The risk of head and neck squamous cell carcinoma (HNSCC) associated with common human
papillomavirus types has not been well defined.
We conducted a case-control study of 1034 individuals (486 incident cases diagnosed
with HNSCC and 548 population-based controls matched to cases by age, gender, and
town of residence) in Greater Boston, MA. Sera were tested for antibodies to human
papillomavirus (HPV)6, HPV11, HPV16, and HPV18 L1.
HPV6 antibodies were associated with an increased risk of pharyngeal cancer [odds
ratio (OR)=1.6, 1.0-2.5], controlling for smoking, drinking, and HPV16 seropositivity.
In HPV16-seronegative subjects, high HPV6 titer was associated with an increased risk
of pharyngeal cancer (OR=2.3, 1.1-4.8) and oral cancer (OR=1.9, 1.0-3.6), suggesting
that the cancer risk associated with HPV6 is independent of HPV16. There was no association
between smoking and alcohol use and HPV6 serostatus. Further, the risk of pharyngeal
cancer associated with heavy smoking was different among HPV6-seronegative (OR 3.1,
2.0-4.8) and HPV6-seropositive subjects (OR=1.6, 0.7-3.5), while heavy drinking also
appears to confer differing risk among HPV6-negative (OR 2.3, 1.5-3.7) and -positive
subjects (OR=1.3, 0.6-2.9).
There may be interactions between positive serology and drinking and smoking, suggesting
that the pathogenesis of human papillomavirus in HNSCC involves complex interactions
with tobacco and alcohol exposure.