Risk of Oropharyngeal Cancer After a Positive HPV16-E6 Serology Test

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In an analysis from the Human Papillomavirus Cancer Cohort Consortium (HPVC3) reported in the Journal of Clinical Oncology, Robbins et al found substantial risks of oropharyngeal cancer over time among persons, particularly males, with positive results on human papillomavirus (HPV) 16-E6 serologic testing.

Study Details

The investigators constructed an oropharyngeal cancer risk prediction model integrating relative odds of oropharyngeal cancer for HPV16-E6 serostatus and cigarette smoking from the HPVC3, U.S. population risk factor data from the National Health Interview Survey, and U.S. sex-specific population rates of oropharyngeal cancer and mortality. The study included 365 participants with oropharyngeal cancer (243 men and 122 women) with up to 10 years between blood draw and diagnosis and 5,794 controls (3,600 men and 2,194 women) from nine cohort studies in the United States, Europe, and Australia in which blood samples were collected between 1972 and 2009.  

Key Findings

Among HPV16-E6 seropositive women, the estimated 10-year risk of oropharyngeal cancer was 3.6% (95% confidence interval [CI] = 2.5%–5.9%) at age 50 and 5.5% (95% CI = 3.8%–9.2%) at age 60. Estimated 5-year risks were 1.5% at age 50 and 2.7% at age 60.  

Among seropositive men, the estimated 10-year risk of oropharyngeal cancer was 17.4% (95% CI = 12.4%–28.6%) at age 50 years and 27.1% (95% CI = 19.2%–45.4%) at age 60 years. Estimated 5-year risks were 7.3% at age 50 and 14.4% at age 60. It was estimated that after a seropositive result at age 50 years, 49.9% of men and 13.3% of women would develop oropharyngeal cancer over 30 years.

Among HPV16-E6 seronegative persons, estimated 10-year risks of oropharyngeal cancer were very low, ranging from 0.009% to 0.25% according to age, sex, and smoking status. Among ever-smokers, 10-year risks were 0.03% at age 50 and 0.05% at age 60 among women and 0.15% and 0.25%, respectively, among men. Among never-smokers, 10-year risks were 0.009% at age 50 and 0.014% at age 60 among women and 0.05% and 0.08%, respectively, among men.

The investigators concluded, “We estimate that a substantial proportion of HPV16-E6 seropositive individuals will develop oropharyngeal cancer, with 10-year risks of 17% to 27% for males and 4% to 6% for females age 50 to 60 years…. This high level of risk may warrant periodic, minimally invasive surveillance after a positive HPV16-E6 serology test, particularly for males in high-incidence regions. However, an appropriate clinical protocol for surveillance remains to be established.”

Hilary A. Robbins, PhD, of the Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC), Lyon, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the U.S. National Cancer Institute and others. For full disclosures of the study authors, visit

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