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Purpose: Human papillomavirus (HPV) is the causative agent of cervical cancer. Black women are disproportionally diagnosed and have higher mortality from cervical cancer in the United States. Here we describe the prophylactic efficacy and safety of a quadrivalent HPV-6/11/16/18 vaccine in black women., Methods: A total of 700 black women from Latin America, Europe, and North America (aged 16-24 years) received the vaccine or placebo in one of two studies. Analyses focused on the efficacy and safety of the vaccine., Results: Baseline rates of Chlamydia trachomatis infection and history of past pregnancy were more than twice as high in black women compared with the non-black women who were enrolled in these trials. HPV-6/11/16 or 18 DNA was detected in 18% of black women versus 14.6% in non-black women at day 1. For black women, vaccine efficacy against disease caused by HPV-6/11/16/18 was 100% for cervical intraepithelial neoplasia (0 vs. 15 cases; 95% confidence interval, 64.5%-100%) and 100% for vulvar and vaginal intraepithelial neoplasia and condylomata acuminata (0 vs. 17 cases; 95% confidence interval, 69.3%-100%). There were no serious vaccine-related adverse experiences. A similar proportion of pregnancies resulted in live births (75.8% vaccine; 72.7% placebo) and fetal loss (24.2% vaccine; 27.3% placebo)., Conclusions: Prophylactic quadrivalent HPV-6/11/16/18 vaccination of young black women demonstrated high efficacy, safety, and tolerability. HPV vaccination has the potential to reduce cervical cancer-related health disparities both in the United States and around the world., (Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The impact of the prophylactic vaccine against human papillomavirus (HPV) types 6, 11, 16, and 18 (HPV6/11/16/18) on all HPV-associated genital disease was investigated in a population that approximates sexually naive women in that they were "negative to 14 HPV types" and in a mixed population of HPV-exposed and -unexposed women (intention-to-treat group)., Methods: This analysis studied 17 622 women aged 15-26 years who were enrolled in one of two randomized, placebo-controlled, efficacy trials for the HPV6/11/16/18 vaccine (first patient on December 28, 2001, and studies completed July 31, 2007). Vaccine or placebo was given at day 1, month 2, and month 6. All women underwent cervicovaginal sampling and Papanicolaou (Pap) testing at day 1 and every 6-12 months thereafter. Outcomes were any cervical intraepithelial neoplasia; any external anogenital and vaginal lesions; Pap test abnormalities; and procedures such as colposcopy and definitive therapy. Absolute rates are expressed as women with endpoint per 100 person-years at risk., Results: The average follow-up was 3.6 years (maximum of 4.9 years). In the population that was negative to 14 HPV types, vaccination was up to 100% effective in reducing the risk of HPV16/18-related high-grade cervical, vulvar, and vaginal lesions and of HPV6/11-related genital warts. In the intention-to-treat group, vaccination also statistically significantly reduced the risk of any high-grade cervical lesions (19.0% reduction; rate vaccine = 1.43, rate placebo = 1.76, difference = 0.33, 95% confidence interval [CI] = 0.13 to 0.54), vulvar and vaginal lesions (50.7% reduction; rate vaccine = 0.10, rate placebo = 0.20, difference = 0.10, 95% CI = 0.04 to 0.16), genital warts (62.0% reduction; rate vaccine = 0.44, rate placebo = 1.17, difference = 0.72, 95% CI = 0.58 to 0.87), Pap abnormalities (11.3% reduction; rate vaccine = 10.36, rate placebo = 11.68, difference = 1.32, 95% CI = 0.74 to 1.90), and cervical definitive therapy (23.0% reduction; rate vaccine = 1.97, rate placebo = 2.56, difference = 0.59, 95% CI = 0.35 to 0.83), irrespective of causal HPV type., Conclusions: High-coverage HPV vaccination programs among adolescents and young women may result in a rapid reduction of genital warts, cervical cytological abnormalities, and diagnostic and therapeutic procedures. In the longer term, substantial reductions in the rates of cervical, vulvar, and vaginal cancers may follow.

Introduction: As limited data among German women exist about HPV, Chlamydia trachomatis (CT) and Neisseria gonorrhoeae, we report the prevalence of these genital infections and general baseline demographics of the young German women enrolled in the phase III trials of the quadrivalent HPV vaccine., Materials and Methods: German females (n = 437; 9-23 years) were recruited among 3 international phase 3 studies of an HPV-6/11/16/18 vaccine. We present baseline characteristics, prevalence of HPV-6/11/16/18 and, for women aged 16-23, abnormal cervical cytology and sexually transmitted diseases., Results: Chlamydia trachomatis and Neisseria gonorrhoeae prevalence was 5 and 0.3%, respectively. Approximately 17% of participants had HPV-6, 11, 16, or 18 DNA or antibodies. All subjects <17 years were naïve to the four vaccine types., Discussion: The results of the vaccine trials have demonstrated that it is worth administering prophylactic HPV vaccines before sexual debut; however, none of these sexually active German women were positive to all four types and most were positive to only one type. Thus, all women had the potential to benefit from vaccination with a quadrivalent HPV vaccine.

Background: Human papillomavirus (HPV)-6/11/16/18 vaccine reduces the risk of HPV-6/11/16/18-related cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS). Here, its impact on CIN1-3/AIS associated with nonvaccine oncogenic HPV types was evaluated., Methods: We enrolled 17,622 women aged 16-26 years. All underwent cervicovaginal sampling and Pap testing at regular intervals for up to 4 years. HPV genotyping was performed for biopsy samples, and histological diagnoses were determined by a pathology panel. Analyses were conducted among subjects who were negative for 14 HPV types on day 1. Prespecified analyses included infection of 6 months' duration and CIN1-3/AIS due to the 2 and 5 most common HPV types in cervical cancer after HPV types 16 and 18, as well as all tested nonvaccine types., Results: Vaccination reduced the incidence of HPV-31/45 infection by 40.3% (95% confidence interval [CI], 13.9% to 59.0%) and of CIN1-3/AIS by 43.6% (95% CI, 12.9% to 64.1%), respectively. The reduction in HPV-31/33/45/52/58 infection and CIN1-3/AIS was 25.0% (95% CI, 5.0% to 40.9%) and 29.2% (95% CI, 8.3% to 45.5%), respectively. Efficacy for CIN2-3/AIS associated with the 10 nonvaccine HPV types was 32.5% (95% CI, 6.0% to 51.9%). Reductions were most notable for HPV-31., Conclusions: HPV-6/11/16/18 vaccine reduced the risk of CIN2-3/AIS associated with nonvaccine types responsible for approximately 20% of cervical cancers. The clinical benefit of cross-protection is not expected to be fully additive to the efficacy already observed against HPV-6/11/16/18-related disease, because women may have >1 CIN lesion, each associated with a different HPV type., Trial Registration: ClinicalTrials.gov identifiers: NCT00092521 , NCT00092534 , and NCT00092482.

Objective: The purpose of this study was to inform policy regarding human papillomavirus (HPV) vaccination in North America. We measured the clinical impact of HPV-6/-11/-16/-18 vaccination in North American women., Study Design: The study enrolled 21,954 women, the majority aged 16-25, across 5 studies of a quadrivalent HPV vaccine or its HPV-16 vaccine prototype. The North American subjects (n = 5996) were pooled from these trials, and the prevalence of HPV-6/-11/-16/-18 exposure was measured. The impact of vaccination on the burden of anogenital HPV lesions in an intention-to-treat population (regardless of enrollment HPV status) was calculated., Results: At enrollment, the median age was 20 years; 13% of the women had had a Papanicolaou test abnormality, and 76% of the women had negative tests results for all 4 vaccine HPV types. With approximately 3 years of follow-up evaluations in the intention-to-treat population (regardless of enrollment HPV status), vaccination reduced the rate of HPV-16- and -18-related precancers and HPV-6/-11/-16/-18-related genital lesions by 66.4% (95% CI, 42.7%-81.1%) and 57.7% (95% CI, 27.3%-76.3%), respectively., Conclusion: The administration of HPV vaccine to sexually active North American women reduced the burden of HPV-6/-11/-16/-18-related disease. Catch-up vaccination programs in this population are warranted.

Introduction: Cervical cancer is the second most common cancer among women worldwide. In the absence of changing risk or intervention, it is projected that in comparison with 2002 there will be a 40% increase in the number of new cases of cervical cancer by 2020. HPV types 16 and 18 cause 70% of cervical cancers worldwide, 50% of high-grade cervical intraepithelial neoplasias and 25% of low-grade neoplasias. HPV types 6 and 11 are the causative agent of > 90% of genital warts. The aim of this study was to assess the baseline prevalence of infection with HPV 6, 11, 16 and 18 in young Austrian women., Methods: Austrian females aged 16-24 (n = 123) were enrolled in a double-blind, placebo-controlled, randomized phase III trial of a quadrivalent HPV (types 6, 11, 16, 18) vaccine (FUTURE I, ClinicalTrials.gov number NCT00092521). Healthy women who were not pregnant and had no prior history of genital warts or abnormal results on cervical cytologic testing and had fewer than five lifetime sex partners were eligible for enrollment. The study sub-population was recruited primarily from university settings., Results: Analysis of the sexual history of the Austrian subjects showed that 92.7% (114/123) were non-virgins and 46.3% were current smokers. At enrollment, 15 (13.5%) had positive serological or PCR tests for HPV 6, 11, 16 or 18. Serologically, 14 (12.3%) of women were positive to HPV 6, 11, 16 or 18: of these, 13 (11.4%) were positive for HPV 16, four (3.5%) were positive for HPV 18, and one (0.9%) for HPV 6. By PCR all were negative for HPV 6 and 11, whereas seven (6.1%) were positive for HPV 16 and one (0.9%) for HPV 18. Abnormal cytology was observed in 12 (10.3%) women., Discussion: Although the prevalence of vaccine HPV types among young Austrian women with fewer than five lifetime sexual partners was lower than in international data, we observed a high prevalence of abnormal cytology and smoking. These data suggest that a substantial number of Austrian women are at risk for HPV-related disease.

Background: Long-term efficacy evaluations of a quadrivalent HPV type 6/11/16/18 vaccine are ongoing in the Nordic region. As there are limited epidemiological data on HPV infection in Norway, we determined prevalence and identified sociobehavioural correlates of HPV 6/11/16/18 infection in young Norwegian women., Methods: Norwegian (n=898) women, aged 1624 years, were enrolled in a 4-year prospective study. At enrolment and at 6-month intervals thereafter, an interview on behavioural data and a gynaecological examination were undertaken. Genital samples were tested for the L1,E6 and E7 genes of HPV-6/11/16/18, and serum anti-HPV-6/11/16/18 levels were measured using a competitive Luminex immunoassay (cLIA). Results. DNA and seroprevalence of HPV 6, 11, 16 or 18 ranged from 0.9 to 16.3% and 2.6 to 16.2%,respectively; and most infected women (approximately 75%) were infected with only 1 type. Of the HPV DNA positive cases, 54.3, 50.0,47.3 and 38.5% had detectable HPV 6, 11, 16 or 18 antibodies, respectively. More than 50% of the high-grade cervical intraepithelial neoplasia (CIN) cases were HPV-16 or HPV-18 DNA positive. Lifetime number of partners was the strongest and only predictor of sero- and DNA-positivity across the 4 HPV types., Conclusion: Given the high prevalence of HPV infection among young women with mostly single-type infection, and the fact that type-specific HPV screening is not recommended prior to the administration of the quadrivalent HPV vaccine, our data suggest the importance of widespread,rather than targeted, immunisation.

Background: A phase 3 trial was conducted to evaluate the efficacy of a prophylactic quadrivalent vaccine in preventing anogenital diseases associated with human papillomavirus (HPV) types 6, 11, 16, and 18., Methods: In this randomized, placebo-controlled, double-blind trial involving 5455 women between the ages of 16 and 24 years, we assigned 2723 women to receive vaccine and 2732 to receive placebo at day 1, month 2, and month 6. The coprimary composite end points were the incidence of genital warts, vulvar or vaginal intraepithelial neoplasia, or cancer and the incidence of cervical intraepithelial neoplasia, adenocarcinoma in situ, or cancer associated with HPV type 6, 11, 16, or 18. Data for the primary analysis were collected for a per-protocol susceptible population of women who had no virologic evidence of HPV type 6, 11, 16, or 18 through 1 month after administration of the third dose., Results: The women were followed for an average of 3 years after administration of the first dose. In the per-protocol population, those followed for vulvar, vaginal, or perianal disease included 2261 women (83%) in the vaccine group and 2279 (83%) in the placebo group. Those followed for cervical disease included 2241 women (82%) in the vaccine group and 2258 (83%) in the placebo group. Vaccine efficacy was 100% for each of the coprimary end points. In an intention-to-treat analysis, including those with prevalent infection or disease caused by vaccine-type and non-vaccine-type HPV, vaccination reduced the rate of any vulvar or vaginal perianal lesions regardless of the causal HPV type by 34% (95% confidence interval [CI], 15 to 49), and the rate of cervical lesions regardless of the causal HPV type by 20% (95% CI, 8 to 31)., Conclusions: The quadrivalent vaccine significantly reduced the incidence of HPV-associated anogenital diseases in young women. (ClinicalTrials.gov number, NCT00092521 [ClinicalTrials.gov].)., (Copyright 2007 Massachusetts Medical Society.)

GARDASIL (Merck, Whitehouse Station, NJ) is a non-infectious recombinant, quadrivalent vaccine prepared from the highly purified virus-like particles (VLPs) of the major capsid proteins of human papillomavirus (HPV) types 6, 11, 16, and 18. GARDASIL is the first vaccine approved for use in women aged 9-26 years for the prevention of cervical cancer and genital warts, as well as vulvar and vaginal precancerous lesions. This report describes some of the key preclinical efforts, achievements in pharmaceutical development, in vivo animal evaluation, and clinical trial data.