.; Germar, Maria Julieta; Peters, Klaus; Paavonen, Jorma; Bozonnat, Marie-Cecile; Descamps, Dominique; Struyf, Frank; Dubin, Gary O.; Rosillon, Dominique; Baril, Laurence
Introdução: atualmente, a infecção genital pelo papilomavírus humano (HPV) constitui-se na DST mais prevalente nos diferentes grupos etários e na maior parte das unidades de saúde públicas. Normalmente é a DST que mais se associa a outras infecções genitais. Objetivos: observar difer- entes formas terapêuticas de pacientes apresentando condiloma acuminado. Observar a ocorrência de associação com sífilis. Métodos: foram estuda-
Tomaz B Isolan; Gutemberg L Almeida Filho; Mauro RL Passos; Renato S Bravo
Epidermodysplasia verruciformis (EV) is a rare disease, characterized by cutaneous warts and associated with a strong predisposition to beta-genus human papillomavirus (HPV). Earlier studies reported high copy numbers of HPV-DNA in nearly all skin tumors from EV patients, but neither HPV replication status in non-lesional skin nor anti-HPV seroreactivity in these patients have been reported yet. We therefore performed a comprehensive viral load analysis for the more common beta-HPV types on skin samples and plucked eyebrow hairs from four EV patients treated at our dermatology department. The results clearly demonstrate that they carry a multiplicity (up to eighteen types) of beta-HPV genotypes in both skin sites. Worthy of note, a high intrapatient concordance for specific types between hair bulbs and skin biopsies was observed and the same beta-PV profile was maintained over time. Viral load analysis revealed a load range between less than one HPV-DNA copy per 100 cells to more than 400 HPV-DNA copies per cell in both eyebrow hairs and skin proliferative lesions. Evaluation of seroreactivity to beta-HPV types in the four EV patients revealed that antibodies against the 16 beta-HPV were significantly more prevalent and showed higher titers than in the controls. PMID:18923444
Dell'Oste, Valentina; Azzimonti, Barbara; De Andrea, Marco; Mondini, Michele; Zavattaro, Elisa; Leigheb, Giorgio; Weissenborn, Sönke J; Pfister, Herbert; Michael, Kristina M; Waterboer, Tim; Pawlita, Michael; Amantea, Ada; Landolfo, Santo; Gariglio, Marisa
Background Human papillomaviruses (HPVs) are the primary etiological agents of cervical cancer and are also involved in the development of other tumours (skin, head and neck). Serological survey of the HPV infections is important to better elucidate their natural history and to disclose antigen determinants useful for vaccine development. At present, the analysis of the HPV-specific antibodies has not diagnostic value for the viral infections, and new approaches are needed to correlate the antibody response to the disease outcome. The aim of this study is to develop a novel ELISA, based on five denatured recombinant HPV16 proteins, to be used for detection HPV-specific antibodies. Methods The HPV16 L1, L2, E4, E6 and E7 genes were cloned in a prokaryotic expression vector and expressed as histidine-tagged proteins. These proteins, in a denatured form, were used in ELISA as coating antigens. Human sera were collected from women with abnormal PAP smear enrolled during an ongoing multicenter HPV-PathogenISS study in Italy, assessing the HPV-related pathogenetic mechanisms of progression of cervical cancer precursor lesions. Negative human sera were collected from patients affected by other infectious agents. All the HPV-positive sera were also subjected to an avidity test to assess the binding strength in the antigen-antibody complexes. Results Most of the sera showed a positive reactivity to the denatured HPV16 proteins: 82% of the sera from HPV16 infected women and 89% of the sera from women infected by other HPV genotypes recognised at least one of the HPV16 proteins. The percentages of samples showing reactivity to L1, L2 and E7 were similar, but only a few serum samples reacted to E6 and E4. Most sera bound the antigens with medium and high avidity index, suggesting specific antigen-antibody reactions. Conclusion This novel ELISA, based on multiple denatured HPV16 antigens, is able to detect antibodies in women infected by HPV16 and it is not genotype-specific, as it detects antibodies also in women infected by other genital HPVs. The assay is easy to perform and has low cost, making it suitable for monitoring the natural history of HPV infections as well as for detecting pre-existing HPV antibodies in women who receive VLP-based HPV vaccination.
Di Bonito, Paola; Grasso, Felicia; Mochi, Stefania; Accardi, Luisa; Dona, Maria Gabriella; Branca, Margherita; Costa, Silvano; Mariani, Luciano; Agarossi, Alberto; Ciotti, Marco; Syrjanen, Kari; Giorgi, Colomba
A human papillomavirus (HPV) vaccine consisting of virus-like particles (VLPs) was recently approved for human use. It is generally assumed that VLP vaccines protect by inducing type-specific neutralizing antibodies. Preclinical animal models cannot be used to test for protection against HPV infections due to species restriction. We developed a model using chimeric HPV capsid\\/cottontail rabbit papillomavirus (CRPV) genome particles to
Andres F. Mejia; Timothy D. Culp; Nancy M. Cladel; Karla K. Balogh; Lynn R. Budgeon; Christopher B. Buck; Neil D. Christensen
The DNA genome of a novel HPV genotype, HPV-125, isolated from a hand wart of an immuno-competent 19-year old male was fully cloned, sequenced and characterized. The full genome of HPV-125 is 7,809-bp in length with a GC content of 46.4%. By comparing the nucleotide sequence of the complete L1 gene, HPV-125 is phylogenetically placed within cutaneotrophic species 2 of Alphapapillomaviruses, and is most closely related to HPV-3 and HPV-28. HPV-125 has a typical genomic organization of Alphapapillomaviruses and contains genes coding for five early proteins, E6, E7, E1, E2 and E4 and two late capsid proteins, L1 and L2. The genome contains two non-coding regions: the first located between the L1 and E6 genes (nucleotide positions 7,137–7,809, length 673-bp) and the second between genes E2 and L2 (nucleotide positions 3,757–4,216, length 460-bp). The E6 protein of HPV-125 contains two regular zinc-binding domains at amino acid positions 29 and 102, whereas the E7 protein exhibits one such domain at position 50. HPV-125 lacks the regular pRb-binding core sequence within its E7 protein. In order to assess the tissue predilection and clinical significance of HPV-125, a quantitative type-specific real-time PCR was developed. The 95% limit-of-detection of the assay was 2.5 copies per reaction (range 1.7–5.7) and the intra- and inter-assay coefficients of variation were 0.47 and 2.00 for 100 copies per reaction, and 1.15 and 2.15 for 10 copies per reaction, respectively. Testing of a representative collection of HPV-associated mucosal and cutaneous benign and malignant neoplasms and hair follicles (a total of 601 samples) showed that HPV-125 is a relatively rare HPV genotype, with cutaneous tropism etiologically linked with sporadic cases of common warts.
Kovanda, Anja; Kocjan, Bostjan J.; Potocnik, Marko; Poljak, Mario
Recent intervention of nonspecific genital ulcers has added refreshing dimensions to genital ulcer disease. It was considered pertinent to dwell on diverse clinical presentation and diagnostic strategies. It seems to possess spectrum. It includes infective causes, Epstein Bar Virus, tuberculosis, Leishmaniasis, HIV/AIDS related ulcers and amoebiasis. Noninfective causes are immunobullous disorders, aphthosis, Behcet's disease (BD), inflammatory bowel disease, lichen planus and lichen sclerosis et atrophicus, drug reactions, premalignant and malignant conditions, pyoderma gangrenosum, and hidradenitis suppurativa. The diagnostic features and treatment option of each disorder are succinctly outlined for ready reference. PMID:24559562
Sehgal, Virendra N; Pandhi, Deepika; Khurana, Ananta
Genitalia are conspicuously variable, even in closely related taxa that are otherwise morphologically very similar. Explaining genital diversity is a longstanding problem that is attracting renewed interest from evolutionary biologists. New studies provide ever more compelling evidence that sexual selection is important in driving genital divergence. Importantly, several studies now link variation in genital morphology directly to male fertilization success,
David J. Hosken; Paula Stockley
Warts from immunosuppressed organ transplant recipients (OTR) persist over years and may progress into non-melanoma skin cancer. Human papillomaviruses (HPV) are considered the causal agents for the development of such warts. We isolated the novel type HPV-117 from a persisting wart by rolling circle amplification. One hundred eighteen warts from immunocompetent patients (IC) and 49 warts from OTR were analyzed by HPV-117 E6 type-specific PCR. As inferred from a phylogenetic analysis, the new type HPV-117 belonged to alpha-PV species 2, including the most similar types HPV-10 and HPV-94. The general prevalence of HPV-117 in warts was 2% in IC (2/118), and 12% in OTR (6/49). The high viral load in dysplastic cells of a Verruca vulgaris was shown by in situ hybridization. Our results suggest an active role of the novel type in the development of cutaneous warts of OTR. PMID:20096912
Köhler, Anja; Gottschling, Marc; Förster, Jana; Röwert-Huber, Joachim; Stockfleth, Eggert; Nindl, Ingo
The activity of the E6/E7 promoter of genital human papillomaviruses (HPVs) is positively and negatively modulated by a complex interplay between a variety of cellular transcription factors and the virally encoded E2 protein. The long control region of genital HPVs contains four E2 binding sites in conserved positions, two of which are very close to the TATA box. Binding of E2 to these two sites has been shown to repress the promoter. To carefully analyze the effect of E2 on the activity of the early promoter P105 of HPV18, we used an in vitro transcription system, which allowed titration of the amount of E2 protein. We found that low amounts of HPV18 E2 stimulated the promoter, whereas increasing amounts resulted in promoter repression. When the affinity was analyzed, it became obvious that E2 bound with highest affinity to E2 binding site 4 (BS-4), located 500 bp upstream of the promoter. The promoter most proximal binding site (BS-1) was the weakest site. Transient transfection assays confirmed that small amounts of HPV type (HPV18) E2 and also of bovine papillomavirus type 1 (BPV1) E2 were able to activate the P105, which was dependent on an intact BS-4. The positive role of BS-4 was also obvious at higher E2 concentrations, since mutation of BS-4 enhanced repression. In contrast to HPV18 E2, BPV1 E2 bound better to BS-1 and, in correlation, was able to more strongly repress the P105 in vivo. Our results suggest a dose-dependent regulation of the HPV18 E6/E7 promoter by E2 due to variable occupancy of its binding sites, which have antagonizing effects on the activity of the E6/E7 promoter.
Steger, G; Corbach, S
... to... Añadir en... Favorites Delicious Digg Google Bookmarks Human papillomavirus (HPV) and Oropharyngeal Cancer - Fact Sheet Human papillomavirus (HPV) can cause serious health problems, including ...
Female genital mutilation, also misleadingly known as female circumcision, is usually performed on girls ranging in from 1 week to puberty. Immediate physical complications include severe pain, shock, infection, bleeding, acute urinary infection, tetanus, and death. Longterm problems include chronic pain, difficulties with micturition and menstruation, pelvic infection leading to infertility, and prolonged and obstructed labor during childbirth. An estimated 80 million girls and women have undergone female genital mutilation. In Britain alone an estimated 10,000 girls are currently at risk. Religious, cultural, medical, and moral grounds rationalize the custom which is practiced primarily in sub-Saharan Africa, the Arab world, Malaysia, Indonesia, and among migrant populations in Western countries. According to WHO it is correlated with poverty, illiteracy, and the low status of women. Women who escape mutilation are not sought in marriage. WHO, the UN Population Fund, the UN Children's Fund, the International Planned Parenthood Federation, and the UN Convention on the Rights of the Child have issued declarations on the eradication of female genital mutilation. In Britain, local authorities have intervened to prevent parents from mutilating their daughters. In 1984, the Inter-African Committee Against Harmful Traditional Practices Affecting Women and Children was established to work toward eliminating female genital mutilation and other damaging customs. National committees in 26 African countries coordinate projects run by local people using theater, dance, music, and storytelling for communication. In Australia, Canada, Europe, and the US women have organized to prevent the practice among vulnerable migrants and refugees. PMID:8400925
Ladjali, M; Rattray, T W; Walder, R J
Background.?There is little information on multiple human papillomavirus (HPV) infections and the potential for type competition in men, yet competition may impact the type-specific efficacy of HPV vaccination. Methods.?Among 2702 uncircumcised men in Kisumu, Kenya, who were seronegative for human immunodeficiency virus, the observed numbers of HPV types detected were compared with the expected number, which was simulated under the assumption of independent infections. To assess the potential for HPV type competition, adjusted odds ratios for pairwise combinations of prevalent HPV type infections were estimated using semi-Bayesian methods. Results.?Half of all men were HPV positive, of whom 57% had multiple HPV types. We observed men without HPV infection and with ?4 HPV types more often than expected if infections were independent. No negative associations between individual HPV types were observed. HPV types 31, 39, 56, 58, and 59 were positively associated with both carcinogenic vaccine types HPV-16 and HPV-18 (2-sided P value <.05). Conclusions.?Men who were HPV infected were likely to test positive for >1 HPV type. Cross-sectional associations between individual HPV types were positive and did not appear to be type-specific. Thus, we did not identify HPV types that are candidates for potential HPV type competition in men.
Poole, Charles; Hudgens, Michael G.; Agot, Kawango; Nyagaya, Edith; Moses, Stephen; Snijders, Peter J. F.; Meijer, Chris J. L. M.; Bailey, Robert C.; Smith, Jennifer S.
In Africa, establishment of an accurate clinical diagnosis in cases of genital ulcer disease is difficult owing to atypical presentation of ulcerations and mixed infections. This is compounded by the frequent lack of suitable laboratory facilities. In 240 cases of genital ulcer disease among mineworkers in Carletonville, South Africa, this study endeavored to correlate the clinical diagnosis with laboratory findings. Clinical accuracy and positive and negative predictive values were determined for each type of genital ulcer disease encountered. Overall, the accuracy of clinical diagnosis was 68% for single infections, 80% for chancroid, 55% for primary syphilis, 27% for lymphogranuloma venereum (LGV), and 22% for genital herpes. Adequate laboratory facilities are indispensible for the establishment of an accurate etiologic diagnosis of genital ulcer disease and thus the institution of appropriate antimicrobial therapy. PMID:2175951
Dangor, Y; Ballard, R C; da L Exposto, F; Fehler, G; Miller, S D; Koornhof, H J
Background Human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma (HNSCC) represents a distinct clinical and epidemiological condition compared with HPV-negative (HPV-) HNSCC. To test the possible involvement of epigenetic modulation by HPV in HNSCC, we conducted a genome-wide DNA-methylation analysis. Methods Using laser-capture microdissection of 42 formalin-fixed paraffin wax-embedded (FFPE) HNSCCs, we generated DNA-methylation profiles of 18 HPV+ and 14 HPV- samples, using Infinium 450 k BeadArray technology. Methylation data were validated in two sets of independent HPV+/HPV- HNSCC samples (fresh-frozen samples and cell lines) using two independent methods (Infinium 450 k and whole-genome methylated DNA immunoprecipitation sequencing (MeDIP-seq)). For the functional analysis, an HPV- HNSCC cell line was transduced with lentiviral constructs containing the two HPV oncogenes (E6 and E7), and effects on methylation were assayed using the Infinium 450 k technology. Results and discussion Unsupervised clustering over the methylation variable positions (MVPs) with greatest variation showed that samples segregated in accordance with HPV status, but also that HPV+ tumors are heterogeneous. MVPs were significantly enriched at transcriptional start sites, leading to the identification of a candidate CpG island methylator phenotype in a sub-group of the HPV+ tumors. Supervised analysis identified a strong preponderance (87%) of MVPs towards hypermethylation in HPV+ HNSCC. Meta-analysis of our HNSCC and publicly available methylation data in cervical and lung cancers confirmed the observed DNA-methylation signature to be HPV-specific and tissue-independent. Grouping of MVPs into functionally more significant differentially methylated regions identified 43 hypermethylated promoter DMRs, including for three cadherins of the Polycomb group target genes. Integration with independent expression data showed strong negative correlation, especially for the cadherin gene-family members. Combinatorial ectopic expression of the two HPV oncogenes (E6 and E7) in an HPV- HNSCC cell line partially phenocopied the hypermethylation signature seen in HPV+ HNSCC tumors, and established E6 as the main viral effector gene. Conclusions Our data establish that archival FFPE tissue is very suitable for this type of methylome analysis, and suggest that HPV modulates the HNSCC epigenome through hypermethylation of Polycomb repressive complex 2 target genes such as cadherins, which are implicated in tumor progression and metastasis.
Genital HPV genotypes are generally distinct serotypes, but whether variants within a genotype can represent serologic subtypes is unclear. In this study we used serum from human volunteers vaccinated with HPV16 L1 VLPs from variant 114K, to examine cross-neutralization of variants from each of the five major phylogenetic branches of HPV16. Recombinant Semliki Forest virus-derived pseudovirions for each variant were generated and combined with serum from vaccines, and the mixture was monitored for infectivity in a standard C127 cell focal transformation assay. Sera from all 10 VLP-immunized individuals had neutralizing activity against each of the variant pseudovirions. For each of the sera, variant titers differed by only fourfold or less from the median titer. Therefore, from a vaccine perspective, HPV16 variants belong to a single serotype. Vaccination with HPV16 114K L1 VLPs generates antibodies that should confer a similar degree of protection against all known phylogenetic branches of HPV16. PMID:11145917
Pastrana, D V; Vass, W C; Lowy, D R; Schiller, J T
Introduction Persistent infections with human papillomavirus (HPV) are a necessary cause of cervical cancer and are responsible for important morbidity in men and women. Since 2007, HPV vaccination has been recommended and funded for all girls aged 12 to 17 in Germany. A previously published cost-effectiveness analysis, using a static model, showed that a quadrivalent HPV vaccination programme for 12-year-old girls in Germany would be cost effective. Here we present the results from a dynamic transmission model that can be used to evaluate the impact and cost-effectiveness of different vaccination schemas. Methods We adapted a HPV dynamic transmission model, which has been used in other countries, to the German context. The model was used to compare a cervical cancer screening only strategy with a strategy of combining vaccination of females aged 12–17 years old and cervical cancer screening, based on the current recommendations in Germany. In addition, the impact of increasing vaccination coverage in this cohort of females aged 12–17 years old was evaluated in sensitivity analysis. Results The results from this analysis show that the current quadrivalent HPV vaccination programme of females ages 12 to 17 in Germany is cost-effective with an ICER of 5,525€/QALY (quality adjusted life year). The incremental cost-effectiveness ratio (ICER) increased to 10,293€/QALY when the vaccine effects on HPV6/11 diseases were excluded. At steady state, the model predicted that vaccinating girls aged 12 to 17 could reduce the number of HPV 6/11/16/18-related cervical cancers by 65% and genital warts among women and men by 70% and 48%, respectively. The impact on HPV-related disease incidence and costs avoided would occur relatively soon after initiating the vaccine programme, with much of the early impact being due to the prevention of HPV6/11-related genital warts. Conclusions These results show that the current quadrivalent HPV vaccination and cervical cancer screening programmes in Germany will substantially reduce the incidence of cervical cancer, cervical intraepithelial neoplasia (CIN) and genital warts. The evaluated vaccination strategies were all found to be cost-effective. Future analyses should include more HPV-related diseases.
High-risk ? mucosal types of human papillomavirus (HPV) cause anogenital and oropharyngeal cancers, whereas ? cutaneous HPV types (e.g. HPV8) have been implicated in non-melanoma skin cancer. Although antibodies against the capsid protein L1 of HPV are considered as markers of cumulative exposure, not all infected persons seroconvert. To identify common genetic variants that influence HPV seroconversion, we performed a two-stage genome-wide association study. Genome-wide genotyping of 316 015 single nucleotide polymorphisms was carried out using the Illumina HumanHap300 BeadChip in 4811 subjects from a central European case-control study of lung, head and neck and kidney cancer that had serology data available on 13 HPV types. Only one association met genome-wide significance criteria, namely that between HPV8 seropositivity and rs9357152 [odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.24-1.50 for the minor allele G; P=1.2 × 10(-10)], a common genetic variant (minor allele frequency=0.33) located within the major histocompatibility complex (MHC) II region at 6p21.32. This association was subsequently replicated in an independent set of 2344 subjects from a Latin American case-control study of head and neck cancer (OR=1.35, 95% CI=1.18-1.56, P=2.2 × 10(-5)), yielding P=1.3 × 10(-14) in the combined analysis (P-heterogeneity=0.87). No heterogeneity was noted by cancer status (controls/lung cancer cases/head and neck cancer cases/kidney cancer cases). This study provides a proof of principle that genetic variation plays a role in antibody reactivity to HPV infection. PMID:21896673
Chen, Dan; McKay, James D; Clifford, Gary; Gaborieau, Valérie; Chabrier, Amélie; Waterboer, Tim; Zaridze, David; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Bencko, Vladimir; Janout, Vladimir; Foretova, Lenka; Mates, Ioan Nicolae; Szeszenia-Dabrowska, Neonila; Curado, Maria Paula; Koifman, Sergio; Menezes, Ana; Wünsch-Filho, Victor; Eluf-Neto, José; Fernández Garrote, Leticia; Matos, Elena; Zelenika, Diana; Boland, Anne; Boffetta, Paolo; Pawlita, Michael; Lathrop, Mark; Brennan, Paul
Objectives The extent to which highly active antiretroviral therapy (HAART) affects HPV acquisition and clearance in HIV-infected women is not well-understood. We sought to describe high risk HPV detection and clearance rates over time since HAART initiation, based on time-varying HIV viral load (VL) and CD4+ T-cell count (CD4) using novel statistical methods. Methods We conducted retrospective analysis of data from completed AIDS Clinical Trials Group (ACTG) A5029 study using multi-state Markov models. Two sets of high risk HPV types from 2003 and 2009 publications were considered. Results There was some evidence that VL>400 copies/mL was marginally associated with higher rate of HPV detection (p=0.068, hazard ratio [HR]=4.67), using the older set of high risk HPV types. Such association was not identified using the latest set of HPV types (p=0.343, HR=2.64). CD4>350 cells/mm3 was significantly associated with more rapid HPV clearance with both sets of HPV types (p=0.001, HR=3.93; p=0.018, HR=2.65). There was no evidence that HPV affects VL or CD4 in all analyses. Conclusions High risk HPV types vary in studies, and they can affect analysis results. Use of HAART to improve CD4 may have an impact in the control of HPV infection, and the decrease in VL to a lesser degree.
KANG, Minhee; CU-UVIN, Susan
The aim of the present study was to investigate the association between HPV-DNA and micronucleus (MN) frequency in women with normal cervical cytology. A total of 158 normal cervical smears were analyzed cytologically. The HPV genome was amplified using the GP5+/bioGP6+ consensus primers. HPV-DNA of high-risk types 16, 18, 31, 33, 39, 45 and 59 were also investigated. Of the 158 samples, 20 (12.7%) and 47 (29.7%) were positive for HPV-DNA and MN, respectively. Evidence for MN was found in 11 out of 20 (55%) HPV-DNA positive samples and in 36 out of 138 (26.1%) HPV-DNA negative ones. MN presence was significantly higher in HPV-DNA positive samples (p = 0.016). On the other hand, the absence of MN observed in a considerable number of HPV-DNA negative samples (102) may be of great value in predicting the absence of HPV. The mean age of HPV-DNA positive women (34.2 ± 12.6) was significantly lower than the mean age of HPV-DNA negative women (43.9 ± 13.7) (p = 0.003). Infection by one or multiple HPV types was found in 11 out of 20 (55.0%) and 9 out of 20 (45.0%) samples, respectively. The evaluation of MN using cervical smears collected for cytology tests could, thus, be used as additional information to monitor a population’s exposure to HPV.
Cassel, Ana Paula Rebelo; Barcellos, Regina Bones; da Silva, Claudia Maria Dornelles; de Matos Almeida, Sabrina Esteves; Rossetti, Maria Lucia Rosa
We conducted a literature review of patients' conditions described under persistent genital arousal disorder and restless genital syndrome, vulvodynia and male genital skin pain of unknown aetiology (penoscrotodynia). Our aim is to improve the understanding of the condition, unify nomenclature and promote evidence-based practice. The most prominent symptom in persistent genital arousal disorder and restless genital syndrome is a spontaneous, unwelcomed, intrusive and distressing vulval sensation. There are similarities between the clinical presentation of vulvodynia, penoscrotodynia, persistent genital arousal disorder and restless genital syndrome patients. The aetiology of persistent genital arousal disorder and restless genital syndrome, similar to vulvodynia, could be better explained in terms of neuro-vascular dysfunction, genital peripheral neuropathy and/or dysfunctional micro-vascular arterio-venous shunting. Erythromelalgia lends itself to explain some cases of restless genital syndrome, who have concurrent restless legs syndrome; and therefore draw parallels with the red scrotum syndrome. The published literature supports the concept of classifying restless genital syndrome as a sub-type of vulvodynia rather than sexual dysfunction. PMID:23970620
Markos, A R; Dinsmore, Wallace
Due to the strong relationship between the Human Papillomavirus (HPV) “high-risk” subtypes and cervical cancers, most HPV-related studies have been focusing on the “high-risk” HPV subtypes 16 and 18. However, it has been suggested that the “low-risk” subtypes of HPV, HPV6 and HPV11, are the major cause of recurrent respiratory papillomatosis and genital warts. In addition, HPV 6 and 11 are also associated with otolaryngologic malignancies, carcinoma of the lung, tonsil, larynx and low-grade cervical lesions. Therefore, development of HPV therapeutic vaccines targeting on subtypes 6 and 11 E6 or E7 are in great need. In this report, we describe two novel engineered DNA vaccines that encode HPV 6 and 11 consensus E6/E7 fusion proteins (p6E6E7 and p11E6E7) by utilizing a multi-phase strategy. Briefly, after generating consensus sequences, several modifications were performed to increase the expression of both constructs, including codon/RNA optimization, addition of a Kozak sequence and a highly efficient leader sequence. An endoproteolytic cleavage site was also introduced between E6 and E7 protein for proper protein folding and for better CTL processing. The expressions of both constructs were confirmed by western blot analysis and immunofluorescence assay. Vaccination with these DNA vaccines could elicit robust cellular immune responses. The epitope mapping assay was performed to further characterize the cellular immune responses induced by p6E6E7 and p11E6E7. The HPV 6 and 11 E6 or E7-specific immunodominant and subdominant epitopes were verified, respectively. The intracellular cytokine staining revealed that the magnitude of IFN-? and TNF-? secretion in antigen-specific CD8+ cells was significantly enhanced, indicating that the immune responses elicited by p6E6E7 and p11E6E7 was heavily skewed toward driving CD8+ T cells. Such DNA immunogens are interesting candidates for further studies on HPV 6 and 11-associated diseases.
Shin, Thomas; Pankhong, Panyupa; Yan, Jian; Khan, Amir S.; Sardesai, Niranjan Y.; Weiner, David B.
Human papillomavirus (HPV) genital infection is a sexually transmitted disease that affects a large proportion of college-aged women. In addition to the distressing medical aspects of HPV infection, sometimes including lengthy and painful treatments, symptom recurrence, a lack of a definitive cure, and its potential for malignant transformation, HPV also results in significant emotional and psychosexual sequalae for the patient. Concurrent with the range of negative emotions experienced by the patient is also a knowledge deficit regarding the disease, its prevention, and its management. This combination of factors within the young women afflicted with this disease often precludes them from effective adherence to their treatment and follow-up plan of care, which are both essential elements in managing this chronic condition. Clinicians who are treating patients with HPV infection must address not only the medical aspects of the disease, but the psychosocial needs as well. This case report describes a newly diagnosed young women with HPV infection and discusses the necessary psychosocial and educational interventions that should be provided to all female patients who are diagnosed with HPV infection. Inclusion of these interventions can reduce the emotional stress that occurs with the diagnosis and can augment a patient's coping skills, thereby serving to improve adherence to the treatment plan and promote a greater sense of empowerment and wellness for the patient. PMID:10977973
Linnehan, M J; Groce, N E
The prevalence of human papillomavirus (HPV)-associated head and neck cancers is increasing, but the prevalence of oral HPV infection in the wider community remains unknown. We sought to determine the prevalence of, and identify risk factors for, oral HPV infection in a sample of young, healthy Australians. For this study, we recruited 307 Australian university students (18-35 years). Participants reported anonymously about basic characteristics, sexual behaviour, and alcohol, tobacco and illicit drugs use. We collected oral rinse samples from all participants for HPV testing and typing. Seven of 307 (2.3%) students tested positive for oral HPV infection (3 HPV-18, one each of HPV-16, -67, -69, -90), and six of them were males (p?=?0.008). Compared to HPV negative students, those with oral HPV infection were more likely to have received oral sex from more partners in their lifetime (p?=?0.0004) and in the last year (p?=?0.008). We found no statistically significant associations with alcohol consumption, smoking or numbers of partners for passionate kissing or sexual intercourse. In conclusion, oral HPV infection was associated with male gender and receiving oral sex in our sample of young Australians. PMID:24637512
Antonsson, Annika; Cornford, Michelle; Perry, Susan; Davis, Marcia; Dunne, Michael P; Whiteman, David C
Thirty laryngeal carcinomas from patients without pre-existing laryngeal papillomatosis were examined by PCR for the presence of HPV DNA. The utmost care was taken during sectioning of the tissue blocks and DNA-extraction in order to avoid false positive results. Three pairs of consensus primers were used: MY9\\/MY11, GP5+\\/GP6+ and CPI\\/CPII. HPV was detected in 1\\/30 carcinomas. The HPV type present
Henning Lindeberg; Annelise Krogdahl
These studies were performed to determine the effect of AD-472, an attenuated human herpes simplex virus (HSV) type 2 or HSV-2 glycoprotein D (gD) when combined with an adjuvant, GPI-0100, a semi-synthetic Quillaja Saponin analog in a genital HSV-2 infection in guinea pigs. While animals immunized with either vaccine had reduced clinical disease, GPI-0100 only improved the efficacy of gD and did not affect the efficacy of the live vaccine. Neither vaccine had any therapeutic effect if administered 24 h after viral infection. PMID:18573279
Quenelle, Debra C; Collins, Deborah J; Rice, Terri L; Prichard, Mark N; Marciani, Dante J; Kern, Earl R
Background Infection with high-risk subtypes of human papillomavirus (HPV) is a central factor in the development of cervical neoplasia. Cell-mediated immunity against HPV16 plays an important role in the resolution of HPV infection and in controlling cervical disease progression. Research suggests that stress is associated with cervical disease progression, but few studies have examined the biological mechanisms that may be driving this association. Purpose This study examines whether stress is associated with immune response to HPV16 among women with cervical dysplasia. Methods Seventy-four women presenting for colposcopy completed measures of health behaviors, stressful life events and perceived stress (Perceived Stress Scale). A blood sample was obtained to evaluate proliferative T-cell response to HPV16, and a cervical sample was obtained during gynecologic exam for HPV-typing. Results Over 55% tested positive for one or more HPV subtypes. Women who did not show proliferative responses to HPV (i.e. non-responders) were more likely to be HPV+ compared to women who had a response (i.e. responders). Consistent with study hypotheses, logistic regression revealed that higher levels of perceived stress were associated with a non-response to HPV16, controlling for relevant covariates. Stressful life events were not associated with T-cell response to HPV. Conclusions Higher levels of perceived stress are associated with impaired HPV-specific immune response in women with cervical dysplasia, suggesting a potential mechanism by which stress may influence cervical disease progression.
Fang, Carolyn Y.; Miller, Suzanne M.; Bovbjerg, Dana H.; Bergman, Cynthia; Edelson, Mitchell I.; Rosenblum, Norman G.; Bove, Betsy A.; Godwin, Andrew K.; Campbell, Donald E.; Douglas, Steven D.
Persistent genital arousal disorder is described in a spontaneous, persistent, and uncontrollable genital arousal in women, with or without orgasm or genital engorgement, unrelated to any feelings of sexual desire. This study aimed to argue that application of Botulinum toxin in the periclitoral region in order to block the dorsal nerve of the clitoris might decrease symptoms of persistent genital arousal disorder. The authors presented 2 cases, in which application of Botulinum toxin resulted in improvement of the symptoms of persistent genital arousal disorder. Botulinum toxin type A treatment protocol is seen as a promising application for the persistent genital arousal disorder. However, further controlled studies in large samples are needed. PMID:24168013
Nazik, Hakan; Api, Murat; Aytan, Hakan; Narin, Raziye
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.
Anal human papillomavirus (HPV) infections are common, and the incidence of anal cancer is high in HIV-infected men who have sex with men (MSM). To evaluate the performance of HPV assays in anal samples, we compared the cobas HPV test (cobas) to the Roche Linear Array HPV genotyping assay (LA) and cytology in HIV-infected MSM. Cytology and cobas and LA HPV testing were conducted for 342 subjects. We calculated agreement between the HPV assays and the clinical performance of HPV testing and HPV genotyping alone and in combination with anal cytology. We observed high agreement between cobas and LA, with cobas more likely than LA to show positive results for HPV16, HPV18, and other carcinogenic types. Specimens testing positive in cobas but not in LA were more likely to be positive for other markers of HPV-related disease compared to those testing negative in both assays, suggesting that at least some of these were true positives for HPV. cobas and LA showed high sensitivities but low specificities for the detection of anal intraepithelial neoplasia grade 2/3 (AIN2/3) in this population (100% sensitivity and 26% specificity for cobas versus 98.4% sensitivity and 28.9% specificity for LA). A combination of anal cytology and HPV genotyping provided the highest accuracy for detecting anal precancer. A higher HPV load was associated with a higher risk of AIN2/3 with HPV16 (Ptrend < 0.001), HPV18 (Ptrend = 0.07), and other carcinogenic types (Ptrend < 0.001). We demonstrate that cobas can be used for HPV detection in anal cytology specimens. Additional tests are necessary to identify men at the highest risk of anal cancer among those infected with high-risk HPV. PMID:24899025
Wentzensen, Nicolas; Follansbee, Stephen; Borgonovo, Sylvia; Tokugawa, Diane; Sahasrabuddhe, Vikrant V; Chen, Jie; Lorey, Thomas S; Gage, Julia C; Fetterman, Barbara; Boyle, Sean; Sadorra, Mark; Tang, Scott Dahai; Darragh, Teresa M; Castle, Philip E
Human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is considered to be a distinct clinical entity with better prognosis than the classical tobacco- and alcohol-associated tumors. The increasing incidence of this neoplasia during the last decades highlights the need to better understand the role of HPV in the development of these cancers. Although the proportion of HNSCC attributed to HPV varies considerably according to anatomical site, overall approximately 25% of all HNSCC are HPV-DNA positive, and HPV-16 is by far the most prevalent type. In this review we discuss the existing evidence for a causal association between HPV infection and HNSCC at diverse anatomical head and neck subsites.
Betiol, J.; Villa, L.L.; Sichero, L.
The HPV-16 E6 and E6(?) proteins have been shown previously to be capable of regulating caspase 8 activity. We now show that the capacity of E6 to interact with caspase 8 is common to diverse HPV types, being also seen with HPV-11 E6, HPV-18 E6 and HPV-18 E6(?). Unlike most E6-interacting partners, caspase 8 does not appear to be a major proteasomal target of E6, but instead E6 appears able to stimulate caspase 8 activation, without affecting the overall apoptotic activity. This would appear to be mediated in part by the ability of the HPV E6 oncoproteins to recruit active caspase 8 to the nucleus. PMID:24503077
Manzo-Merino, Joaquin; Massimi, Paola; Lizano, Marcela; Banks, Lawrence
Objective To describe the relationship between acculturation and human papillomavirus (HPV) infection among diverse US Latinas, a group at high risk for cervical cancer. Method Using survey and medical testing data from the 2003–2004 National Health and Nutrition Examination Survey (NHANES), we examined the relationship between acculturation level and HPV infection among diverse Latinas (n=503) and Mexican American women (n=442). Multivariable logistic regression was performed using infection with any type of HPV and with high-risk oncogenic genotypes as outcome variables. Results More acculturated Mexican American women were more likely to be infected with high-risk HPV than less acculturated women. In multivariate analyses, Mexican Americans with higher levels of self-rated English language ability (2.48 OR, 95% CI: 1.42–4.33); with birth in the US (2.07 OR, 95% CI: 1.03–4.16); and with US born parents (2.98 OR, 95% CI: 1.45–3.72) were more likely to be infected with high-risk HPV genotypes. Mexican American women with higher levels of acculturation were more likely to test positive for other sexually transmitted infections. Conclusion Higher acculturation levels related to more frequent infection with high-risk HPV genotypes and other STIs among US Mexican American women. This association may in part be due to engagement in sexual behaviors.
Coronado, Gloria; Rodriguez, Hector P.; Thompson, Beti
In 2009, the United States approved quadrivalent HPV vaccine for males 9–26 years old, but data on vaccine uptake are lacking. We determined HPV vaccine uptake among adolescent males, as well as stage of adoption and vaccine acceptability to parents and their sons. A national sample of parents of adolescent males ages 11–17 years (n=547) and their sons (n=421) completed online surveys during August and September 2010. Analyses used multivariate linear regression. Few sons (2%) had received any doses of HPV vaccine, and most parents and sons were unaware the vaccine can be given to males. Parents with unvaccinated sons were moderately willing to get their sons free HPV vaccine (mean=3.37, SD=1.21, possible range 1–5). Parents were more willing to get their sons vaccinated if they perceived higher levels of HPV vaccine effectiveness (?=0.20) or if they anticipated higher regret about their sons not getting vaccinated and later developing an HPV infection (?=0.32). Vaccine acceptability was also modest among unvaccinated sons (mean=2.98, SD=1.13, possible range 1–5). Sons were more willing to get vaccinated if they perceived higher peer acceptance of HPV vaccine (?=0.39) or anticipated higher regret about not getting vaccinated and later developing an HPV infection (?=0.22). HPV vaccine uptake was nearly nonexistent a year after permissive national recommendations were first issued for males. Vaccine acceptability was moderate among both parents and sons. Efforts to increase vaccine uptake among adolescent males should consider the important role of peer acceptance and anticipated regret.
Reiter, Paul L.; McRee, Annie-Laurie; Kadis, Jessica A.; Brewer, Noel T.
Infection with human papilloma virus (HPV) is almost universal and eventually asymptomatic, but pathologic infection with HPV is severe, recurrent, and recalcitrant to therapy. It is also an underappreciated manifestation of primary immunodeficiency. Mutations in EVER1, EVER2, GATA2, CXCR4, and DOCK8 are typically associated with extensive HPV infections, whereas several other primary immune defects have severe HPV much less frequently. We review immunodeficiencies with severe HPV infections and the mechanisms underlying them.
Leiding, Jennifer W.; Holland, Steven M.
Abstract Bacterial vaginosis has been associated with genital HIV-1 shedding; however, the effect of specific vaginal bacterial species has not been assessed. We tested cervicovaginal lavage from HIV-1-seropositive women for common Lactobacillus species: L. crispatus, L. jensenii, and seven BV-associated species: BVAB1, BVAB2, BVAB3, Leptotrichia, Sneathia, Megasphaera, and Atopobium spp. using quantitative PCR. We used linear and Poisson regression to evaluate associations between vaginal bacteria and genital HIV-1 RNA and DNA. Specimens from 54?U.S. (310 visits) and 50 Kenyan women (137 visits) were evaluated. Controlling for plasma viral load, U.S. and Kenyan women had similar rates of HIV-1 RNA (19% of visits vs. 24%; IRR=0.95; 95% CI 0.61, 1.49) and DNA shedding (79% vs. 76%; IRR=0.90; 0.78, 1.05). At visits during antiretroviral therapy (ART), the likelihood of detection of HIV-1 RNA shedding was greater with BVAB3 (IRR=3.16; 95% CI 1.36, 7.32), Leptotrichia, or Sneathia (IRR=2.13; 1.02, 4.72), and less with L. jensenii (IRR=0.39; 0.18, 0.84). At visits without ART, only L. crispatus was associated with a lower likelihood of HIV-1 RNA detection (IRR=0.6; 0.40, 0.91). Vaginal Lactobacillus species were associated with lower risk of genital HIV-1 shedding, while the presence of certain BV-associated species may increase that risk.
Balkus, Jennifer E.; Fredricks, David; Liu, Congzhou; McKernan-Mullin, Jennifer; Frenkel, Lisa M.; Mwachari, Christina; Luque, Amneris; Cohn, Susan E.; Cohen, Craig R.; Coombs, Robert; Hitti, Jane
Background.?Whether unique human immunodeficiency type 1 (HIV) genotypes occur in the genital tract is important for vaccine development and management of drug resistant viruses. Multiple cross-sectional studies suggest HIV is compartmentalized within the female genital tract. We hypothesize that bursts of HIV replication and/or proliferation of infected cells captured in cross-sectional analyses drive compartmentalization but over time genital-specific viral lineages do not form; rather viruses mix between genital tract and blood. Methods.?Eight women with ongoing HIV replication were studied during a period of 1.5 to 4.5 years. Multiple viral sequences were derived by single-genome amplification of the HIV C2-V5 region of env from genital secretions and blood plasma. Maximum likelihood phylogenies were evaluated for compartmentalization using 4 statistical tests. Results.?In cross-sectional analyses compartmentalization of genital from blood viruses was detected in three of eight women by all tests; this was associated with tissue specific clades containing multiple monotypic sequences. In longitudinal analysis, the tissues-specific clades did not persist to form viral lineages. Rather, across women, HIV lineages were comprised of both genital tract and blood sequences. Conclusions.?The observation of genital-specific HIV clades only in cross-sectional analysis and an absence of genital-specific lineages in longitudinal analyses suggest a dynamic interchange of HIV variants between the female genital tract and blood.
Bull, Marta E.; Heath, Laura M.; McKernan-Mullin, Jennifer L.; Kraft, Kelli M.; Acevedo, Luis; Hitti, Jane E.; Cohn, Susan E.; Tapia, Kenneth A.; Holte, Sarah E.; Dragavon, Joan A.; Coombs, Robert W.; Mullins, James I.; Frenkel, Lisa M.
... How is Genital / Vulvovaginal Candidiasis Treated? Several different antifungal medications are available to treat genital candidiasis. Antifungal vaginal suppositories or creams are commonly used. The ...
... 452-9622 Will HPV vaccination be covered by health insurance? Most health insurance plans cover recommended vaccines. But there may be ... American Indian, or Alaska Native or have no health insurance. "Underinsured" children who have health insurance that does ...
Persistent infection with human papillomavirus (HPV) type 16 is a major risk factor for the development of head and neck squamous cell carcinoma (HNSCC), in particular oropharyngeal squamous cell carcinoma (OPSCC). The oropharyngeal epithelium differs from the mucosal epithelium at other commonly HPV16-infected sites (i.e., cervix and anogenital region) in that it is juxtaposed with the underlying lymphatic tissue, serving a key immunologic function in the surveillance of inhaled and ingested pathogens. Therefore, the natural history of infection and immune response to HPV at this site may differ from that at other anatomic locations. This review summarizes the literature concerning the adaptive immune response against HPV in the context of HNSCC, with a focus on the T-cell response. Recent studies have shown that a broad repertoire of tumor-infiltrating HPV-specific T-cells are found in nearly all patients with HPV-positive tumors. A systemic response is found in only a proportion of these. Furthermore, the local response is more frequent in OPSCC patients than in cervical cancer patients and HPV-negative OPSCC patients. Despite this, tumor persistence may be facilitated by abnormalities in antigen processing, a skewed T-helper cell response, and an increased local prevalence of T-regulatory cells. Nonetheless, the immunologic profile of HPV-positive vs. HPV-negative HNSCC is associated with a significantly better outcome, and the HPV-specific immune response is suggested to play a role in the significantly better response to therapy of HPV-positive patients. Immunoprofiling may prove a valuable prognostic tool, and immunotherapy trials targeting HPV are underway, providing hope for decreasing treatment-related toxicity. PMID:23913554
Andersen, Anne Skou; Koldjaer Sølling, Anne Sophie; Ovesen, Therese; Rusan, Maria
Persistent HPV infection plays a major role in cervical cancer. This study was undertaken to identify HPV types in a cohort of Indian women with locally advanced cervical cancer as well as to determine the physical state and/or site of viral integration in the host genome. Pretreatment biopsies (n?=?270) from patients were screened for HPV infection by a high throughput HPV genotyping assay based on luminex xMAP technology as well as MY09/11 PCR and SPF1/2 PCR. Overall HPV positivity was observed to be 95%, with HPV16 being most common (63%) followed by infection with HPV18. Integration status of the virus was identified using Amplification of Papillomavirus Oncogene Transcripts (APOT) assay in a subset of samples positive for HPV16 and/or HPV18 (n?=?86) and with an adequate follow-up. The data was correlated with clinical outcome of the patients. Integration of the viral genome was observed in 79% of the cases and a preference for integration into the chromosomal loci 1p, 3q, 6q, 11q, 13q and 20q was seen. Clinical data revealed that the physical state of the virus (integrated or episomal) could be an important prognostic marker for cervical cancer. PMID:22815898
Das, Poulami; Thomas, Asha; Mahantshetty, Umesh; Shrivastava, Shyam K; Deodhar, Kedar; Mulherkar, Rita
Purpose. To describe the acquisition, persistence, and clearance of HPV infection in women with CIN 2 followed up for 12 months. Methods. Thirty-seven women with CIN 2 biopsy, who have proven referral to cervical smear showing low-grade squamous intraepithelial lesions or atypical squamous cells of undetermined significance and tested for HPV, were followed up for one year with cervical smear, colposcopy, and HPV test every three months. HPV DNA was detected by the polymerase chain reaction and genotyping by reverse line blot hybridization assay. Results. CIN 2 regression rate was 49% (18/37), persistence as CIN 1 or CIN 2 was 22% (8/37), and progression to CIN 3 was 29% (11/37). Multiple HPV types were observed at admission in 41% (15/37) of cases. HPV 16 was detected at admission in 58% (11/19) of the cases that persisted/progressed and in 39% (7/18) of the cases that regressed. HPV 16 was considered possibly causal in 67% (10/15) of the cases that persisted or progressed and in 10% (1/10) of the cases that regressed (P = 0.01). Conclusion. Multiple HPV infections were frequently detected among women with CIN 2 at admission and during the followup. The CIN 2 associated with HPV 16 was more likely to persist or to progress to CIN 3. PMID:24369469
Loffredo D'Ottaviano, Maria Gabriela; Discacciati, Michelle Garcia; Andreoli, Maria Antonieta; Costa, Maria Cecília; Termini, Lara; Rabelo-Santos, Silvia H; Villa, Luisa Lina; Zeferino, Luiz Carlos
Purpose. To describe the acquisition, persistence, and clearance of HPV infection in women with CIN 2 followed up for 12 months. Methods. Thirty-seven women with CIN 2 biopsy, who have proven referral to cervical smear showing low-grade squamous intraepithelial lesions or atypical squamous cells of undetermined significance and tested for HPV, were followed up for one year with cervical smear, colposcopy, and HPV test every three months. HPV DNA was detected by the polymerase chain reaction and genotyping by reverse line blot hybridization assay. Results. CIN 2 regression rate was 49% (18/37), persistence as CIN 1 or CIN 2 was 22% (8/37), and progression to CIN 3 was 29% (11/37). Multiple HPV types were observed at admission in 41% (15/37) of cases. HPV 16 was detected at admission in 58% (11/19) of the cases that persisted/progressed and in 39% (7/18) of the cases that regressed. HPV 16 was considered possibly causal in 67% (10/15) of the cases that persisted or progressed and in 10% (1/10) of the cases that regressed (P = 0.01). Conclusion. Multiple HPV infections were frequently detected among women with CIN 2 at admission and during the followup. The CIN 2 associated with HPV 16 was more likely to persist or to progress to CIN 3.
Loffredo D'Ottaviano, Maria Gabriela; Andreoli, Maria Antonieta; Costa, Maria Cecilia; Rabelo-Santos, Silvia H.; Villa, Luisa Lina; Zeferino, Luiz Carlos
At least 12,000 women are diagnosed with cervical cancer each year in the United States, accounting for at least 4,000 deaths. Worldwide, cervical cancer is the second most common type of cancer among women. The human papilloma virus (HPV) has been linked to at least 70% of all cervical cancer. HPV can be divided into 2 categories: (a) low risk,…
Objective.In this study, we investigated the presence of high-risk (HR) HPV types most prevalent in the Hungarian population in surgically removed cervical cancers and pelvic lymph nodes. The aim of our work was to determine the prognostic significance of HPV status in the lymph nodes draining the tumor.
Tibor Füle; Zsolt Csapó; Miklós Máthé; Péter Tátrai; Viktória László; Zoltán Papp; Ilona Kovalszky
The primary underlying cause of cervical cancer is infection with one or more high-risk (HR) types of the human papilloma virus (HPV). Detection and typing of HPV have been commonly carried out by PCR-based assays, where HPV detection and typing are two separate procedures. Here, we present a multiplex PCR-based HPV typing assay that detects 20 HPV types (15 HR, 3 probably HR and 2 low risk) using type-specific primers and agarose gel electrophoresis. 46 cervical, urethral, and biopsy samples were analyzed by both Multiplex PCR and PGMY09/11 consensus PCR, and results were compared. 611 samples were further analyzed by Multiplex PCR, 282 were positive for HR HPV, and 101 showed multiple HR HPV infections. The relatively ease and economic accessibility of the method and its improved ability to detect high-risk HPV types in multiple HPV-infected samples make it an attractive option for HPV testing. PMID:23724318
We report a series of 14 patients with 19 self-inflicted genital injuries during a period of 10 years. Of the patients 65% were psychotic and 35% were not psychotic. Repeated attempts at genital self-mutilation occurred in 31% of the cases, mainly in the psychotic group. A history of alcohol and/or drug abuse was present in 55% of the cases. Injuries varied from simple laceration of penile or scrotal skin to actual amputation of the penis or testis. The degree of injury did not differ between the psychotic and nonpsychotic patients. Surgical management and outcome varied according to the severity of the injury, the delay in presentation for treatment, and the degree of alteration in the mental status and behavior. Followup of 9 patients showed good cosmetic results with no immediate or delayed complications related to the injury. The functional results in patients with penile replantation were satisfactory. In 1 patient a urethral stricture developed that was successfully managed endoscopically. Erectile function was difficult to assess because of the marked diversity of sexual behavior in this group. PMID:8371374
Aboseif, S; Gomez, R; McAninch, J W
Background Metaplastic carcinoma, an uncommon subtype of breast cancer, is part of the spectrum of basal-like, triple receptor-negative breast carcinomas. The present study examined 20 surgical specimens of metaplastic breast carcinomas, for the presence of high-risk Human papillomavirus (HPV), which is suspected to be a potential carcinogenic agent for breast carcinoma. Methods Mastectomy specimens from patients harboring metaplastic breast carcinoma, as defined by the World Health Organization (WHO), and who attended the Instituto Nacional de Cancerologia in Mexico City, were retrieved from the files of the Department of Pathology accumulated during a 16-year period (1995–2008). Demographic and clinical information was obtained from patients’ medical records. DNA was extracted from formalin-fixed, paraffin-embedded tumors and HPV type-specific amplification was performed by means of Polymerase chain reaction (PCR). Quantitative Real-time (RT) PCR was conducted in HPV positive cases. Statistically, the association of continuous or categorical variables with HPV status was tested by the Student t, the Chi square, or Fisher’s exact tests, as appropriate. Results High-risk HPV DNA was detected in eight (40%) of 20 metaplastic breast carcinomas: seven (87.5%) HPV-16 and one (12.5%) HPV-18. Mean age of patients with HPV-positive cases was 49 years (range 24–72 years), the same as for HPV-negative cases (range, 30–73 years). There were not striking differences between HPV?+?and HPV– metaplastic carcinomas regarding clinical findings. Nearly all cases were negative for estrogen, progesterone and Human epidermal growth factor receptor 2 (HER2), but positive for Epidermal growth factor receptor (EGFR). Conclusions High-risk HPV has been strongly associated with conventional breast carcinomas, although the subtle mechanism of neoplastic transformation is poorly understood. In Mexican patients, the prevalence of HPV infection among metaplastic breast carcinomas is higher than in non-metaplastic ones, as so the HPV viral loads; notwithstanding, HPV viral loads show wide variation and remain even lower than cervical and other non-cervical carcinomas, making it difficult to assume that HPV could play a key role in breast carcinogenesis. Further studies are warranted to elucidate the meaning of the presence of high-risk HPVDNA in breast carcinomas.
Background Vaccines, that target human papillomavirus (HPV) high risk genotypes 16 and 18, have recently been developed. This study was aimed at determining genotypes commonly found in high-risk and multiple-HPV infections in Jamaican women. Two hundred and fifty three (253) women were enrolled in the study. Of these, 120 pregnant women, aged 15–44 years, were recruited from the Ante Natal Clinic at the University Hospital of the West Indies and 116 non-pregnant, aged 19–83, from a family practice in Western Jamaica. Cervical cell samples were collected from the women and HPV DNA was detected using Polymerase Chain Reaction and Reverse Line Hybridization. HPV genotypes were assessed in 236 women. Data were collected from January 2003 to October 2006. Results HPV DNA was detected in 87.7% (207/236) and of these 80.2% were positive for high-risk types. The most common high-risk HPV types were: HPV 45 (21.7%), HPV 58 (18.8%), HPV 16 (18.4%), HPV 35 (15.0%), HPV 18 (14.5%), HPV 52 (12.0%) and HPV 51(11.1%). Other high-risk types were present in frequencies of 1.4% – 7.2%. Multivariate regression analyses showed that bacterial vaginosis predicted the presence of multiple infections (OR 3.51; CI, 1.26–9.82) and that alcohol use (OR 0.31; CI, 0.15–0.85) and age at first sexual encounter (12–15 years: OR 3.56; CI, 1.41–9.12; 16–19 years, OR 3.53, CI, 1.22–10.23) were significantly associated with high risk infections. Cervical cytology was normal in the majority of women despite the presence of high-risk and multiple infections. Conclusion HPV genotype distribution in this group of Jamaican women differs from the patterns found in Europe, North America and some parts of Asia. It may be necessary therefore to consider development of other vaccines which target genotypes found in our and similar populations. HPV genotyping as well as Pap smears should be considered.
Watt, Angela; Garwood, David; Jackson, Maria; Younger, Novie; Ragin, Camille; Smikle, Monica; Fletcher, Horace; McFarlane-Anderson, Norma
The prevalence of chlamydial genital infection was studied in 177 prostitutes in Iran; 100 in Teheran and 77 in the port of Bandar Abbas. Chlamydia trachomatis was isolated in eight (6.9%) of 116 patients with valid cultures. Type-specific antibodies were found against C trachomatis serotypes D to K (genital serotypes) in 94.2% and against serotypes A to C (trachoma serotypes) in 2% of the prostitutes. Type-specific IgM at a titre of greater than or equal to 8, indicating current infection, was found in 29.2%, whereas type-specific IgG at a titre greater than or equal to 64, suggesting a current or recent infection, was present in 71.5%. The lower chlamydial isolation rate in these women may have been due to previous treatment with antichlamydial drugs and because of immune responses resulting from repeated reinfection with chlamydiae. The results indicate that in Iran prostitutes are commonly infected with C trachomatis and are probably a major reservoir of chlamydial genital infection. PMID:6824908
Darougar, S; Aramesh, B; Gibson, J A; Treharne, J D; Jones, B R
The aim of the present study was to investigate the cytotoxicity of natural killer (NK) cells to CaSki cells following knockdown of the E7 protein of the human papillomavirus type 16 (HPV16E7). Recombinant adenovirus-short hairpin-E7 protein of the human panillomavirus type 16 (Ad?sh?HPV16E7) was constructed and used to infect CaSki cells. The expression of HPV16E7 in CaSki cells was assessed using western blot analysis. The expression of cell surface molecule major histocompatibility complex?I (MHC?I) in CaSki cells infected with Ad?sh?HPV16E7 was examined using flow cytometry. The cytotoxicity of NK cells isolated and expanded from healthy volunteers on Ad?sh?HPV16E7?infected CaSki cells was assessed using the lactate dehydrogenase (LDH) release assay. Ad?sh?HPV16E7 was successfully constructed and able to inhibit HPV16E7 the expression in CaSki cells. The expression of major histocompa-tibility complex I (MHC?I), a surface molecule, in CaSki cells was increased after infection with Ad?sh?HPV16E7. Compared with the controls, the cytotoxicity of NK cells on CaSki cells, which were infected with Ad?sh?HPV16E7, was decreased (p<0.05). In conclusion, HPV16E7 suppresses the expression of MHC?I on CaSki cells to evade cytotoxic T?cell (CTL) response. However, it was possible to enhance the cytotoxicity of expanded NK cells to cervical cancer cells or HPV16?infected cells in vitro, indicating that NK cells may be used for immunotherapy of cervical cancer. PMID:24566606
Guo, Huimin; Hu, Ruili; Guan, Xinlei; Guo, Fang; Zhao, Shuzhen; Zhang, Xueying
Background Increasingly, countries have introduced female vaccination against human papillomavirus (HPV), causally linked to several cancers and genital warts, but few have recommended vaccination of boys. Declining vaccine prices and strong evidence of vaccine impact on reducing HPV-related conditions in both women and men prompt countries to reevaluate whether HPV vaccination of boys is warranted. Methods A previously-published dynamic model of HPV transmission was empirically calibrated to Norway. Reductions in the incidence of HPV, including both direct and indirect benefits, were applied to a natural history model of cervical cancer, and to incidence-based models for other non-cervical HPV-related diseases. We calculated the health outcomes and costs of the different HPV-related conditions under a gender-neutral vaccination program compared to a female-only program. Results Vaccine price had a decisive impact on results. For example, assuming 71% coverage, high vaccine efficacy and a reasonable vaccine tender price of $75 per dose, we found vaccinating both girls and boys fell below a commonly cited cost-effectiveness threshold in Norway ($83,000/quality-adjusted life year (QALY) gained) when including vaccine benefit for all HPV-related diseases. However, at the current market price, including boys would not be considered ‘good value for money.’ For settings with a lower cost-effectiveness threshold ($30,000/QALY), it would not be considered cost-effective to expand the current program to include boys, unless the vaccine price was less than $36/dose. Increasing vaccination coverage to 90% among girls was more effective and less costly than the benefits achieved by vaccinating both genders with 71% coverage. Conclusions At the anticipated tender price, expanding the HPV vaccination program to boys may be cost-effective and may warrant a change in the current female-only vaccination policy in Norway. However, increasing coverage in girls is uniformly more effective and cost-effective than expanding vaccination coverage to boys and should be considered a priority.
Burger, Emily A.; Sy, Stephen; Nygard, Mari; Kristiansen, Ivar S.; Kim, Jane J.
HSV-2 infection is common and generally asymptomatic, but it is associated with increased HIV susceptibility and disease progression. This may relate to herpes-mediated changes in genital and systemic immunology. Cervical cytobrushes and blood were collected from HIV-uninfected African/Caribbean women in Toronto, and immune cell subsets were enumerated blindly by flow cytometry. Immune differences between groups were assessed by univariate analysis and confirmed using a multivariate model. Study participants consisted of 46 women, of whom 54% were infected with HSV-2. T cell activation and expression of the mucosal homing integrin ?4?7 (19.60 versus 8.76%; p < 0.001) were increased in the blood of HSV-2-infected women. Furthermore, expression of ?4?7 on blood T cells correlated with increased numbers of activated (coexpressing CD38/HLA-DR; p = 0.004) and CCR5(+) (p = 0.005) cervical CD4(+) T cells. HSV-2-infected women exhibited an increase in the number of cervical CD4(+) T cells (715 versus 262 cells/cytobrush; p = 0.016), as well as an increase in the number and proportion of cervical CD4(+) T cells that expressed CCR5(+) (406 versus 131 cells, p = 0.001; and 50.70 versus 34.90%, p = 0.004) and were activated (112 versus 13 cells, p < 0.001; and 9.84 versus 4.86%, p = 0.009). Mannose receptor expression also was increased on cervical dendritic cell subsets. In conclusion, asymptomatic HSV-2 infection was associated with significant systemic and genital immune changes, including increased immune activation and systemic ?4?7 expression; correlation of the latter with highly HIV-susceptible CD4(+) T cell subsets in the cervix may provide a mechanism for the increased HIV susceptibility observed in asymptomatic HSV-2-infected women. PMID:24760150
Shannon, Brett; Yi, Tae Joon; Thomas-Pavanel, Jamie; Chieza, Lisungu; Janakiram, Praseedha; Saunders, Megan; Tharao, Wangari; Huibner, Sanja; Remis, Robert; Rebbapragada, Anu; Kaul, Rupert
Objectives: The study evaluated pathognomic histopathological features with the help of light microscopy for detecting the integration of human papillomavirus (HPV) (type 16 and 18) in oral squamous cell carcinoma (OSCC). Materials and Methods: Forty-five histopathologically diagnosed cases of OSCC were evaluated for the presence of E6/E7 protein of HPV (16 + 18) with the help of nested multiplex polymerase chain reaction. Both HPV-positive and -negative cases were evaluated for four histological features: Koilocytes, dyskeratosis, invasion, and alteration of collagen. Results: Fischer's exact test showed significant difference (P < 0.01%) for the presence of koilocytes and dyskeratosis, whereas no difference was observed for invasion and alteration in collagen between HPV-positive and -negative OSCC. Conclusion: The presence of koilocytes and dyskeratosis at light microscopic level can be used as a marker for the presence of HPV (type 16 and 18) in OSCC.
Khangura, Rajbir Kaur; Sengupta, Shamindra; Sircar, Keya; Sharma, Bhudev; Singh, Sanjeet; Rastogi, Varun
Thirty laryngeal carcinomas from patients without pre-existing laryngeal papillomatosis were examined by PCR for the presence of HPV DNA. The utmost care was taken during sectioning of the tissue blocks and DNA-extraction in order to avoid false positive results. Three pairs of consensus primers were used: MY9/MY11, GP5+/GP6+ and CPI/CPII. HPV was detected in 1/30 carcinomas. The HPV type present could not be determined, but it was not type 6, 11, 13, 16, 18, 30, 31, 33, 35 or 45. In other studies the reported frequency of HPV in laryngeal carcinomas, as estimated by PCR, varies between 3-85%. The reasons for this unacceptable variation in reported results are discussed. The present results indicate that HPV DNA does not have a major role in malignant tumours of the larynx in patients without pre-existing recurrent laryngeal papillomatosis. PMID:10656604
Lindeberg, H; Krogdahl, A
Human papillomaviruses (HPVs) are associated with proliferative lesions in a variety of human epithelial types. A 38-year-old female presented with a diagnosis of urethral condyloma acuminatum. She underwent transurethral resection of the urethral condyloma. At that time, multiple (five) bladder tumors were simultaneously found and also removed by transurethral resection. Four of the bladder tumors were diagnosed as squamous papilloma, and the other was urothelial inverted papilloma. Postoperative course was uneventful. Genomic DNA was extracted from 10??m thick sections of each bladder tumor as well as urethral condyloma. Then, 16 types of HPV DNA sequences were assessed with the PapiPlex method using genomic DNA samples extracted from each bladder tumor as well as urethral condyloma. HPV-11 was detected in DNA extracted from the urethral condyloma, while no HPV DNA sequences were positive in any of the genomic DNA samples extracted from the bladder tumors.
Nakazaki, Natsuko; Zaitsu, Masayoshi; Mikami, Koji; Yui, Shunsuke; Kanatani, Ayumi; Nakatani, Takushi; Ito, Akiko; Takeshima, Yuta; Tonooka, Akiko; Oka, Hideaki; Miki, Tomoko; Takeuchi, Takumi
OBJECTIVE: To evaluate the risk of vulvar vestibulitis syndrome (VVS) associated with genital infections in a case-control study. METHODS: Diagnosed cases with VVS (n = 69) and age-frequency-matched healthy controls (n = 65) were enrolled from gynecology clinics in a university medical hospital during 1999. They were compared for potential risk factors and symptoms of disease. RESULTS: VVS cases had a significantly higher risk of physician-reported bacterial vaginosis (BV) (odds ratio, OR = 9.4), Candida albicans (OR = 5.7), pelvic inflammatory disease (PID) (OR = 11.2), trichomoniasis (OR = 20.6), and vulvar dysplasia (OR = l5.7) but no risk associated with human papillomavirus (HPV), ASCUS, cervical dysplasia, genital warts, chlamydia, genital herpes or gonorrhea. Genital symptoms reported significantly more often with VVS included vulvar burning (91 vs. 12%), dyspareunia (81 vs. 15%), vulvar itching (68 vs. 23%) and dysuria (54 vs. 19%) (p < 0.0001). CONCLUSION: A history of genital infections is associated with an increased risk of VVS. Long-term follow-up case-control studies are needed to elucidate etiologic mechanisms, methods for prevention and effective treatment.
Smith, Elaine M; Ritchie, Justine M; Galask, Rudolph; Pugh, Erica E; Jia, Jian; Ricks-McGillan, Joan
Aims: To monitor the association between the course of high risk human papillomavirus (HR-HPV) infection and the development of cervical neoplasia over time, from a baseline of normal cervical cytology. Methods: This paper presents the follow up data from a previous cross sectional analysis. Women from a screening population who had normal cytology and who were HR-HPV positive were recalled after two to three years for cytology and HPV genotyping. The development of cervical neoplasia at follow up was related to the course of HPV infection (clearance, persistence, or sequential infection) and the presence of single or multiple HPV infections at baseline. A comparator control group of women who were HPV and cytologically negative at baseline were selected from the same population. Results: Twelve cases of dyskaryosis were found in women who were HPV positive at baseline; four were high grade. Only three cases of low grade dyskaryosis were found in the control group. Women with type specific persistent infections were significantly more likely to develop cervical neoplasia than women who cleared the infection (p?=?0.0001) or were sequentially infected with different types (p?=?0.001). Women with multiple HPV infections at baseline were no more likely to develop cervical dyskaryosis than those with a single infection. Conclusions: Type specific persistent HR-HPV infection as monitored by genotyping can identify women at increased risk of cervical neoplasia more accurately than a single or repeated presence/absence HPV test. The cost effectiveness of such an approach should be investigated by an appropriate, large scale cost–benefit analysis.
Cuschieri, K S; Cubie, H A; Whitley, M W; Gilkison, G; Arends, M J; Graham, C; McGoogan, E
Genital symptoms in tropical countries and among returned travellers can arise from a variety of bacterial, protozoal, and helminthic infections which are not usually sexually transmitted. The symptoms may mimic classic sexually transmitted infections (STIs) by producing ulceration (for example, amoebiasis, leishmaniasis), wart-like lesions (schistosomiasis), or lesions of the upper genital tract (epididymo-orchitis caused by tuberculosis, leprosy, and brucellosis; salpingitis as a result of tuberculosis, amoebiasis, and schistosomiasis). A variety of other genital symptoms less suggestive of STI are also seen in tropical countries. These include hydrocele (seen with filariasis), which can be no less stigmatising than STI, haemospermia (seen with schistosomiasis), and hypogonadism (which may occur in lepromatous leprosy). This article deals in turn with genital manifestations of filariasis, schistosomiasis, amoebiasis, leishmaniasis, tuberculosis and leprosy and gives clinical presentation, diagnosis, and treatment.
... include hormone treatment or surgery on the genitals. Bladder exstrophy and epispadias. Bladder exstrophy is when the bladder is turned inside out ... defect in the urethra that often happens with bladder exstrophy. It can cause these problems: For boys, a ...
HR-HPV subtypes are strongly linked to etiology of many human cancers including oral cancer. The epidemiology of infection with different HPV genotypes greatly varies in different countries. The aim of this study was to identify and genotype the HR-HPV subtypes in oral tissues obtained from Sudanese patients with oral lesions. In this retrospective study 200 patients with oral lesions were screened by molecular methods (PCR) for the presence of HR-HPV subtypes. Of the 200 patients, 100/200 were patients with oral cancer (ascertained as case group) and 100/200 were patients with non-neoplastic oral lesions (ascertained as control group). Out of the 200 patients, 12/200 (6%) were found with HR-HPV infection. Of the 12 positive patients, 8/12 (66.7%) were among cases and the remaining 4/12 (33.3%) were among control group. The distribution of different genotypes was: type HPV 16 6/12 (50%), HPV18 4/12 (34%), HPV 31 1/12 (8%) and HPV 33 1/12 (8%). In view of these findings, HPV particularly subtypes 16 and 18 play a role in the etiology of oral cancer in the Sudan.
Babiker, Ali Yousif; Eltom, Faris Margani; Abdalaziz, Mohamed S; Rahmani, Arshad; Abusail, Saadalnour; Ahmed, Hussain Gadelkareem
Human papillomavirus (HPV) is a non-enveloped DNA virus with an approx 8000 base pair genome. Infection with certain types of HPV is associated with cervical cancer, although the molecular mechanism by which HPV induces carcinogenesis is poorly understood. Three genes encoded by HPV16 are regarded as oncogenic - E5, E6, and E7. The role of E5 has been controversial. Expression of HPV16 E5 causes cell-cell fusion, an event that can lead to increased chromosomal instability, particularly in the presence of cell cycle checkpoint inhibitors like HPV16 E6 and E7. Using biochemical and cell biological assays to better understand HPV16 E5, we find that HPV16 E5 localizes to the plasma membrane with an intracellular amino terminus and an extracellular carboxyl-terminus. Further, HPV16 E5 must be expressed on both cells for cell fusion to occur. When the extracellular epitope of HPV16 E5 is targeted with an antibody, the number of bi-nucleated cells decreases.
Hu Lulin [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73126 (United States); Ceresa, Brian P., E-mail: firstname.lastname@example.org [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73126 (United States)
A large number of assays designed for genotyping human papillomaviruses (HPV) have been developed in the last years. They perform within a wide range of analytical sensitivity and specificity values for the different viral types, and are used either for diagnosis, epidemiological studies, evaluation of vaccines and implementing and monitoring of vaccination programs. Methods for specific genotyping of HPV-16 and HPV-18 are also useful for the prevention of cervical cancer in screening programs. Some commercial tests are, in addition, fully or partially automated. Automation of HPV genotyping presents advantages such as the simplicity of the testing procedure for the operator, the ability to process a large number of samples in a short time, and the reduction of human errors from manual operations, allowing a better quality assurance and a reduction of cost. The present review collects information about the current HPV genotyping tests, with special attention to practical aspects influencing their use in clinical laboratories.
Torres, M; Fraile, L; Echevarria, JM; Hernandez Novoa, B; Ortiz, M
High risk human Papillomavirus (HPV) types are the major causative agents of cervical cancer. Reduced expression of major histocompatibility complex class I (MHC I) on HPV-infected cells might be responsible for insufficient T cell response and contribute to HPV-associated malignancy. The viral gene product required for subversion of MHC I synthesis is the E7 oncoprotein. Although it has been suggested that high and low risk HPVs diverge in their ability to dysregulate MHC I expression, it is not known what sequence determinants of HPV-E7 are responsible for this important functional difference. To investigate this, we analyzed the capability to affect MHC I of a set of chimeric E7 variants containing sequence elements from either high risk HPV16 or low risk HPV11. HPV16-E7, but not HPV11-E7, causes significant diminution of mRNA synthesis and surface presentation of MHC I, which depend on histone deacetylase activity. Our experiments demonstrate that the C-terminal region within the zinc finger domain of HPV-E7 is responsible for the contrasting effects of HPV11- and HPV16-E7 on MHC I. By using different loss- and gain-of-function mutants of HPV11- and HPV16-E7, we identify for the first time a residue variation at position 88 that is highly critical for HPV16-E7-mediated suppression of MHC I. Furthermore, our studies suggest that residues at position 78, 80, and 88 build a minimal functional unit within HPV16-E7 required for binding and histone deacetylase recruitment to the MHC I promoter. Taken together, our data provide new insights into how high risk HPV16-E7 dysregulates MHC I for immune evasion.
Heller, Corina; Weisser, Tanja; Mueller-Schickert, Antje; Rufer, Elke; Hoh, Alexander; Leonhardt, Ralf M.; Knittler, Michael R.
Repeat episodes of HPV-related external genital warts reflect recurring or new infections. No study before has been sufficiently powered to delineate how tobacco use, prior history of EGWs and HIV infection affect the risk for new EGWs. Behavioral, laboratory and examination data for 2,835 Multicenter AIDS Cohort Study participants examined at 21,519 semi-annual visits were evaluated. Fourteen percent (391/2835) of men reported or were diagnosed with EGWs at 3% (675/21,519) of study visits. Multivariate analyses showed smoking, prior episodes of EGWs, HIV infection and CD4+ T-lymphocyte count among the infected, each differentially influenced the risk for new EGWs.
Wiley, Dorothy J.; Elashoff, David; Masongsong, Emmanuel V.; Harper, Diane M.; Gylys, Karen H.; Silverberg, Michael J.; Cook, Robert L.; Johnson-Hill, Lisette M.
Background The most common laryngeal mass in children is recurrent respiratory papillomatosis (RRP). Studies have attempted to correlate viral typing and its aggressiveness. Method 29 patients with histologically confirmed RRP enrolled in adjuvant therapies. Patients underwent several surgical interventions. Results HPV genotyping demonstrated 45% HPV-6 and 55% HPV-11. The mean age at the first surgical intervention was 52.39 months (SD=102.28) (range from 4 months to 426 months). The mean number of surgical intervention was 10.39 (SD=7.76) (range from 2 to 30). The mean time of surgical intervals was 4.63 months (SD=4.02) (range from 2 to 24 months). In fourteen patients (48%) tracheotomy was done. All patients who had tracheotomy received alpha-interferon. One of our cases was a male who had pulmonary extension with HPV-6. Conclusion A review of patients with RRP was regarding to HPV genotyping and need for adjuvant therapy and tracheostomy. Mean number of surgical procedure was 10/40 and nearly fourteen patients (48%) need to tracheotomy. The clinical differences between HPV6 and HPV11 disease may not be accurately predictable. Patients with less age and with HPV-11 seemed to have more severe problems, but these differences were not statistically significant which needs much more investigations for reasonable starting point of evaluation for these differences.
Izadi, Farzad; Hamkar, Rasool; Abdolmotallebi, Fereshteh; Jahandideh, Hesam
Human papillomavirus (HPV) is the well-known second most cause of cervical cancer in women worldwide. According to the WHO survey, 70% of the total cervical cancers are associated with types HPV 16 and 18. Presently used prophylactic vaccine for HPV contains mainly capsid protein of L1 virus like particles (VLPs). Correct folding of VLPs and display of neutralizing epitopes are the major constraint for VLP-based vaccines. Further, monoclonal antibodies (mAbs) play a vital role in developing therapeutics and diagnostics. mAbs are also useful for the demonstration of VLP conformation, virus typing and product process assessment as well. In the present study, we have explored the usefulness of mAbs generated against sf-9 expressed HPV 16 VLPs demonstrated as type-specific and conformational dependent against HPV 16 VLPs by ELISA. High affinity and high pseudovirion neutralization titer of mAbs indicated their potential for the development of prophylactic vaccines for HPV. Also, the type-specific and conformational reactivity of the mAbs to HPV 16 VLPs in sf-9 cells by immunofluorescence assay proved their diagnostic potential.
Vidyasagar, P.; Rajan, S.; Praveen, A.; Srikanth, A.; Abhinay, G.; Siva Kumar, V.; Verma, R. R.; Rajendra, L.
Purpose: To study the prognostic value of human papillomavirus (HPV) genotypes in patients with advanced cervical cancer treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Methods and Materials: Between August 1993 and May 2000, 327 patients with advanced squamous cell carcinoma of the cervix (International Federation of Gynecology and Obstetrics stage III/IVA or stage IIB with positive lymph nodes) were eligible for this study. HPV genotypes were determined using the Easychip Registered-Sign HPV genechip. Outcomes were analyzed using Kaplan-Meier survival analysis and the Cox proportional hazards model. Results: We detected 22 HPV genotypes in 323 (98.8%) patients. The leading 4 types were HPV16, 58, 18, and 33. The 5-year overall and disease-specific survival estimates for the entire cohort were 41.9% and 51.4%, respectively. CCRT improved the 5-year disease-specific survival by an absolute 9.8%, but this was not statistically significant (P=.089). There was a significant improvement in disease-specific survival in the CCRT group for HPV18-positive (60.9% vs 30.4%, P=.019) and HPV58-positive (69.3% vs 48.9%, P=.026) patients compared with the RT alone group. In contrast, the differences in survival with CCRT compared with RT alone in the HPV16-positive and HPV-33 positive subgroups were not statistically significant (P=.86 and P=.53, respectively). An improved disease-specific survival was observed for CCRT treated patients infected with both HPV16 and HPV18, but these differenced also were not statistically significant. Conclusions: The HPV genotype may be a useful predictive factor for the effect of CCRT in patients with advanced squamous cell carcinoma of the cervix. Verifying these results in prospective trials could have an impact on tailoring future treatment based on HPV genotype.
Wang, Chun-Chieh [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China) [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, School of Medicine, Taoyuan, Taiwan (China); Lai, Chyong-Huey [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China)] [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Huang, Yi-Ting [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China)] [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Chao, Angel; Chou, Hung-Hsueh [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China)] [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Hong, Ji-Hong, E-mail: email@example.com [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China) [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, School of Medicine, Taoyuan, Taiwan (China)
The objectives of this study were to assess the level of knowledge on HPV and HPV vaccination, and to determine vaccination attitude among Ege university students in Izmir, Turkey. A cross-sectional survey was conducted in first-year English preparatory class. Systematic cluster sampling was applied and 717 (72.6%) of students registered to the 54 classes in 17 different faculties/schools were contacted. Data were collected between April 30 and May 18, 2010, through a self-reported questionnaire including 40 questions. A knowledge score was calculated by summing up the number of correct answers given to the 12 knowledge questions. Analyses were done using t-test, chi-square test, univariate and multivariate logistic regression. The mean age of participants was 19.7±1.5 and 445 (62.1%) were female. Overall, 132 (18.9%) had experienced sexual intercourse, but only 7 of them were female. Among participants, 24.1% had heard of HPV and 25.1% about HPV vaccine. The knowledge item with the highest correct answer rate (32.3%) was that HPV caused cervical cancer. The mean total knowledge score was remarkably poor (1.8±2.6 over 12 items), with 59.6% of respondents having zero as their score. There was no difference in mean knowledge scores between males and females. Higher income, history of sexual intercourse and higher knowledge score were significant factors increasing HPV and vaccine awareness for the whole group, adjusted for gender. Genital cancer history in the family significantly increased awareness, but only among girls. Only three students (0.4%) had already been vaccinated, all being female. Among females, 11.6% intended to be vaccinated vs. 10.1% for males, without any significant difference. Visiting a gynaecologist/urologist in the last three years, a history of genital cancer in the family, vaccine awareness, a higher total knowledge score, and being from the East of Turkey were significant predictors of a positive vaccination attitude. HPVvaccination still remains as a 'hot medical topic' in Turkey, since it hasn't yet become a popular health issue. Based on their age of first intercourse, first year at the university seems to be appropriate timing to inform Turkish girls, whereas it is a bit late for boys. Thus, integration of HPV education into secondary/high school curricula should be considered. PMID:21338218
Durusoy, Raika; Yamazhan, Mustafa; Ta?bakan, Meltem I?ikgöz; Ergin, I?il; Aysin, Murat; Pullukçu, Hüsnü; Yamazhan, Tansu
By means of hybridization of nucleic acid, we detected DNA specific for papilloma virus, type 6a, in a caruncle papilloma of a 45-year-old female patient suffering from genital warts. These findings show that papilloma viruses, which are usually responsible for genital warts, may also induce conjunctival papilloma. PMID:2378155
Fierlbeck, G; Rassner, G; Thiel, H J; Pfister, H
Papillomavirus L2-based vaccines have generally induced low-level or undetectable neutralizing antibodies in standard in vitro assays yet typically protect well against in vivo experimental challenge in animal models. Herein we document that mice vaccinated with an L2 vaccine comprising a fusion protein of the L2 amino acids 11 to 88 of human papillomavirus type 16 (HPV16), HPV18, HPV1, HPV5, and HPV6 were uniformly protected from cervicovaginal challenge with HPV16 pseudovirus, but neutralizing antibodies against HPV16, -31, -33, -45, or -58 were rarely detected in their sera using a standard in vitro neutralization assay. To address this discrepancy, we developed a neutralization assay based on an in vitro infectivity mechanism that more closely mimics the in vivo infectious process, specifically by spaciotemporally separating primary and secondary receptor engagement and correspondingly by altering the timing of exposure of the dominant L2 cross-neutralizing epitopes to the antibodies. With the new assay, titers in the 100 to 10,000 range were measured for most sera, whereas undetectable neutralizing activities were observed with the standard assay. In vitro neutralizing titers measured in the serum of mice after passive transfer of rabbit L2 immune serum correlated with protection from cervicovaginal challenge of the mice. This “L2-based” in vitro neutralization assay should prove useful in critically evaluating the immunogenicity of L2 vaccine candidates in preclinical studies and future clinical trials.
Pang, Yuk-Ying S.; Kines, Rhonda C.; Thompson, Cynthia D.; Lowy, Douglas R.; Schiller, John T.
One of the factors associated with an increased risk of HPV-related malignant transformation may be bacterial and/or viral infections. The aim of our study was to examine whether the presence of infectious agents commonly detected in the genitourinary tract such as herpesviruses (HSV, CMV), and ureaplasmas (Ureaplasma urealyticum, Ureaplasma parvum) may lead to alterations in the expression of the HPV-16 E6 oncogene. Quantitative RT-PCR analysis was used to assess the level of HPV-16 E6 mRNA expression in SiHa cells. The presence of HSV-1 or HSV-2 in SiHa cells caused a 1.5-fold increase in HPV-16 E6 mRNA expression as compared with non-inoculated SiHa cells. Ureaplasma urealyticum presence but not Ureaplasma parvum stimulated the expression of HPV-16 E6 resulting in a nearly five-fold (4.8) up-regulated E6 mRNA level in SiHa cells. Our study is the first to suggest that infection of Ureaplasma urealyticum in an urogenital tract could increase the risk of cervical cancer by overexpression of the HPV E6 oncogene. PMID:24745152
Szostek, S?awa; Zawili?ska, Barbara; Biernat-Sudolska, Ma?gorzata; Kope?, Jolanta; K?eszcz, Ewa; Koprynia, Ma?gorzata; Rojek-Zakrzewska, Danuta; Kosz-Vnenchak, Magdalena
A technique using a biotin-streptavidin polyalkaline phosphatase complex was applied to routinely fixed and processed biopsy specimens of laryngeal papillomata from 45 patients taken over the past 20 years to detect human papilloma virus (HPV) types 6 and 11. Two thirds of both adult and juvenile onset cases were positive for HPV 6 or HPV 11 or both. Five specimens of normal vocal cord epithelium were negative for HPV 6 and 11. The detailed clinical history, endoscopic findings, success of treatment and eventual prognosis were compared with the HPV state of biopsy material for each patient. Patients with multiple confluent lesions when first seen, whose histology showed florid koilocytosis and who had strongly positive reactivity for HPV 6 or 11 present in the surface epithelial cell nuclei, had a poor prognosis requiring multiple endoscopies to control their disease. Images Fig 1
Quiney, R E; Wells, M; Lewis, F A; Terry, R M; Michaels, L; Croft, C B
Over 100 genotypes of human papillomaviruses (HPVs) have been identified as being responsible for unapparent infections or for lesions ranging from benign skin or genital warts to cancer. The pathogenesis of HPV results from complex relationships between viral and host factors, driven in particular by the interplay between the host proteome and the early viral proteins. The E2 protein regulates the transcription, the replication as well as the mitotic segregation of the viral genome through the recruitment of host cell factors to the HPV regulatory region. It is thereby a pivotal factor for the productive viral life cycle and for viral persistence, a major risk factor for cancer development. In addition, the E2 proteins have been shown to engage numerous interactions through which they play important roles in modulating the host cell. Such E2 activities are probably contributing to create cell conditions appropriate for the successive stages of the viral life cycle, and some of these activities have been demonstrated only for the oncogenic high-risk HPV. The recent mapping of E2-host protein-protein interactions with 12 genotypes representative of HPV diversity has shed some light on the large complexity of the host cell hijacking and on its diversity according to viral genotypes. This article reviews the functions of E2 as they emerge from the E2/host proteome interplay, taking into account the large-scale comparative interactomic study.
Muller, Mandy; Demeret, Caroline
Rising rates of human papillomavirus (HPV) infections in recent decades, including external genital warts (EGWs), underscore the need for effective management of this common sexually transmitted disease. Although treatment is a vital aspect that aims primarily to resolve physical symptoms, health care providers must also address the psychosocial burden that typically accompanies diagnosis, treatment, remission, and recurrence. Education and counseling are integral components of care to address the cascade of negative emotional reactions that follow diagnosis, which often include anger, shame, stigma, frustration, and fear. Health care providers should offer patient information that is clear and simple, both verbally and in written form. Research to date has shown that information is most helpful when it is conveyed in a supportive tone and avoids stigmatization. Treatment decisions should consider the patient's preferences and the clinician's ability to offer certain therapies. A locally relevant algorithm and an individualized treatment approach are recommended by various treatment guidelines to improve the chances of compliance and treatment success. Given that success rates are variable, monitoring treatment is also necessary to gauge the patient's response to treatment, local reactions, and the potential need to switch treatments. Patients diagnosed with EGWs should also be screened for other sexually transmitted diseases because coinfection is common. Vaccination is becoming an increasingly important aspect of prevention strategies for HPV infections and should be considered for eligible patients. PMID:24388561
Bourcier, Marc; Bhatia, Neal; Lynde, Charles; Vender, Ronald
The practice of female genital mutilation predates the founding of both Christianity and Islam. Though largely confined among Muslims, the operation is also practiced in some Christian communities in Africa such that female genital mutilation takes place in various forms in more than twenty African countries, Oman, Yemen, the United Arab Emirates, and by some Muslims in Malaysia and Indonesia. In recent decades, ethnic groups which practice female genital mutilation have immigrated to Britain. The main groups are from Eritrea, Ethiopia, Somalia, and Yemen. In their own countries, an estimated 80% of women have had the operation. Female genital mutilation has been illegal in Britain since 1985, but it is practiced illegally or children are sent abroad to undergo the operation typically at age 7-9 years. It is a form of child abuse which poses special problems. The authors review the history of female genital mutilation and describe its medical complications. Assuming that the size of the population in Britain of ethnic groups which practice or favor female genital mutilation remains more or less unchanged, adaptation and acculturation will probably cause the practice to die out within a few generations. Meanwhile, there is much to be done. A conspiracy of silence exists in medical circles as well as widespread ignorance. Moreover, none of a number of well-known obstetric and pediatric textbooks mentions female genital mutilation, while the National Society for the Prevention of Cruelty to Children has neither information nor instructional material. It is high time that the problem was more widely and openly discussed. PMID:7787654
Black, J A; Debelle, G D
Background Increasing knowledge about HPV and HPV vaccine is a potentially important way to increase vaccination rates, yet few education interventions have addressed these topics. We report the results of an education intervention targeting three key groups who have contact with adolescent females. Methods We conducted HPV education intervention sessions during 2008 and 2009 in Guilford County, North Carolina. Parents (n=376), healthcare staff (n=118), and school staff (n=456) attended the one-time sessions and completed self-administered surveys. Analyses used mixed regression models to examine the intervention’s effects on participants’ self-rated HPV knowledge, objectively assessed HPV and HPV vaccine knowledge, and beliefs about HPV vaccine. Results Participants had relatively low levels of objectively assessed HPV and HPV vaccine knowledge prior to the intervention. The education intervention increased self-rated HPV knowledge among all three key groups (all p<0.001), as well as objectively assessed knowledge about many aspects of HPV and HPV vaccine among healthcare and school staff members (all p<0.05). Following the intervention, over 90% of school staff members believed HPV and HPV vaccine education is worthwhile for school personnel and that middle schools are an appropriate venue for this education. Most parents (97%) and school staff members (85%) indicated they would be supportive of school-based vaccination clinics. Conclusions Our education intervention greatly increased HPV and HPV vaccine knowledge among groups influential to the HPV vaccination behaviors of adolescent females. Impact Education interventions represent a simple yet potentially effective strategy for increasing HPV vaccination and garnering stronger support for school-based vaccination clinics.
Reiter, Paul L.; Stubbs, Brenda; Panozzo, Catherine A.; Whitesell, Dianne; Brewer, Noel T.
The objective of this study was to assess the overall prevalence of the human papilloma virus (HPV) infection and distribution of high-risk HPV (hrHPV) types in Greece and evaluate the participation of women in primary and secondary cervical cancer prevention. This was a prospective, cross-sectional study carried out between October 2005 and January 2011 in Greece; 5379 women filled out the study questionnaire anonymously. 5107 women underwent cervical HPV-DNA testing, either by Hybrid Capture 2, followed by restriction fragment length polymorphism-PCR, or by the Abbott Real-Time High-Risk HPV test. Overall, 5.8% (295/5107) of women were positive for hrHPV infection. The most common hrHPV type was HPV-16 (24.8% among infected women; 1.4% overall), followed by HPV types 31, 35, 53, 18, 51, 56, 58, 52, 39, 66, 45, 33, 59, and 68. In respect to primary prevention of cervical cancer, acceptance of anti-HPV vaccination appeared to decrease over time (from 85-89.9% annually during 2005-2008 to 64.4-60.5% during 2009-2010, P<0.001). In respect to secondary prevention, only 30.3% of women had regular (annually for more than 5 years) Pap smears; regular gynecologic examinations, Papanicolaou testing, and knowledge of HPV were all associated with various demographic parameters (age, education, place of residence, occupation, and income). The prevalence of hrHPV infection in Greece is similar to that in other European countries; the most common type is HPV-16. The initially relatively high acceptance of HPV vaccination decreased after licensing of the vaccine. Demographic parameters appear to influence participation in cervical cancer screening. PMID:24977385
Agorastos, Theodoros; Chatzistamatiou, Kimon; Zafrakas, Menelaos; Siamanta, Vagia; Katsamagkas, Taxiarchis; Constantinidis, Theodoros C; Lampropoulos, Alexandros F
We have observed 2 immunosuppressed renal allograft recipients with skin lesions induced by human papillomavirus type 5 (HPV-5). One recipient had multiple pityriasis versicolor-like (PV-like) skin lesions on his arms and trunk, and multiple Bowenoid in-situ skin cancers. The other had 2 warty lesions on the back of her fingers. Structural antigens of human papillomavirus type 5 (HPV-5) were identified
Marvin Lutzner; Odile Croissant; Marie-Françoise Ducasse; Henri Kreis; Jean Crosnier; Gérard Orth
An infection with Human Papilloma Virus (HPV) is directly associated with the development of the cervical and vulvar carcinomas. The infection should be diagnosed and considered in the choice of therapy. Taking no account of HPV infection in histological pictures may lead to overdiagnosis of Ca"0" (CIS). HPV infection is possible to be recognized--in most cases--in cytological and histopathological studies. Cytological and histopathological studies are the basis for other examination methods. The authors, who have been dealing with HPV problem for 10 years, describe characteristic morphological features of the HPV infection based upon original material accompanied by microscopic documentation. The article describes: the types of condylomas, morphological properties of koilocyte and dyskeratocyte with consideration of electronmicroscopic studies, specific features of the infected epithelium, the notion of koilocytic atypia and atypical condylomas, diagnostic difficulties, differentiation with classic dysplasia, the presence of changes typical for Bowen's disease of the cervix and Bowenoid papulosis on the vulva. Morphological diagnosis of the HPV infection worse--in many cases--confirmed by virusologic studies determining the type of the virus in the tissue. It is the authors' opinion that koilocytic atypia is a special form of the intraepithelial neoplasia (CIN, VIN). They emphasize the contribution of the HPV infection to the prevention of cancer of the uterine cervix and vulva. PMID:1966114
Borowicz, K; Walczak, L
The genus betapapillomavirus (betaPV) presently comprises more than 40 virus types including the so-called epidermodysplasia verruciformis (EV)-associated HPV, which were originally detected in EV-patients by Southern blot hybridization. BetaPV are ubiquitous in the general population and frequently establish themselves already during the first weeks of life. Hair follicles are regarded as natural reservoir. About 25% of betaPV detected in adults persist for at least 9 months. Due to very low virus production, seroconversion against betaPV starts sluggishly. Hyperproliferation of keratinocytes in psoriasis patients or after severe burns stimulates virus replication. Massive virus replication only occurs in EV-patients, associated with the induction of disseminated skin lesions with a high risk of malignant conversion. In 75% of EV-patients this can be put down to homozygous, inactivating mutations in the genes EVER1 or EVER2. A transgenic mouse model substantiated the crucial role of increased HPV8 oncogene expression, induced by UV-irradiation or wounding, for tumor induction. PMID:21113568
HIV-positive women are infected with human papillomavirus (HPV) (especially with multiple types), and develop cervical intraepithelial neoplasia (CIN) and cervical cancer more frequently than HIV-negative women. We compared HPV DNA prevalence obtained using a GP5+/6+ PCR assay in cervical exfoliated cells to that in biopsies among 468 HIV-positive women from Nairobi, Kenya. HPV prevalence was higher in cells than biopsies and the difference was greatest in 94 women with a combination normal cytology/normal biopsy (prevalence ratio, PR = 3.7; 95% confidence interval, CI: 2.4-5.7). PR diminished with the increase in lesion severity (PR in 58 women with high-grade squamous intraepithelial lesions (HSIL)/CIN2-3 = 1.1; 95% CI: 1.0-1.2). When HPV-positive, cells contained 2.0- to 4.6-fold more multiple infections than biopsies. Complete or partial agreement between cells and biopsies in the detection of individual HPV types was found in 91% of double HPV-positive pairs. The attribution of CIN2/3 to HPV16 and/or 18 would decrease from 37.6%, when the presence of these types in either cells or biopsies was counted, to 20.2% when it was based on the presence of HPV16 and/or 18 (and no other types) in biopsies. In conclusion, testing HPV on biopsies instead of cells results in decreased detection but not elimination of multiple infections in HIV-positive women. The proportion of CIN2/3 attributable to HPV16 and/or 18 among HIV-positive women, which already appeared to be lower than that in HIV-negative, would then further decrease. The meaning of HPV detection in cells and random biopsy from HIV-positive women with no cervical abnormalities remains unclear. PMID:23444059
De Vuyst, Hugo; Chung, Michael H; Baussano, Iacopo; Mugo, Nelly R; Tenet, Vanessa; van Kemenade, Folkert J; Rana, Farzana S; Sakr, Samah R; Meijer, Chris J L M; Snijders, Peter J F; Franceschi, Silvia
Aim To determine whether immunotherapy with HPV6 L1 virus like particles (VLPs) without adjuvant (VLP immunotherapy) reduces recurrence of genital warts following destructive therapy. Trial design A randomized placebo controlled blinded study of treatment of recurrent genital warts amenable to destructive therapy, conducted independently in Australia and China. Methods Patients received conventional destructive therapy of all evident warts together with intramuscular administration of 1, 5 or 25 µg of VLP immunotherapy, or of placebo immunotherapy (0.9% NaCl), as immunotherapy at week 0 and week 4. Primary outcome, assessed at week 8, was recurrence of visible warts. Results Of 33 protocol compliant Brisbane recipients of placebo immunotherapy, 11 were disease free at two months, and a further 9 demonstrated reduction of > 50% in total wart area. Wart area reduction following destructive treatment correlated with prior duration of disease. Among 102 protocol compliant Brisbane recipients of VLP immunotherapy, disease reduction was significantly greater than among the placebo immunotherapy (50% ± s.e.m. 7%) recipients for subjects receiving 5 µg or 25 µg of VLP immunotherapy/dose (71% ± s.e.m.7%) but not for those receiving 1 µg VLP immunotherapy/dose (42% ± 7%). Of 52 protocol compliant placebo immunotherapy recipients in Wenzhou, 37 were disease free at two months, and a further 8 had > 50% disease reduction. Prior disease duration was much shorter in Wenzhou subject (8.1 ± 1.1 mo) than in Brisbane subjects (53.7 ± 5.5 mo). No significant reduction in mean wart area was observed for the 168 Wenzhou protocol compliant subjects who also received VLP immunotherapy. Conclusions This study confirms the findings in a previous open label trial that administration of VLP immunotherapy may assist in clearance of recurrent genital warts in patients for whom destructive therapy is unsuccessful and that unsuccessful destructive therapy is more common with increasing prior disease duration.
Jardine, David; Lu, Jieqiang; Pang, James; Palmer, Cheryn; Tu, Quanmei; Chuah, John; Frazer, Ian H.