Antibodies to HPV16 are strongly associated with head and neck squamous cell carcinoma (HNSCC), particularly oropharyngeal cancer (OPC). The presentation will summarize published and ongoing case-control and prospective cohort studies using multiplex serology.
Antibodies to HPV16 L1, E1, E2, E4, E6, and E7 proteins in serum or plasma samples were analyzed by Luminex-based multiplex serology. Tumor HPV status was determined by HPV in-situ hybridization (ISH), HPV DNA detection, HPV RNA patterns (E6*I, E1^E4 and E1C), and p16 immunohistochemistry (IHC).
In multiple studies, antibodies to HPV16 E6 were shown to be the serological marker most strongly associated with OPC. They were almost exclusively present in cases with molecularly defined HPV-driven OPC, yielding a sensitivity and specificity compared to tumor HPV status exceeding 90% and 95%, respectively. The prevalence of HPV16 E6 antibodies in healthy controls has been repeatedly shown to be in the range of 0.5%, i.e. the disease specificity of this biomarker exceeds 99%. Antibodies to other HPV16 serological markers, especially E1, E2 and E7, were also associated with OPC, albeit less strongly, based on higher prevalence among controls and/or lower prevalence in OPC cases.
HPV 16 serological markers, especially antibodies to E6, have been repeatedly shown in both case-control and prospective cohort studies to be highly specific biomarkers for detection and prediction of OPC. To date, the trigger for seroconversion (e.g., yet to be described premalignant OPC lesions) is not understood, and the clinical implications of early HPV-OPC detection are under debate.