**7. Primary prevention of HPV/cervical cancer**

Given the millions of new HPV infections/ year in 14-44 year olds primary prevention of HPV infections should be a priority. Consistent and correct use of condoms has been associated with reduction in risk for acquisition of genital HPV infection, including genital warts, CIN and cervical cancer (Winer et al. 2006; Vaccarella et al. 2006; Manhart and Koutsky 2002) although data are limited in the HIV setting. Male circumcision (MC) has been shown to reduce by reduce the risk of sexual HIV transmission from female to male by 60% (http://www.who.int/hiv/topics/malecircumcision/en/index.html) in randomized clinical trials. MC was also associated with a lower incidence of multiple high-risk HPV types and increased clearance of HR-HPVs as compared to controls (14.8% vs 22.3%, respectively) in Uganda (Gray et al. 2010); however, MC was not associated with decreased incidence or increased clearance of HR-HPV in the female partners of circumcised men 24 months after the procedure, as compared to partners of men in the control group (Tobian et al. 2011) However, MC has long been associated with reduced risk of cervical cancer in the wives of circumcised men; therefore further study is warranted.

Finally, two HPV preventive vaccines are now available, one quadrivalent, providing protection against HPV types 16, 18, 6, 11, and the second bivalent, protecting against HPV types 16 and 18 only. In the initial trials of these vaccines, there was >95% -100% protection against incident infection with vaccine subtypes in women not previously infected with those subtypes and in CIN2 or greater related to HPV-16 or 18 (FUTURE II Study Group, 2007; Villa et al. 2005; Paavonen et al. 2009, Garland et al. 2007) vaccine effectiveness was maintained through over 7 years of follow-up (FUTURE I/II Study Group 2010). Although there are other high risk HPV types, types 16 and 18 are responsible for approximately 70% of invasive cervical cancers worldwide (de Sanjose et al. 2010). Recent HPV seroprevalence studies in HIV+ African women found that 65% were seropositive for one of the vaccine subtypes (Firnhaber 2011), suggesting that early vaccination may provide significant

Cervical Cancer Screening and Prevention for HIV-Infected Women in the Developing World 247

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protection. However, a recent review found that HIV-infected women in different geographic regions (including Zambia, Brazil, US) appear to be infected with less prevalent HR-HPV types as compared to the general population (McKenzie et al. 2010) . As yet there are limited data on safety, immune response and efficacy of the HPV vaccine in HIV+ women, although studies are on-going. Although data on the safety of the quadrivalent vaccine in HIV-infected children has been demonstrated, efficacy of the currently available HPV vaccines in women or girls with HIV has not yet been established (Levin et al. 2010).

Given the high rates of HPV and cervical cancer in countries with limited health resources, initiatives to introduce HPV vaccination for young people prior to the initiation of sexual activity in these settings are critical. The HPV vaccine is the most expensive vaccine ever developed and costs must be lowered to make this a feasible intervention in the developing world. Fortunately, groups such as GAVI and others are working with governments and other potential donors, as well as with the vaccine makers, to make these vaccines more accessible in areas where they are needed most. Given the high prevalence of both HIV and HPV in many low resource settings and the virologic synergy between these two viruses, with increased rates of HPV-related disease in HIV+ individuals, HIV+ women may be a particular target group for vaccine administration. Furthermore, with improved access to antiretroviral treatment and greater longevity, an increasing number of girls who have been perinatally infected with HIV will be living into adulthood and these girls may particularly benefit from HPV vaccination.

Mathematical models estimate that reduction in incidence and mortality of cervical cancer will be greatest in low/middle income countries with no or limited screening and that HPV vaccination may be cost-effective if cost <\$10–25/vaccinated girl (Kim JJ et al. 2008). Currently, the WHO recommends including routine HPV vaccination in national immunization programs, providing prevention of cervical cancer is a public health priority, programmatically feasible, cost-effective, and has sustainable financing (WHO 2009). HIV infection is not considered a contraindication to HPV vaccination (CDC 2007; ACOG 2010; CDC 2009).
