Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer

Abstract

Purpose: Human papillomavirus type 16 (HPV16) infection is causing an increasing number of oropharyngeal cancers in the United States and Europe. The aim of our study was to investigate whether HPV antibodies are associated with head and neck cancer risk when measured in prediagnostic sera.

Methods: We identified 638 participants with incident head and neck cancers (patients; 180 oral cancers, 135 oropharynx cancers, and 247 hypopharynx/larynx cancers) and 300 patients with esophageal cancers as well as 1,599 comparable controls from within the European Prospective Investigation Into Cancer and Nutrition cohort. Prediagnostic plasma samples from patients (collected, on average, 6 years before diagnosis) and control participants were analyzed for antibodies against multiple proteins of HPV16 as well as HPV6, HPV11, HPV18, HPV31, HPV33, HPV45, and HPV52. Odds ratios (ORs) of cancer and 95% CIs were calculated, adjusting for potential confounders. All-cause mortality was evaluated among patients using Cox proportional hazards regression.

Results: HPV16 E6 seropositivity was present in prediagnostic samples for 34.8% of patients with oropharyngeal cancer and 0.6% of controls (OR, 274; 95% CI, 110 to 681) but was not associated with other cancer sites. The increased risk of oropharyngeal cancer among HPV16 E6 seropositive participants was independent of time between blood collection and diagnosis and was observed more than 10 years before diagnosis. The all-cause mortality ratio among patients with oropharyngeal cancer was 0.30 (95% CI, 0.13 to 0.67), for patients who were HPV16 E6 seropositive compared with seronegative.

Conclusion: HPV16 E6 seropositivity was present more than 10 years before diagnosis of oropharyngeal cancers.

Fig 1.

Proportion of human papillomavirus type 16 (HPV16) E6 seropositive patients with oropharyngeal (OP) cancer and corresponding odds ratios by lead time from blood draw to cancer diagnosis. Blue bars indicate the proportion of patients with OP cancer who were HPV16 E6 seropositive. Black lines indicate risk of OP cancer by HPV16 E6 serostatus using polytomous logistic regression after adjustment for age at enrollment, sex, country, and tobacco and alcohol use. Numbers at the bottom of the figure indicate how many patients with OP cancer in each time interval.

Fig 2.

Cumulative survival of all-cause mortality among patients diagnosed with oropharyngeal cancer by prediagnostic human papillomavirus type 16 (HPV16) E6 serostatus. Patients who were seropositive (blue line; n = 47) and seronegative (gold line; n = 88) for HPV16 were compared for all-cause mortality. Numbers at the bottom of the figure indicate number of patients at the start of each time interval by HPV16 E6 serostatus.