Current Organisation

Wits Reproductive and HIV Research Institute, University of the Witwatersrand

Current Job Title

Senior Research Clinician

Biography

Publications

Project Title

The epidemiology of HPV infection and related disease among HIV infected men in South Africa (TEHSA)

EDCTP Project Call

Career Development Fellowship (CDF)

Host Organisation

Project Objectives

Aim: generate further evidence regarding the epidemiology and burden of disease associated with HPV infection in HIV positive men, in order to inform future prevention policies in South Africa (SA). Specific Objectives: 1) Describe and report the epidemiology of anogenital and oropharyngeal cancer patterns and trends in men including incidence and mortality rates and differences by ethnicity in SA between 1994 and 2010. Furthermore, the influence of HIV status on epidemiology of these cancers will be explored. 2) Determine the prevalence of anogenital and oropharyngeal HPV infection, genotype distribution, and associations with anogenital disease, according to HIV-related factors (e.g. plasma viral load, CD4+ counts) and exposure to antiretroviral treatment (ART). a) Within this, compare the performance of oral swabs to oral rinses in detecting oral HPV infection in an urban cohort of HIV positive men in SA. 3) Determine the incidence, persistence, and clearance of type-specific anogenital and oropharyngeal HPV infection and anal cytological lesions over 18 months and the effects of HIV-related factors and ART on these outcomes. a) Within this, determine the clinical relevance of HPV viral load to predict persistence of infection and cytological abnormalities at follow-up and effects of HIV-related factors on these outcomes.

Study Design

Multi-design: (i) Review of the pathology based cancer reports from the South Africa National Cancer Registry (NCR) and mortality statistics from Statistics South Africa from 1994 to 2013 (ii) A 18 months observational cohort of 304 HIV-infected men from Johannesburg.

Project Summary

Globally, the incidence of human papillomavirus (HPV) associated anal and oropharyngeal cancers (OPCs) in men are increasing. Anogenital warts (AGWs) cause significant morbidity in men and result in high medical costs worldwide. Fewer data exist for men in Sub-Saharan Africa (SSA) including South Africa (SA) due to paucity of research and poor quality cancer registries. Thus quantification of the burden of disease in SSA is of significant importance. There is enough data suggesting that HPV infection is a primary underlying cause of AGWs and these cancers. Available data from other settings suggests that HIV alters the susceptibility and the natural history of HPV-associated diseases, leading to higher rates of pre-cancerous lesions. Studies suggest that antiretroviral therapy (ART) increases the regression of Cervical Intraepithelial Neoplasia (CIN) lesions, indicating immune reconstitution; however the incidences for Anal Intraepithelial Neoplasia (AIN) and oropharyngeal lesions seem continuously increase despite ART initiation. It is therefore important to additionally understand the natural history of anogenital and oral HPV infection in HIV positive men and factors associated with HPV disease progression. Screening programmes for AIN are not widely available due to high costs of high resolution anoscopy which is required to obtain anal biopsies and their benefits in SSA setting are unclear as some of the lesions regress spontaneously. Biomarkers such as HPV viral load to identify men at high risk of progression to cancer are important but require further investigation. HPV DNA testing could be used to screen for OPCs, however the best sampling method for oropharyngeal HPV DNA infection is yet to be agreed on. The work we intend to carryout will answer the following objectives (i) describe and report on the epidemiology of anogenital and oropharyngeal cancer patterns and trends in men including incidence and mortality rates and differences by ethnicity in SA between 1994 and 2010. Furthermore, explore the influence of HIV status on epidemiology of these cancers, (ii) determine the prevalence of anogenital and oropharyngeal HPV infection, genotype distribution and associations with anogenital disease, according to HIV-related factors and exposure to antiretroviral treatment (ART) and (iii) determine the incidence, persistence, and clearance of type-specific anogenital and oropharyngeal HPV infection and anal cytological lesions over 18 months and the effects of HIV related factors and concomitant exposure to ART on these outcom