Abstract SY12-01: HPV vaccines: The opportunity to prevent multiple cancers
Authors: Giuliano Anna R. 
Published: August 2012

Abstract
Identification of the viral etiology of (human papillomavirus [HPV]) and subsequent prevention of cervical cancer has been driven by the desire to reduce the high case burden and associated mortality world wide, predominantly in low and middle income countries, and among underserved women in the US. Consequently, for decades research has focused intensely on understanding the natural history of HPV infections in women, utilization of HPV testing as a cervical cancer screening paradigm, and development and deployment of an HPV vaccine to prevent cervical cancer. Worldwide 70% of invasive cervical cancer cases are caused by HPV types 16 or 18, with HPV 16 being the most common type detected (55% of cases), followed by HPV 18 (15% of cases). Other oncogenic HPV types including 31, 33, 35, 45, 52 and 58 that are phylogenetically related to HPV 16 and 18 account for an additional 18% of all cervical cancer cases. Results from randomized controlled trials (RCTs) of prophylactic HPV vaccines in females consistently showed high efficacy in preventing infection and subsequent high grade precancerous cervical lesions associated with vaccine-type oncogenic HPV (HPV 16 and 18) as well as phylogenetically-related oncogenic HPV types. These data led to licensure of two HPV vaccines in numerous countries in 2006 and subsequent years. Today, HPV vaccination is most commonly considered for cervical cancer prevention. However, HPV causes multiple cancers in both men and women; HPV 16 is a cause of vulvar, vaginal and anal cancers in women, as well as anal, penile, and oropharyngeal cancers in men. While cervical cancer incidence is declining, the incidence of anal cancers and HPV related oropharyngeal cancers is rising. This increase in cancer incidence is occurring for cancers for which there is no routine method for screening and early detection, as there is for cervical cancer. Therefore there is tremendous interest in exploring whether a single vaccine can prevent multiple cancers in men and women. Within a couple of years of initial quadrivalent HPV (qHPV) vaccine licensure the cancer prevention indication for the qHPV vaccine was extended to include prevention of vaginal and vulvar cancers based on the weight of evidence from Phase III trials. While numerous large Phase III HPV vaccine efficacy trials have been completed in females, HPV vaccine efficacy testing in men has been much less extensive.
To date only one Phase III HPV vaccine trial has been completed in males. The trial included 3463 heterosexual men (HM) and 602 men who have sex with men (MSM) ages 16-26 years enrolled from 71 sites in 18 countries. Almost all males vaccinated (97.4-99.2%) sero-converted for HPV vaccine types by month 7. At month 36 post-vaccination, 88.95, 94.0%, 97.9%, and 57% of subjects were still seropositive for HPV 6, 11, 16, and 18 respectively. In per protocol (PPE) analyses, qHPV vaccine significantly decreased external genital HPV 6, 11, 16, 18 infection related lesions by 90.4% (95% CI, 69.2-98.1) as well as persistent infection 85.6% (97.5% CI, 73.4-92.9). In addition, among MSM qHPV vaccine significantly decreased persistent anal canal infection 94.9% (95% CI: 80.4-99.4) and AIN 2/3 74.9% (95% CI: 8.8-95.4). First licensure of the qHPV vaccine for males occurred in 2009 and as of 2010 the qHPV vaccine was indicated for the prevention of cervical, vulvar, vaginal, and anal cancers in women, and anal cancer in men. Similar to reports of safety among females, a full safety analysis in males indicates that while the proportion of subjects who reported &gt;1 adverse event (AE) was relatively high at 60.1% and 53.7% among vaccine vs. placebo recipients, the incidence of &gt;1 systemic AEs was low (31.7% and 31.4%), and there were no vaccine-related serious AEs or deaths among males.
While much progress has been made since the identification of HPV as the cause of cervical cancer, not all are benefiting from the currently licensed vaccines. Only 32% of age eligible US females have received the HPV vaccine, uptake in males is currently extremely low, and vaccine dissemination in most low and middle income countries, countries in greatest need of the vaccine, is nearly non-existent. In addition, while the biology would suggest that the HPV vaccine should prevent penile and oropharyngeal cancers, data to support this assumption are lacking.
In conclusion, HPV is potent carcinogen that causes multiple related cancers in men and women. Two licensed HPV vaccines provide outstanding efficacy against cervical cancer and the qHPV vaccine has demonstrated efficacy against cervical, vaginal, vulvar, and anal cancers. Both vaccines have a favorable safety profile with on-going Phase IV studies to assess safety and effectiveness. Assessment of HPV carcinogenicity at other anatomic sites is under way as are planned trials to test the efficacy of the HPV vaccine to prevent cancer at multiple anatomic sites in men. However, to fully realize the cancer prevention potential of this vaccine there will need to be broad dissemination of the vaccine to ensure high population coverage. Herein lies our current and future public health challenge.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY12-01. doi:1538-7445.AM2012-SY12-01