Antibodies against HPV16E6 oncoprotein in the Swiss HIV Cohort Study: kinetics and anal cancer risk prediction. International Journal of Cancer
Combes et al. aimed to describe human papilloma virus (HPV-) 16E6 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 after seroconversion, whereas for seven cases, seropositivity was transitory. Among individuals with anal cancer, HPV16E6 seroprevalence was marginally higher in women vs. 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 vs.<45 years). Anal cancer incidence was 402/100,000 person-years in HPV16E6-positive vs. 82/100,000 in HPV16E6-negative PLWHA (incidence rate ratio = 4.9, 95%CI:1.3, 13.1).
In conclusion, in this first study of HPV16E6 antibodies in serial blood samples collected in PLWHA prior to anal cancer, HPV16E6 was shown to be a strong and specific determinant of future anal cancer risk and may have a place in secondary prevention algorithms in high-risk groups such as PLWHA. One out of every 30 HPV16E6-seropositive PLWHA (n = 4/114) developed anal cancer during their subsequent follow-up, highlighting the positive predictive value of this marker. Conversely, however, the vast majority of anal cancers diagnosed in PLWHA were HPV16E6-negative at study baseline and less than a quarter of PLWHA had seroconverted to HPV16E6 prior to anal cancer diagnosis, meaning that the negative predictive value of a single HPV16E6 test was poor.