Natural History of CIN and HPV in HPV Vaccinated Youth with PHIV

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Project Summary/Abstract Worldwide, over 300,000 women die each year from squamous cell cancers (SCC) of the cervix caused by the high risk human papillomavirus (hrHPV). The development of the HPV vaccine has been a transforming event, capable of preventing cervical cancer globally. HIV infection is an established risk factor for HPV persistence, progression to CIN2+, and HPV-associated cancers. The majority of perinatal HPV appears to be transient. However, the ability of infants with perinatal HIV infection (PHIV) to clear this infection is unknown. What is known is that abnormal cytology is one of the more common diagnosed morbidities in PHIV women. One of the pressing questions worldwide is “what is the efficacy in vaccinating PHIV children?” In a recent study within PHACS of HPV-vaccinated youth, we found that those with PHIV had HPV antibody titers lower than uninfected youth and most disturbingly, their rate of abnormal cytology was exceedingly high: the incidence of abnormal cytology was 15.0 and 2.9 /100 person-years for PHIV and uninfected, respectively. It remains unclear whether this reflects vaccine failure or disease due to non-vaccine HPV types. Our findings led to a sub-study within PHACS supported by the NCI to screen women with abnormal cytology with colposcopy and perform HPV genotyping on cervical lesions. This proposal plans to take advantage of women in this sub-study to understand the natural history of CIN 1 or 2. We are proposing the following Aims: Among YAPHIV women who have been vaccinated against HPV, we will examine: 1. the rate of and risk factors for regression and persistence/progression of HPV-associated CIN1 or 2. YAPHIV found to have CIN 1 or 2 will be followed prospectively by colposcopy, cytology and HPV genotyping. 2. the prevalence of CIN 2+ in those testing positive for hrHPV with/without p16-Ki67 dual staining. 3. the rate of and risk factors for regression and persistence/progression of hrHPV infections. Women in aim 2 with normal cytology and no CIN will be followed prospectively by annual cytology and HPV genotyping. Among PHIV Men, we will examine: 4. the prevalence of and natural history of oral HPV in HPV-vaccinated and unvaccinated PHIV men. Oral rinses obtained for PHACS bio-repository in men every three years will be tested for HPV genotyping. In summary, PHACS AMP-Up, a prospective cohort study, is an exceptional opportunity to understand the natural history of hrHPV and CIN 1 or 2 in PHIV women and oral HPV in PHIV men. The results of this study will be critical for developing clinical and policy guidelines for HPV vaccination strategies and cervical cancer screening among young men and women in resourced and resource poor settings.