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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.

Human papillomaviruses (HPVs) cause cancer at multiple anatomic sites in men and women, including cervical, oropharyngeal, anal, vulvar, and vaginal cancers in women and oropharyngeal, anal, and penile cancers in men. In this EUROGIN 2014 roadmap, differences in HPV-related cancer and infection burden by gender and anatomic site are reviewed. The proportion of cancers attributable to HPV varies by anatomic site, with nearly 100% of cervical, 88% of anal, and less than 50% of lower genital tract and oropharyngeal cancers attributable to HPV, depending on world region and prevalence of tobacco use. Often mirroring cancer incidence rates, HPV prevalence and infection natural history varies by gender and anatomic site of infection. Oral HPV infection is rare and significantly differs by gender; yet HPV-related cancer incidence at this site is several-fold higher than at either the anal canal or penile epithelium. HPV seroprevalence is significantly higher among women compared to men, likely explaining the differences in age-specific HPV prevalence and incidence patterns observed by gender. Correspondingly, among heterosexual partners, HPV transmission appears higher from women to men. More research is needed to characterize HPV natural history at each anatomic site where HPV causes cancer in men and women, information that is critical to inform the basic science of HPV natural history and the development of future infection and cancer prevention efforts.

HPV16 played a major role in the development of ≥CIN3 irrespective of age, supporting the identification of HPV16 in primary screening for all women. Identification of HPV18 is also warranted, given its significant contribution to AIS and cancer. Identification of non-16/18 genotypes as a pool should provide sufficient information for screening.

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.