The HPV quadrivalent vaccine has been shown to have high efficacy against infection as well as HPV16/18-positive cervical pre-cancer and HPV6/11-positive genital warts 
. However, the vaccine trials focused exclusively on low risk, mostly non-Hispanic Caucasian women with few (no more than four) sexual partners, who had no history of abnormal cervical cytology, cervical disease or genital warts, and who were highly compliant with the vaccine schedule 
. In this article, we assessed the HPV burden in a high-risk urban minority adolescent female population, and describe the cross-sectional association between the detection of cervical and extra-cervical HPV with vaccine exposure. The cross-sectional data shown here indicates that there is continued detection of cervical HPV with vaccine types after vaccination. This raises questions regarding the ‘real-world’ impact of vaccinating high-risk populations (unlike those studied in the vaccine trials) with potentially frequent prior exposures to vaccine types as well as to other HR-HPV types. Moreover, studying a high-risk population of sexually active adolescent women, we also observe a high prevalence of extra-cervical HPV among both vaccinated and unvaccinated individuals. These observations have important public health implications for future screening and prevention of HPV-related cancer in a high-risk population.
The reported study has strengths and limitations. The current study evaluated HPV at multiple anatomical sites associated with sexual exposure. While it is generally understood that acquisition and prevalence of cervical HPV is at its highest in adolescent women, how this relates to the prevalence and acquisition of HPV in other tissues susceptible to HR-HPV associated tumorigenesis (i.e., the anal epithelium and oral cavity), is not currently known. Among the limitations, it should be noted that because we are specifically targeting sexually active adolescent females, either at the time they receive the HPV vaccine or soon thereafter, our population is older than the targeted age for vaccination, but covers the age range recommended for catch-up vaccination (www.cdc.gov/std/hpv/STDFact-HPV-vaccine-hcp.htm
). In addition, we assessed cross-sectional associations between HPV-DNA infection, vaccine exposure and risk factors. As such, the history of HPV exposure prior to vaccination is not known for those individuals enrolled after vaccine initiation. Furthermore, it is impossible to ascertain via HPV-DNA detection alone if test positivity is equated with true (active, albeit latent) viral infection that may cause neoplastic disease. With longitudinal follow-up, we will be able to assess the HPV incidence and risk factors for “breakthrough”
persistent infections (i.e., repeated detection of an HPV vaccine type in someone who was previously HPV-DNA negative for that type at enrollment) 
When compared to the general MSAHC clinic population (data not shown), the study cohort is younger (mean patient age in 2010 was 18.6 vs. 17.7 in this study) but comparable in terms of prior STIs. The high-risk nature of the population is also evident in the observed prevalent HPV detection. Among the strongest risk factors for detection of cervical and anal HPV (independent of vaccination) were number of sexual partners, anal intercourse, oral-to-anal sex, receipt of a Depo-Provera injection, and history of Chlamydia. Vaccination was significantly associated with cervical and anal HPV detection only after the vaccine types were assessed separately.
Recent evidence suggests the HPV vaccines will impact both cervical and anal HPV co-incidence rates, although efficacy against anal HPV depends on cervical HPV positivity 
. Interestingly, whereas detection of anal HPV vaccine types 6/11 and 18 were significantly lower among vaccinated individuals in this study, the corresponding decrease for HPV16 was not. This was independent of the presence of other HPV types, prior sexual activity and other risk factors. A lower efficacy was observed against persistent anal infection by HPV16 (54.0%) compared to HPV18 (73.6%) in the quadrivalent HPV vaccine male trial intent-to-treat analyses 
. Lower efficacy rates have also been reported in women against anal HPV16 and 18 infections (68.2% and 55.5%, respectively) compared to the cervix (75.8% and 78.6%, respectively) for the bivalent HPV vaccine 
. HPV16 in particular has been shown to be associated with the majority of anal and oropharyngeal neoplasias. The implications of HPV infection at non-cervical sites on vaccine efficacy, however, remain to be evaluated. Moreover, while testing for HPV is approved as an adjunct screening test to Pap cytology for the cervix, testing of other sites (anal or oral) is not routinely performed.
Finally, whereas the odds of detecting HPV vaccine types in the cervix decreased significantly among vaccinated adolescents, the odds of detecting other vaccine related and un-related HR-HPV types did not show consistent decreases with vaccination. We observed significant univariate declines in detection only for HPV16 and 18-related HR-HPV types 31 and 45 in the cervix and anal canal, respectively, as did other studies. While history of previous infection with a vaccine type could not be controlled for in the analyses, it is unlikely the result is solely due to prior exposure given the observed prevalence among unvaccinated individuals. Vaccine efficacy has been shown against persistent infection in the trial cohorts for HPV33, 31, 45 and 51 (with or without HPV16/18 co-infection) 
. The detection of other common HR-HPV types in vaccinated populations that will remain at a high risk of disease has implications for future preventative and screening strategies.
In summary, our data to date suggest continued detection of cervical and extra-cervical infection with HPV vaccine types after vaccination, in addition to other HR-HPV types. This study provides the ‘real-world’ impact of vaccinating high-risk adolescent populations (unlike those studied in the vaccine trials) with potentially frequent prior exposures to HPV vaccine types, as well as to related HR-HPV types. Findings from studies such as this are therefore critical to document the continued burden of HPV and to properly design future multi-type prophylactic HPV vaccines and continued screening strategies to prevent HPV-related disease.