A Tale of Two Viruses: HPV Infection and Associated Anal Dysplasia among Hawai‘i HIV-Seropositive Patients and Related HIV-Seroconversion Risk in a Thai Population

Abstract

Human immunodeficiency virus (HIV) and human papillomavirus (HPV) are both sexually transmitted pathogens. As the most prevalent sexually transmitted infection in the world, HPV affects both men and women across many demographic categories. Although HPV often clears without treatment, persistent infection can cause dysplasia which can progress to cancer. HPV vaccines, licensed in the US since 2006, hold promise for reducing not only infection rates but also incidence of HPV-associated cancers. Albeit less prevalent than HPV, HIV still represents a considerable health burden worldwide even in an era of effective combination anti-retroviral therapy (cART). In the US, the majority of new HIV cases arise among gay and bisexual men. Despite billions of dollars and years devoted to research, an effective HIV vaccine remains elusive. Since HIV-positive individuals are more susceptible to other infections even while on anti-retroviral therapy, they are also prone to HPV infection and associated anal dysplasia. Additionally, a growing body of evidence suggests that HPV also impacts the acquisition of HIV. The axes of interactions between these two viral infections are not yet fully understood. The overall objective of this study was to further elucidate the relationship between HIV and HPV infection in anal dysplasia/cancer by assessing HPV infection in the context of HIV and vice versa. The central hypotheses were that HIV-positive individuals present more frequently with HPV infection and associated anal dysplasia and that HIV seroconversion may occur subsequent to HPV infection. First, the study demonstrated that HPV at non-anal sites may be associated with anal dysplasia/cancer among HIV-positive males. The presence of HPV and the number of HPV genotypes at anatomical sites other than the anus trended toward higher odds of ASIL. Presence of HPV and the number of HPV genotypes at the penile shaft conferred the highest, statistically significant odds of ASIL – greater odds than conferred by presence of HPV and the number of HPV genotypes at the anus itself. Second, the study showed the potential of HPV quantitation for enhanced screening and diagnosis of anal dysplasia/cancer in the context of HIV infection. All participants with HGAIN had HPV-16 E6 DNA levels above 10 copies per cell. Participants with LGAIN or Negative biopsy results and low HPV-16 E6 copy could potentially have avoided invasive HRA if HPV quantitation were used as a supplemental diagnostic marker for anal dysplasia. Third, the study explored the effect of prior HPV infection on acquisition of HIV. Among MSM and TG women in the Thai Test & Treat cohort, HPV acquisition appeared to increase the risk of subsequent HIV seroconversion. Despite remaining ambiguity over HPV’s role in HIV acquisition, some researchers are advocating for study of HPV vaccination as a means for reducing HIV incidence. This study has contributed to the body of knowledge in the field by identifying new diagnostic indicators of HPV-associated anal dysplasia and by providing additional evidence for HPV’s influence on HIV acquisition. Further investigation will permit validation of these novel diagnostic markers and innovative strategy for reducing the global incidence of HIV.