Antibodies against HPV16E6 oncoprotein in the Swiss HIV Cohort Study: kinetics and anal cancer risk prediction.

Combes, Jean-Damien; Clifford, Gary M; Günthard, Huldrych F; Hauser, Christoph; Darling, Katharine E A; Valladares, Pablo; Battegay, Manuel; Waldeck, Frederike; Bernasconi, Enos; Bertisch, Barbara; Hirsch, Hans H; Brenner, Nicole; Waterboer, Tim; Scherrer, Alexandra U (2020). Antibodies against HPV16E6 oncoprotein in the Swiss HIV Cohort Study: kinetics and anal cancer risk prediction. International journal of cancer, 147(3), pp. 757-765. Wiley-Blackwell 10.1002/ijc.32784

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Our aim was to describe HPV16E6 antibody kinetics prior to anal cancer in people living with HIV/AIDS (PLWHA) and evaluate the possible contribution of HPV16E6 serology to anal cancer risk prediction. For 91 persons diagnosed with anal cancer in the Swiss HIV Cohort Study (1989-2017), serial serum/plasma samples were tested for HPV16E6 antibodies using multiplex serology, supplemented with samples from 1,356 participants without anal cancer. Anal cancer incidence was estimated for PLWHA from 40 years-old in the cART era, stratified by HPV16E6 serostatus. HPV16E6 seroprevalence was 23.3% in samples <2 years prior to anal cancer diagnosis and decreased with increasing time prior to cancer: 16.7% at 2-4 years, 4.4% at 5-9, and 7.0% at >10 years. Of 25 individuals with anal cancer who were HPV16E6-seropositive at any time during follow-up, the majority (n=18) remained seropositive in all samples following seroconversion, whereas for 7 cases, seropositivity was transitory. Among individuals with anal cancer, HPV16E6 seroprevalence was marginally higher in women versus men who have sex with men (adjusted OR=4.3, 95% CI: 1.1, 17.2) and in older participants (adjusted OR=6.2, 95% CI: 1.1, 34.8 for cases diagnosed at ≥55 versus <45 years). Anal cancer incidence was 402/100,000 person-years in HPV16E6-positive versus 82/100,000 in HPV16E6-negative PLWHA (incidence rate ratio=4.9, 95% CI: 1.3, 13.1). In conclusion, HPV16E6 serology, despite its low sensitivity, allows characterization of a group of individuals with very high anal cancer incidence and may have a place in secondary prevention in groups at high risk for anal cancer such as PLWHA. This article is protected by copyright. All rights reserved.

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