Associations of Oral α-, β-, and γ-Human Papillomavirus Types With Risk of Incident Head and Neck Cancer

Abstract

IMPORTANCE Prospective studies are needed to examine the temporal relationship between oral human papillomavirus (HPV) detection and risk of head and neck squamous cell carcinoma (HNSCC). Moreover, the oral cavity contains a wide spectrum of α-, β-, and γ- HPV types, but their association with risk of HNSCC is unknown. OBJECTIVE To prospectively examine associations between α-, β-, and γ-HPV detection in the oral cavity and incident HNSCC. DESIGN A nested case-control study was carried out among 96 650 participants, cancer free at baseline, with available mouthwash samples in 2 prospective cohort studies: (1) the American Cancer Society Cancer Prevention Study II Nutrition Cohort and (2) the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Incident cases of HNSCC (n = 132) were identified duringan average 3.9 years of follow-up in both cohorts. Three controls per case (n = 396) were selected through incidence density sampling and matched on age, sex, race/ethnicity, and time since mouthwash collection. METHODS Through a next-generation sequencing assay, DNA from α-, β-, and γ-HPV types were detected. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% CIs, adjusting for smoking history, alcohol consumption, and detection of HPV-16 for β- and γ-HPVs. MAIN OUTCOMES AND MEASURES Incident HNSCC, which includes cancers of the oropharynx, oral cavity, and larynx. RESULTS A total of 132 participants developed HNSCC during the follow-up period (103 men and 29 women; average age at baseline, 66.5 years). Oral HPV-16 detection was associated with incident HNSCC (OR, 7.1; 95% CI, 2.2–22.6), with positive association for oropharyngeal SCC (OR, 22.4; 95% CI, 1.8–276.7), but not for oral cavity (OR, 4.5; 95% CI, 0.6–34.7) or laryngeal SCCs (OR, 0.11; 95% CI, 0.01–834.80). Detection of β1-HPV-5 and β2-HPV-38 types, as well as γ-11 and γ-12 species, had ORs for HNSCC that ranged from 2.64 to 5.45 (P < .01 for all comparisons). Detection of β1-HPV-5 type was associated with oropharyngeal (OR, 7.42; 95% CI, 0.98–56.82; P = .054), oral cavity (OR, 5.34; 95% CI, 1.51–18.80; P = .01), and laryngeal SCCs (OR, 2.71; 95% CI, 1.00–7.43; P = .05), whereas γ11- and γ12-HPV species were associated with both oral cavity (OR, 7.47; 95% CI, 1.21–46.17; P = .03; and OR, 6.71; 95% CI, 1.47–30.75; P = .01, respectively) and laryngeal SCCs (OR, 7.49; 95% CI, 1.10–51.04; P = .04 and OR, 5.31; 95% CI, 1.13–24.95; P = .03, respectively). CONCLUSIONS AND RELEVANCE This study demonstrates that HPV-16 detection precedes the incidence of oropharyngeal SCC. Associations of other HPVs, including γ11- and γ12-HPV species and β1-HPV-5 type suggest a broader role for HPVs in HNSCC etiology.

Oral HPV prevalence in general healthy dental patients and patients with oral and oropharyngeal neoplasms in Bulgaria

“…The discovery of HPV16 precedes the onset of oropharyngeal cancer. Binding to other HPV types including γ11-and γ12-HPV and β1-HPV-5 type suggest a broader role for HPV in the aetiology of squamous cell carcinomas in the maxillofacial area (12). In this respect, our results are close to this idea.…”

Diversity of beta-papillomavirus at anogenital and oral anatomic sites of men: The HIM Study

“…We and others have recently described the high prevalence and diversity of β-HPVs at non-cutaneous anatomic sites 14–19 . The purpose of this study was to describe the prevalence of 43 β-HPV types among samples collected at the same time point from the external genital skin, the anal canal, and oral cavity from men enrolled in the multinational HPV Infection in Men (HIM) cohort study.…”

NCCN Guidelines Insights: Head and Neck Cancers, Version 2.2017

“…3 HPV is now well accepted as a cause of squamous cancers of the oropharynx (particularly cancers of the tonsils and tongue base). [4][5][6][7][8][9][10][11] The overall incidence of HPV-positive H&N cancers is increasing in the United States, whereas the incidence of HPV-negative (primarily tobacco-and alcohol-caused) cancer is decreasing. 12 Patients with HPV-associated H&N cancer tend to be younger.…”

“…12,[14][15][16][17] Oral HPV type 16 (HPV16) infection increases the risk of oropharyngeal cancer 4,10,18,19 and a strong causal relationship has been established 4,18 ; HPV types 18, 31, and 33 are responsible for the vast majority of the remaining fraction. 11 Expression of HPV E6 and E7 oncogenes inactivates the tumorsuppressor proteins p53 and pRb, respectively, which leads to the development of cancer.…”