The study was reported for 3,819 women with no history of any HPV infections, genital warts or cervical diseases. Subjects were randomized into groups that received either vaccine or placebo and followed for 2 years. Among the vaccine group of older naive women, Gardasil was 90.5% effective in preventing genital infections and diseases related to HPV types 6, 11, 16, and 18. When evaluating only HPV 16 and 18, the vaccine blocked 83.1% of infections and associated diseases. The efficacy dropped to 31% when women with any HPV infection were also included in the study population.

Aim: This work describes the human papillomavirus (HPV) prevalence and the HPV type distribution in a large series of vaginal intraepithelial neoplasia (VAIN) grades 2/3 and vaginal cancer worldwide.Methods: We analysed 189 VAIN 2/3 and 408 invasive vaginal cancer cases collected from 31 countries from 1986 to 2011. After histopathological evaluation of sectioned formalin-fixed paraffin-embedded samples, HPV DNA detection and typing was performed using the SPF-10/DNA enzyme immunoassay (DEIA)/LiPA(25) system (version 1). A subset of 146 vaginal cancers was tested for p16(INK4a) expression, a cellular surrogate marker for HPV transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance.Results: HPV DNA was detected in 74% (95% confidence interval (CI): 70-78%) of invasive cancers and in 96% (95% CI: 92-98%) of VAIN 2/3. Among cancers, the highest detection rates were observed in warty-basaloid subtype of squamous cell carcinomas, and in younger ages. Concerning the type-specific distribution, HPV16 was the most frequently type detected in both precancerous and cancerous lesions (59%). p16(INK4a) overexpression was found in 87% of HPV DNA positive vaginal cancer cases.Conclusions: HPV was identified in a large proportion of invasive vaginal cancers and in almost all VAIN 2/3. HPV16 was the most common type detected. A large impact in the reduction of the burden of vaginal neoplastic lesions is expected among vaccinated cohorts. (c) 2014 Elsevier Ltd. All rights reserved.

Genital warts (GWs) and laryngeal papillomatosis (LP) are two usually benign pathologies related to infection with human papillomaviruses (HPVs), mainly HPV6 and HPV11. The aim of this work was to describe the genetic diversity of HPV6 and HPV11 isolates found in GWs and LPs, and to analyse the differential involvement of viral variants in either lesion. A total of 231 samples diagnosed as GWs (n = 198) or LP (n = 33) and caused by HPV6 or HPV11 monoinfections were analysed. The phylogenetic relationships of the retrieved viral sequences were explored. We have identified the long control region and the intergenic E2-L2 region as the two most variable regions in both HPV6 and HPV11 genomes. We have generated new HPV6 (n = 166) or HPV11 (n = 65) partial sequences from GWs and LPs lesions spanning both regions and studied them in the context of all available sequences of both types (final n = 412). Our results show a significant (p <0.01) differential presence of HPV6 variants among both pathologies, with HPV6 B variants being preferentially found in GW versus LP samples. No differential involvement of HPV11 variants was observed. Our findings suggest that different HPV6 variants may either show differential tropism or have different potential to induce lesions in different epithelia.

BACKGROUND: Approximately 40% of penile squamous cell carcinomas (SCC) are human papillomavirus (HPV) related and there is controversy regarding the prognostic impact of HPV in this subset of tumors. DESIGN: SCCs (202 cases) were tested for HPV using SPF-10 PCR. They were categorized in low and high-grade and according to warty and/or basaloid (WB) features. High-grade tumors had anaplastic cells, high nuclear/cytoplasmic ratio, pleomorphism, coarse chromatin, prominent nucleoli, irregular nuclear membrane, and high mitotic/apoptotic rate. RESULTS: HPV was found in 64 (32%) cases. High-grade features were present in 84 (42%) of all cases. Seventy tumors (35%) showed warty and/or basaloid features. A strong association was observed between histologic grade and HPV status (P < 0.00001). Tumors with warty-basaloid features showed a stronger association (P=0.016) than tumors without these features (P=0.04). CONCLUSION: HPV-related penile SCCs were of higher grade than HPV-unrelated tumors. Most HPV-related WB carcinomas were of high grade. One-third of high-grade non-WB carcinomas were also associated with HPV. Knowing the impact of histological grade in the prognosis of patients with penile carcinomas the role of HPV as an adverse factor needs to be considered.

BACKGROUND:Previous analyses from a randomised trial in women aged 24-45 years have shown the quadrivalent human papillomavirus (qHPV) vaccine to be efficacious in the prevention of infection, cervical intraepithelial neoplasia (CIN), and external genital lesions (EGLs) related to HPV 6/11/16/18. In this report, we present end-of-study efficacy, safety, and immunogenicity data with a median follow-up time of 4.0 years. METHODS:We enrolled 3819 24-45-year-old women with no history of cervical disease or genital warts in the past 5 years. Women received quadrivalent vaccine or placebo at day 1, and at months 2 and 6. Ascertainment of CIN/EGL was accomplished through Pap testing, genital inspection, and cervicovaginal sampling (every 6 months). The main analysis was conducted in a per-protocol efficacy population (that received three doses, was naive to the relevant HPV types at day 1, and remained free of infection through month 7). Efficacy was also estimated in other naive and non-naive populations. RESULTS:Vaccine efficacy against the combined incidence of persistent infection, CIN/EGL related to HPV6/11/16/18 in the per-protocol population was 88.7% (95% CI: 78.1, 94.8). Efficacy for women who were seropositive and DNA negative for the relevant vaccine HPV type at the time of enrolment who received at least 1 dose was 66.9% (95% CI: 4.3, 90.6). At month 48, 91.5, 92.0, 97.4, and 47.9% of vaccinated women were seropositive to HPV 6/11/16/18, respectively. No serious vaccine-related adverse experiences were reported. CONCLUSIONS:The qHPV vaccine demonstrated high efficacy, immunogenicity, and acceptable safety in women aged 24-45 years, regardless of previous exposure to HPV vaccine type.

A skeleton structure, which consists of dielectric cylinders connecting the tetrahedral and octahedral centers among close-packed template spheres, is found in a titania inverse opal prepared by the template-directed method using monodispersed polystyrene particles of size 270nm. The skeleton structure can have two complete photonic band gaps.

Cervical cancer risk is associated with low education even in an unscreened population, but it is not clear whether human papillomavirus (HPV) infection follows the same pattern. Two large multicentric studies (case–control studies of cervical cancer and HPV prevalence survey) including nearly 20 000 women. GP5+/GP6+ PCR was used to detect HPV. Education level was consistently associated with cervical cancer risk (odds ratio (OR) for 0 and >5 years vs 1–5 years=1.50, 95% confidence interval (CI): 1.25–1.80 and 0.69, 95% CI: 0.57–0.82, respectively, P for trend <0.0001). In contrast, no association emerged between education level and HPV infection in either of the two IARC studies. A majority of the women studied had never had a Pap smear. The association between low education level and cervical cancer was most strongly attenuated by adjustment for age at first sexual intercourse and first pregnancy. Parity and screening history (but not lifetime number of sexual partners, husband's extramarital sexual relationships, and smoking) also seemed to be important confounding factors. The excess of cervical cancer found in women with a low socio-economic status seems, therefore, not to be explained by a concomitant excess of HPV prevalence, but rather by early events in a woman's sexually active life that may modify the cancer-causing potential of HPV infection.

Little is known about the dynamics of human papillomavirus (HPV) infection and subsequent development of high-grade cervical intraepithelial neoplasia (CIN2/3), particularly in women >30 years of age. This information is needed to assess the impact of HPV vaccines and consider new screening strategies. A cohort of 1728 women 15-85 years old with normal cytology at baseline was followed every 6 months for an average of 9 years. Women with squamous intraepithelial lesions were referred for biopsy and treatment. The Kaplan-Meier method was used to estimate the median duration of infection and Cox regression analysis was undertaken to assess determinants of clearance and risk of CIN2/3 associated with HPV persistence. No difference in the likelihood of clearance was observed by HPV type or woman's age, with the exception of lower clearance for HPV16 infection in women under 30 years of age. Viral load was inversely associated with clearance. In conclusion, viral load is the main determinant of persistence, and persistence of HPV16 infections carry a higher risk of CIN2/3.

BackgroundQuadrivalent human papillomavirus (HPV types 6/11/16/18) L1 VLP vaccine is highly effective in preventing HPV 6/11/16/18-related cervical and external genital disease. Herein, we evaluated the impact of the quadrivalent HPV 6/11/16/18 L1 VLP vaccine on prevention of HPV-associated cervico-genital lesions in a broad population of sexually active European women.MethodsFemale subjects (N = 9265) aged 16-24 with four or fewer lifetime sexual partners were enrolled and randomized to quadrivalent HPV vaccine or placebo. Subjects underwent cervicovaginal sampling for HPV DNA detection. Papanicolaou testing and anti-HPV 6/11/16/18 serology testing was also performed.ResultsVaccine efficacy against lesions representing immediate cervical cancer precursors (cervical intraepithelial neoplasia grade 2/3 or adenocarcinoma in situ) related to HPV 6/11/16/18 in the per-protocol population was 100.0%[95% confidence interval (95% CI), 89.8-100.0]. Efficacy against external genital lesions (vulvar or vaginal intraepithelial neoplasia, condyloma, vulvar or vaginal cancer) related to vaccine HPV types in the per-protocol European population was 99.0% (95% CI, 94.4-100.0).ConclusionThese data demonstrate that quadrivalent HPV 6/11/16/18 vaccination programs in 16- to 24-year-old European women can be beneficial.NCT0009252, NCT00092534, NCT00092495.

Transmission routes of Kaposi's sarcoma-associated herpes virus (KSHV) in the general population are poorly understood. Sexual transmission appears to be common in homosexual men, but heterosexual transmission has not been clearly documented. This study aims to estimate the prevalence of KSHV in the female general populations of Argentina, Colombia, Costa Rica, Nigeria, Spain, Vietnam, Thailand and Korea to explore geographical variation and potential heterosexual transmission. Samples and questionnaire data were available from a study organized by the International Agency for Research on Cancer (IARC) to estimate the prevalence of distinct sexually transmitted infections. The study includes 10,963 women from 10 centers with questionnaire information available on socio-demographic, reproductive and sexual lifetime experiences, smoking habits. HPV DNA detection was previously measured. Antibodies against KSHV encoded K8.1 and orf73 were determined. Prevalence of antibodies to any of the two antigens k8.1 or orf73 was 13.9 percent with an important geographical variation (range = Nigeria 46%–3.8% in Spain). Antibodies increased with increasing age particularly in high prevalent countries such as Nigeria, Colombia and Costa Rica. KSHV was not related to education, age at first sexual intercourse, number of sexual partners, number of children, patterns of use of oral contraceptives or presence of cervical HPV DNA. A decreased prevalence was observed with increasing number of cigarettes smoked per day (p = 0.000). The study provides reliable and comparable estimates of KSHV in diverse cultural settings across four continents and provides a powerful indication of absence of heterosexual transmission of KSHV.

Early age at first sexual intercourse (AFSI) has long been associated with an increased risk of invasive cervical carcinoma (ICC). Age at first pregnancy (AFP) and ICC have been investigated less, although AFSI and AFP are strongly interrelated in most developing countries. A pooled analysis of case–control studies on ICC from eight developing countries with 1864 cases and 1719 controls investigated the roles of AFSI, AFP, and ICC risk. Age at first sexual intercourse, AFP and age at first marriage (AFM) were highly interrelated and had similar ICC risk estimates. Compared with women with AFSI ⩾21 years, the odds ratio (OR) of ICC was 1.80 (95% CI: 1.50–2.39) among women with AFSI 17–20 years and 2.31 (95% CI: 1.85–2.87) for AFSI ⩽16 years ( P -trend <0.001). No statistical interaction was detected between AFSI and any established risk factors for ICC. The ICC risk was 2.4-fold among those who reported AFSI and AFP at ⩽16 years compared with those with AFSI and AFP at ⩾21 years. These data confirm AFSI and AFB as risk factors for ICC in eight developing countries, but any independent effects of these two events could not be distinguished.

We conducted a hospital‐based case‐control study in Algiers, Algeria. A total of 198 cervical carcinoma (CC) cases (including 15 adeno‐ and adenosquamous carcinomas) and 202 age‐matched control women were included. Human papillomavirus (HPV) DNA in cervical cells was evaluated using a PCR assay. Odds ratios and corresponding confidence intervals were computed by means of unconditional multiple logistic regression models. HPV infection was detected in 97.7% of CC cases and 12.4% of control women (OR = 635). Nineteen different HPV types were found. HPV 16 was the most common type in both CC cases and control women, followed by HPV 18 and 45. Twelve types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 66 and 73) were found as single infections in CC cases. Multiple HPV infections did not show a higher odds ratio for CC than single infections. In addition to HPV infection, husband's extramarital sexual relationships with other women (OR = 4.8) or prostitutes (OR = 3.2), residing in a rural environment for most of one's life (OR = 4.9) and indicators of poor sanitation or poor hygiene were the strongest risk factors for CC. Oral contraceptive use was unrelated to CC risk, while multiparity emerged as a significant risk factor after adjustment for sexual habits. Intrauterine device users showed a lower CC risk than nonusers. The role of major risk factors, except inside toilet, was confirmed in the analysis restricted to HPV‐positive women. The distribution of HPV types in CC cases and control women in Algeria is more similar to the one found in Europe than the one in sub‐Saharan Africa, where HPV 16 is less prevalent. A vaccine against HPV 16 and 18 may be effective in more than 3/4 of CCs in Algeria.

Background The proportion of women infected with human papillomavirus (HPV) varies greatly across populations, as might the distribution of HPV types. We aimed to compare HPV-type distribution in representative samples of women from different world regions.Methods Women were randomly selected from the general population of 13 areas from 11 countries (Nigeria, India, Vietnam, Thailand, Korea, Colombia, Argentina, Chile, the Netherlands, Italy, and Spain). A standardised protocol was used for cervical specimen collection. All HPV testing was by GP5+/6+ PCR-based EIA. The proportion of HPV-positive women infected with different HPV types was compared by study area and between pooled regions with age-adjusted odds ratios (ORs) with corresponding 95% floating CIS.Findings 15 613 women aged 15-74 years without cytological abnormalities were included in a pooled analysis. Age-standardised HPV prevalence varied nearly 20 times between populations, from 1.4% (95% CI 0.5-2.2) in Spain to 25.6% (22.4-28.8) in Nigeria. Although both overall HPV prevalence and HPV16 prevalence were highest in sub-Saharan Africa, HPV-positive women in Europe were significantly more likely to be infected with HPV16 than were those in sub-Saharan Africa (OR 2.64, p=0.0002), and were significantly less likely to be infected with high-risk HPV types other than HPV16 (OR 0.57, p=0.004) and/or low-risk HPV types (OR 0.44. p=0.0002). Women from South America had HPV-type distribution in between those from sub-Saharan Africa and Europe. Heterogeneity between areas of Asia was significant.Interpretation Heterogeneity in HPV type distribution among women from different populations should be taken into account when developing screening tests for the virus and predicting the effect of vaccines on the incidence of infection.