Impact of human papillomavirus (HPV)-6/11/16/18 vaccine on all HPV-associated genital diseases in young women.

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.

Systematic review of human papillomavirus prevalence in invasive penile cancer.

OBJECTIVE: Type-specific prevalence data of human papillomavirus (HPV) DNA in penile carcinoma are needed to determine the potential impact of HPV prophylactic vaccines, assuming demonstrated efficacy in men. METHODS: A review was conducted using search terms including HPV and penile cancer. Studies using polymerase chain reaction (PCR) assays for HPV DNA detection in invasive penile carcinoma were included. RESULTS: A total of 1,266 squamous cell carcinoma (SCC) cases contributed data from 30 studies. The number of SCC was similar in Europe (28.2%), North America (27.6%), South America (23.9%) and Asia (20.4%). All SCC were histologically confirmed with biopsies for DNA detection. Most commonly used PCR primers were type-specific (35.2%), and combination PCR (18.2%). HPV prevalence was 47.9%, ranging from 22.4% in verrucous SCC to 66.3% for the basaloid/warty subtypes. HPV16 (30.8%), HPV6 (6.7%) and HPV18 (6.6%) were the most prevalent types. HPV16 and/or HPV 18 prevalence was 36.7%. CONCLUSIONS: HPV DNA was detected in half of SCC, with HPV16 being the most common type. If proven efficacious in men, prophylactic vaccines targeting carcinogenic types HPV16 and 18 could potentially reduce approximately one-third of incident SCC.

Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18.

Human papillomavirus (HPV) infection causes cervical cancer and genital warts. Young women (1106) were randomized to receive one of three formulations of a quadrivalent HPV (Types 6/11/16/18) L1 virus-like particle (VLP) vaccine or one of two placebo formulations. The goal was to assess vaccine safety and immunogenicity in baseline HPV 6/11/16 or 18-naïve and previously infected subjects. All three formulations were highly immunogenic. At Month 2 (postdose 1), among women with vaccine-type antibodies at baseline, vaccine-induced anti-HPV responses were approximately 12- to 26-fold higher than those observed in baseline-naïve women, suggesting an anamnestic response. Following an initial, similar sized decline, anti-HPV responses plateaued and remained stable through end-of-study (3.0 years). No vaccine-related serious adverse experiences were reported.