Human papillomavirus seropositivity and risks of head and neck cancer

Abstract

We examined antibody response to VLP HPV‐16, HPV‐16 E6 and E7 antibodies as potential seromarkers of HPV‐related head and neck cancer (HNC). The study included 204 HNC cases and 326 controls evaluated for HPV presence in sera using ELISAs for anti‐HPV VLP antibodies and HPV‐16 E6 and/or E7 antibodies, and in tumor tissue using PCR and DNA sequencing. Anti‐HPV‐16 VLP was detected in 33.8% of cases and 22.4% of controls, anti‐E6 in 20.6% of cases and 0.9% of controls and anti‐E7 in 18.6% of cases and 0.6% of controls. HPV‐16 DNA was detected in 26.1% of tumors. The adjusted risk of HNC was elevated among those seropositive for HPV‐16 VLP (odds ratio (OR) = 1.7, 1.1–2.5), E6 (OR = 32.8, 9.7–110.8) or E7 (OR = 37.5, 8.7–161.2). Compared to HPV DNA‐negative/seronegative cases, tumor HPV‐16 cases had increased risk of detection with anti‐VLP antibodies (OR = 6.8, 3.1–14.9). The odds were more pronounced among cases seropositive for E6 (OR = 69.0, 19.3–247) or E7 (OR = 50.1, 14.7–171). Antibodies against E6 or E7 were associated with risk of cancer in the oral cavity (OR = 5.1, 1.2–22.4) and oropharynx (OR = 72.8, 16.0–330), and with disease characteristics: stage, grade and nodal status. Anti‐E6 and/or E7 antibodies were found in 74% of tumor HPV‐16 positive cases but in only 5% of tumor HPV‐negative cases (K =0.7, 0.6–0.8) suggesting good correlation between the serologic marker and HPV tumor status. Antibodies to HPV‐16 E6 and/or E7 represent a more specific biomarker than anti‐HPV‐16 VLP of an HPV‐related HNC. Because of the survival advantage of HPV‐related HNC, HPV‐16 E6/E7 detection may be useful in therapy targeted for HPV‐related tumors.