Merck & Co, Inc.

These results suggest that natural HPV infection-elicited antibodies may not provide complete protection over time, however the immune response to the HPV 6/11/16/18 vaccine appears to prevent reinfection or reactivation of disease with vaccine HPV types. Vaccine-related adverse experiences were higher among subjects receiving vaccine, mostly due to increased injection site adverse experiences.

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The 9vHPV vaccine prevents 98% of high-grade cervical dysplasia related to the 9 HPV types covered by the vaccine.• The 9vHPV vaccine prevents 98% of cervical surgeries related to the 9 HPV types covered by the vaccine. • Vaccine did not prevent diseases related to HPV types detected at baseline but reduced diseases related to other HPV types.• While early vaccination in HPV naïve persons is best, sexually active persons may benefit from catch-up vaccination programs.• These data will be important to inform future public health vaccination recommendations. a b s t r a c tObjective. Nine-valent human papillomavirus (9vHPV) vaccine efficacy against disease and cervical surgeries related to all nine vaccine components was assessed compared with a historic placebo population. This was not assessed in the 9vHPV vaccine efficacy trial since the trial was quadrivalent HPV (qHPV) vaccine-controlled, efficacy was measured for the five HPV types covered only by 9vHPV vaccine (HPV31/33/45/52/58), but not the four types covered by both vaccines (HPV6/11/16/18).Methods. Three international, randomized, double-blind studies were conducted using the same methodology. In the 9vHPV vaccine study (NCT00543543), 7106 and 7109 women received 9vHPV or qHPV vaccine, respectively. In the historic qHPV vaccine studies (FUTURE I [NCT00092521] and II [NCT00092534]), 8810 and 8812 women received qHPV vaccine or placebo, respectively, based on the same eligibility criteria. Cervical cytological testing was performed regularly. Biopsy or definitive therapy specimens were assessed for HPV DNA.Results. Among women negative for 14 HPV types prior to vaccination, incidence of high-grade cervical disease (9vHPV, n = 2 cases; placebo, n = 141 cases) and cervical surgery (9vHPV, n = 3 cases; placebo, n = Keywords: Cervical cancer Cervical intraepithelial neoplasia (CIN) HPV Persistent infection Vaccine Vulvar intraepithelial neoplasia (VIN) j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / y g y n o170 cases) related to the nine HPV types was reduced by 98.2% (95% confidence interval [CI], 93.6-99.7) and 97.8% (95% CI, 93.4-99.4), respectively. The 9vHPV vaccine did not prevent disease related to vaccine HPV types detected at baseline, but significantly reduced cervical, vulvar, and vaginal diseases related to other vaccine HPV types.Conclusions. Effective implementation of the 9vHPV vaccine may substantially reduce the burden of HPVrelated diseases and related medical procedures. Trial registrations: clinicaltrials.gov: NCT00543543, NCT00092521, NCT00092534.

Cervical carcinoma and reproductive factors: Collaborative reanalysis of individual data on 16,563 women with cervical carcinoma and 33,542 women without cervical carcinoma from 25 epidemiological studies International Collaboration of Epidemiological Studies of Cervical CancerThe International Collaboration of Epidemiological Studies of Cervical Cancer has combined individual data on 11,161 women with invasive carcinoma, 5,402 women with cervical intraepithelial neoplasia (CIN)3/carcinoma in situ and 33,542 women without cervical carcinoma from 25 epidemiological studies. Relative risks (RRs) and 95% confidence intervals (CIs) of cervical carcinoma in relation to number of full-term pregnancies, and age at first fullterm pregnancy, were calculated conditioning by study, age, lifetime number of sexual partners and age at first sexual intercourse. Number of full-term pregnancies was associated with a risk of invasive cervical carcinoma. After controlling for age at first fullterm pregnancy, the RR for invasive cervical carcinoma among parous women was 1.76 (95% CI: 1.53-2.02) for 7 full-term pregnancies compared with 1-2. For CIN3/carcinoma in situ, no significant trend was found with increasing number of births after controlling for age at first full-term pregnancy among parous women. Early age at first full-term pregnancy was also associated with risk of both invasive cervical carcinoma and CIN3/carcinoma in situ. After controlling for number of full-term pregnancies, the RR for first full-term pregnancy at age <17 years compared with 25 years was 1.77 (95% CI: 1.42-2.23) for invasive cervical carcinoma, and 1.78 (95% CI: 1.26-2.51) for CIN3/carcinoma in situ. Results were similar in analyses restricted to high-risk human papilloma virus (HPV)-positive cases and controls. No relationship was found between cervical HPV positivity and number of fullterm pregnancies, or age at first full-term pregnancy among controls. Differences in reproductive habits may have contributed to differences in cervical cancer incidence between developed and developing countries. ' 2006 Wiley-Liss, Inc.Key words: cervical carcinoma; cervical intraepithelial neoplasia; reproductive factors; full-term pregnancy; age at first full-term pregnancy; collaborative reanalysis; relative risk Parity was one of the earliest risk factors to be associated with cancer risk. Already in 1842, on the basis of death certificates in Verona, Italy, Rigoni-Stern observed that cancers of the uterus (which at that time chiefly originated from the cervix) were more frequent in married women, who tended to be multiparous, whereas breast neoplasms were more common in nulliparae, including nuns. 1Epidemiological studies conducted in the 1950's and 1960's pointed to sexual habits, and subsequent studies to sexual infections, specifically high-risk human papillomavirus (HPV) types, 2 as the key factor in cervical carcinogenesis. Consequently, they tended to consider that the association between reproductive factors and cervical cancer was chiefly accounted for by...

Objective To examine the test performance of care HPV, Hybrid Capture2 (HC2) and visual inspection with acetic acid (VIA) for detection of cytologically diagnosed high-grade cervical lesions or cancer (HSIL+). Design Cross-sectional study. Setting Ocean Road Cancer Institute (ORCI) and Kilimanjaro Christian Medical Center (KCMC), Tanzania. Population Women attending routine cervical cancer screening. Method We enrolled 4080 women (25–60 years) in the study. The women were interviewed on lifestyle habits, and tested for HIV. A cervical specimen for care HPV testing (performed at ORCI and KCMC), and a liquid-based cytology sample for HPV DNA detection using HC2 (performed at Tuebingen University Hospital, Germany) and for cytology assessment (performed at Vejle Hospital, Denmark) were obtained at a gynecological examination. Subsequently, VIA was performed. With cytology as gold standard, the sensitivity and specificity of care HPV, HC2, and VIA for detection of HSIL+ were calculated. Results Altogether, 23.6% had a positive care HPV test, 19.1% had positive HC2 test, and 6.3% had a positive VIA test. The sensitivity/specificity was 88.9%/78.9% for care HPV and 91.1%/83.7%, for HC2. VIA showed a low sensitivity of 31.1% but a high specificity (94.6%) for detection of HSIL+. The sensitivity of care HPV, HC2 and VIA was higher among younger women, and among HIV positive women. VIA triage of care HPV positive women improved specificity, but sensitivity dropped to 27%. Conclusion Our results confirm the low sensitivity of VIA for detection of HSIL+ and further document that care HPV test is promising as a primary screening method for cervical-cancer prevention in low-resource regions. A suitable triage test has to be identified.

BackgroundWe estimated the proportion of cervical intraepithelial neoplasia (CIN) cases attributed to 14 HPV types, including quadrivalent (qHPV) (6/11/16/18) and 9-valent (9vHPV) (6/11/16/18/31/33/45/52/58) vaccine types, by regionMethodsWomen ages 15–26 and 24–45 years from 5 regions were enrolled in qHPV vaccine clinical trials. Among 10,706 women (placebo arms), 1539 CIN1, 945 CIN2/3, and 24 adenocarcinoma in situ (AIS) cases were diagnosed by pathology panel consensus.ResultsPredominant HPV types were 16/51/52/56 (anogenital infection), 16/39/51/52/56 (CIN1), and 16/31/52/58 (CIN2/3). In regions with largest sample sizes, minimal regional variation was observed in 9vHPV type prevalence in CIN1 (~50%) and CIN2/3 (81–85%). Types 31/33/45/52/58 accounted for 25–30% of CIN1 in Latin America and Europe, but 14–18% in North America and Asia. Types 31/33/45/52/58 accounted for 33–38% of CIN2/3 in Latin America (younger women), Europe, and Asia, but 17–18% of CIN2/3 in Latin America (older women) and North America. Non-vaccine HPV types 35/39/51/56/59 had similar or higher prevalence than qHPV types in CIN1 and were attributed to 2–11% of CIN2/3.ConclusionsThe 9vHPV vaccine could potentially prevent the majority of CIN1-3, irrespective of geographic region. Notwithstanding, non-vaccine types 35/39/51/56/59 may still be responsible for some CIN1, and to a lesser extent CIN2/3.