Comparison of HPV Antibodies Measured Prior to Diagnosis of Anal, Cervical, Oropharyngeal, Penile and Vaginal Cancers in the HPV Cancer Cohort Consortium

Antibodies against HPV proteins can provide pre-diagnostic information about cancer development. We described the prevalence of antibodies to proteins of oncogenic HPV types prior to diagnosis of HPV-related cancers. We analysed pre-diagnostic blood from 1700 participants with incident HPV-related cancers (anal = 387, cervical = 274, oropharyngeal = 788, penile = 168, vaginal = 83) and 6221 controls from nine prospective cohorts in Europe, North America and Australia in the HPV Cancer Cohort Consortium. We measured antibodies against E6, E7 and L1 proteins for 6 HPV types, and additionally against E1, E2, E4, E6, E7 and L1 proteins of HPV16 and 18. We described seroprevalence by lead time from blood draw to cancer diagnosis (range: 0-43 years). We found that among oropharyngeal cancers, seroprevalence increased approaching diagnosis for HPV16 E1, E2, E4, E6, E7, L1 and HPV18 E1, E2, L1 (HPV16-E6: from 10.4% at > 20 years to 35.8% at 0-5 years, vs. 0.3% in controls). Anal cancer showed similar patterns for HPV16 E1, E2, E4, E6 and L1 and HPV18 E2 (HPV16-E6: from 3.8% at > 20 years to 29.8% at 0-5 years). No trends were observed for cervical, penile, or vaginal cancers. In a multivariable model fit among cases, HPV16-E6 seropositivity was higher at shorter lead times and more recent calendar periods, lower among US non-Hispanic Blacks, and varied by cancer type (highest in oropharyngeal followed by anal, vaginal, penile and cervical) (all p < 0.03). In conclusion, pre-diagnostic HPV antibody responses vary by cancer type, with seroprevalence of 6-9 HPV proteins increasing approaching diagnosis for oropharyngeal and anal cancers, but not cervical, penile or vaginal cancers.