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Oral Human Papillomavirus Infection Before and After Treatment for Human Papillomavirus 16–Positive and Human Papillomavirus 16–Negative Head and Neck Squamous Cell Carcinoma

Authors' Affiliations: Departments of ¹ Otolaryngology-Head and Neck Surgery, ² Pathology, Johns Hopkins Hospital, and ³ Division of Viral Oncology, Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, Maryland; and ⁴ Basic Research Laboratory, National Cancer Institute, Frederick, Maryland

Requests for reprints: Maura L. Gillison, Johns Hopkins University, Cancer Research Building 1, Rm 351, 1650 Orleans Street, Baltimore, MD 21231. Phone: 410-502-7412; Fax: 410-955-0840; E-mail: gillima{at}jhmi.edu.

Purpose: Oral human papillomavirus (HPV) infection is a risk factor for head and neck squamous cell carcinoma (HNSCC), and is a concern for patients with HPV-positive HNSCC and their partners. The prevalence of oral HPV infection before and after cancer therapy was investigated among patients with HPV16-positive and HPV16-negative HNSCC.

Experimental Design: Serial oral rinse samples (ORS) were collected from a cohort of 135 HNSCC cases as frequently as every 3 months for up to 3 years. Tumor HPV status was determined by HPV16 in situ hybridization. HPV was detected in ORS by consensus PCR and line blot hybridization. The HPV16 variants in positive oral rinse–tumor pairs were determined by sequencing. The odds of oral HPV infection among HPV16-positive and HPV16-negative cases were compared by use of generalized estimating equations.

Results: Patients were followed for a median of 21 months and provided a median of 4 samples. Forty-four of 135 patients had HPV16-positive tumors. HPV16-positive cases were more likely than HPV16-negative cases to have an oral HPV infection detected before (odds ratio, 8.6; 95% confidence interval, 3.5-21) and after therapy (OR, 2.9; 95% confidence interval, 1.1-7.4). Oral infections by HPV16 and other high-risk, but not low-risk, types were more common among HPV16-positive cases both before and after therapy. Most HPV16 variants in ORS were European, unique, and identical to that in the tumor. Persistence of a type-specific oral infection was demonstrable for as long as 5 years.

Conclusion: Oral high-risk HPV infections are more frequent among patients with HPV16-positive than HPV16-negative HNSCC, consistent with a behavioral and/or biological disposition to infection.

Commentary

Genetic Screening for Oral Human Papillomavirus Infections and Cancers of the Head and Neck

John C. Sok and Jennifer R. Grandis
Clin. Cancer Res. 2008 14: 6723-6724. [Abstract] [Full Text] [PDF]