Core Support for Cancer Center

Albert Einstein College Of Medicine, Bronx NY

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Abstract

Cervical, anal, and oropharyngeal cancers are causally associated with high ?-HPV, particularly HPV16. The risks of these cancers are increased several-fold in persons living with HIV (PLWH) despite the widespread use of cART, and these risks increase further with diminishing CD4 count. Recently, a prospective nested case-control study by our research group (JAMA Oncol, 2016) found that not only HPV16 - but also certain ?-/?-HPV types - were strongly (independently) associated with incident head and neck squamous cell cancer (HNSCC). The odds ratios (ORs) ranged from OR=2.5 to OR=7.4 depending on the ?-/?-HPV type. Moreover, while HPV16 was only associated with tumors of the oropharynx, the ?-/?-HPV were prospectively associated with the incident development of tumors of the larynx, hypopharynx, oral cavity, as well as the oropharynx. In fact, ?-/?-HPV had a highly significant, independent association with oropharyngeal tumors even in those who tested positive for HPV16. ?-/?-HPV have known associations with skin cancer (SC) in patients with epidermodysplasia veruciformis, and are increasingly thought to play a role SC in general. SC incidence is highly elevated in PLWH and transplant patients (relative to the general population), consistent with an infectious cause. However, the role of ?-/?-HPV in cancer is thought to be distinct from that of HR ?-HPV. While HR ?-HPV are a necessary cause of cervical precancer/cancer, it is likely that ?-/?-HPV are more akin to a carcinogen. Whereas HR ?-HPV are found integrated or episomal in tumor cells, ?-/?-HPV are transient and cannot reliably be detected in tumors. Nonetheless, ?-/?-HPV are common, including in the oral cavity, cervicovaginal and anal specimens, and ?-/?-HPV prevalence increases with HIV and low CD4. To our knowledge, however, there have been no longitudinal studies to understand the natural history of cervical ?-/?-HPV in HIV[+] or HIV[-] women. More importantly, there have been no prospective studies of ?-/?-HPV and subsequent cervical pre-cancer/cancer. Prospective/longitudial studies are essential since, as mentioned, ?-/? HPV are transient and the virus may not be concurrent with cervical disease. We therefore propose studying ?-/?-HPV natural history and it?s relation with cervical precancer/cancer in the Women?s Interagency HIV Study (WIHS). Few if any other cohorts have the needed long-term follow-up with q6mo gynecological exams, Pap testing and colposcopy/biopsy (when indicated).