Identifying Longitudinal Risk Factors for Anal High-risk HPV Infections and Strategies to Better Detect Anal High-grade Dysplasia for Anal Cancer Screening in Older Men who have Sex with Men
Human papillomaviruses (HPVs) are common sexually transmitted infections in the epithelium, some genotypes of which are oncogenic and capable of causing cervical and anal cancers. While HPV-associated cervical cancer rates have declined among U.S. women as a result of effective screening and treatment of cervical precancers, anal cancer is increasing in incidence nationwide and is quickly becoming a new threat to public health. While anal cancer is rare in the general U.S. population with an annual incidence rate of 1.8 cases per 100,000 men and women, gay, bisexual, and other men who have sex with men (MSM) have exponentially higher anal cancer incidence rates: 78-137 cases per 100,000 HIV-infected MSM and 5-35 cases per 100,000 HIV-uninfected MSM. The highest estimates for anal cancer in MSM exceed the incidence of the most common cancer in the world (prostate cancer: 120 cases per 100,000), emphasizing the disparate cancer risk in this population. Older MSM are at the highest risk since they have often gone their whole lives without screening, allowing disease to progress unchecked. Risk factors and screening protocols for cervical cancer have long been established and informs anal cancer practices, though for anal cancer, more information is needed and a standard of care remains a work in progress. The purpose of this dissertation is to increase the knowledge and data surrounding anal HPV infections and resulting anal cancer precursors, to inform anal cancer screening and prevention protocols.
This dissertation uses data from the Multicenter AIDS Cohort Study (MACS), the longest running longitudinal study tracking the natural history of HIV/AIDS in MSM, and an independent clinical trial for anal cancer screening in MSM (“Improving Screening Tools for Anal cancer” (ISTA)). Chapter 2 analyzes longitudinal anal HPV data to characterize HPV infection in older MSM, and uses multivariable time-to-event proportional hazards models to identify predictors for incidence and clearance of anal HPV16 and 18, the high-risk HPVs (hrHPVs) accounting for up to 90% of anal cancers. Chapter 3 examines a sample of men with anal biopsy data, to compare anal cytology and hrHPV testing strategies to identify the most effective screening tool to predict histological high-grade squamous intraepithelial lesions (hHSILs): the precursors of anal cancer. Lastly, Chapter 4 assesses self-reported data on testosterone replacement therapy (TRT) and associations with anal cytology test performance and risk for hHSIL. Findings from this dissertation may provide invaluable information to develop standardized anal cancer screening and prevention protocols.