Oral human papillomavirus infection before and after treatment for human papillomavirus 16-positive and human papillomavirus 16-negative head and neck squamous cell carcinoma

Abstract

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.

Figure One. Type-specific detection of oral HPV infection (other than HPV16) before and after therapy in patients with HPV16-positive and HPV16-negative HNSCC

All oral HPV infections, other than type HPV16, detected during the study are shown in the figure. Data from each case (indicated by case number in the column “subject”) is delineated by horizontal gray lines. Subjects with HPV16-positive and HPV16-negative HNSCC are above and below the black horizontal line, respectively. Each row indicates a separate, type-specific infection, specified in the column labeled “HPV type.” Oral rinse samples (ORS) that were β-globin positive and therefore evaluable are represented by circles: solid black and open circles represent HPV-positive and HPV-negative ORS, respectively. β-globin negative samples are represented by an “X.” Time points for oral rinse collection relative to the start of cancer therapy are indicated on the X-axis in days. Two patients had samples that predated start of treatment by an extended period of time because of temporary loss to follow-up (subject 95) or because of a prior diagnosis of a metasynchronous head and neck cancer (subject 6). * Not shown are three HPV-negative oral rinse samples from subject 96 collected at days 2348, 2576, 2665 post treatment start.