Longitudinale Biomarkeranalysen in serologiebasiertem Screening auf HPV-induzierte Oropharynxkarzinome

Introduction:An increasing proportion of oropharyngeal cancers are caused by HPV (HPV-OPC) and serum antibodies against HPV16 early antigens(EA), especially E6, as well as cell-free HPV DNA (cfHPV-DNA) are emerging blood-based markers. We present longitudinal data from a prospective proof-of-concept study of HPV serology-based HPV-OPC screening. Material and Methods:Anti-HPV antibodies were measured in 4,424 sera of the HCHS, a population-based cohort study. Participants seropositive for HPV16 E6 and at least one additional EA were considered at high risk for HPV-OPC and participants positive for E6 alone at low risk. All at-risk participants were invited for bi-annually head and neck examinations(FU) for tumor detection and blood draws. Results:10/12 high risk participants attended FU and 5 developed HPV-OPC. All tumor cases were continuously positive for E6 and E2 antibodies, whereas positivity for E7 and E1 was less consistent. In contrast, only 3/5 and 1/5 non-tumor cases were positive for E6 or a second antigen, respectively. Regarding cfHPV DNA, 4/5 tumor cases were positive at diagnosis. Prediagnostic samples were available for 3 and all demonstrated borderline positivity and a steep increase just prior to diagnosis. Non-tumor cases were all negative, except for a single participant continuously positive for cfHPV DNA and 3 EA antibodies through 5 years of FU, suggesting a far higher risk profile than the other non-tumor cases. The only tumor case in the low-risk group was diagnosed on the first visit and was the only one in this cohort to demonstrate seroconversion to a second antibody and cfHPV DNA positivity. Conclusion:Serology-based screening for HPV-OPC is feasible and longitudinal biomarker assessment may be able to refine the original risk classification.

Die Studie wurde von der Hamburger Krebsgesellschaft unterstützt.