Incidence and Demographic Burden of HPV-Associated Oropharyngeal Head and Neck Cancers in the United States

Abstract

Background: Human papillomavirus (HPV)-positive oropharyngeal head and neck squamous cell carcinoma (OPSCC) is increasing in the United States. Current epidemiologic assessments of the national burden of HPV-positive OPSCC are needed.Methods: The Surveillance Epidemiology and End Results HPV Status Database included 12,017 patients with head and neck squamous cell carcinoma of pharyngeal subsites, including OPSCC and non-OPSCC head and neck cancer subsites (hypopharynx, nasopharynx, and "other pharynx"), diagnosed from 2013 to 2014. Age-adjusted incidence rates per 100,000 persons by HPV status were calculated. An exploratory Fine-Gray competing-risks regression determined the associations between HPV status and cancer-specific mortality.Results: From 2013 to 2014, the U.S. incidence of HPVpositive OPSCC was 4.62 [95% confidence interval (CI), 4.51-4.73] versus 1.82 (95% CI, 1.75-1.89) per 100,000 persons for HPV-negative OPSCC. The incidence of HPV-positive versus negative non-OPSCC of the head and neck was 0.62 (95% CI, 0.58-0.66) versus 1.38 (95% CI, 1.32-1.44). White race (5.47) and male sex (8.00) had the highest incidences of HPV-positive OPSCC, with a unimodal age incidence distribution peaking at ages 60 to 64 years (27.23). HPV positivity was associated with lower cancer-specific mortality than HPV-negative disease for OPSCC [adjusted HR (aHR), 0.40; P < 0.001], but not non-OPSCC (aHR, 1.08; P ¼ 0.81), P interaction ¼ 0.002.Conclusions: The U.S. incidence of HPV-positive OPSCC was 4.62 per 100,000 persons. Most cases were found in white male patients younger than 65 years, where it represents the sixth most common incident nonskin cancer. The favorable prognosis associated with HPV appears to be limited to the oropharynx.Impact: This large population-based epidemiologic assessment of the U.S. population defines the incidence and demographic burden of HPV-positive OPSCC.

Durable therapeutic gain despite competing mortality in long-term follow-up of a randomized hyperfractionated radiotherapy trial for locally advanced head and neck cancer

“…However, smoking pack-year data seems balanced between both arms and the majority (93%) patients were heavy smokers. As well, this trial accrued patients from 1988 to 1995 before the dramatically increased incidence of HPV + OPC which now amounts to 4.62 per 100,000 persons in the U.S. and represents the sixth most common incident non-cutaneous cancer in white males <65 years [43]. The chance of HPV status confounding the oncologic outcomes in this trial is therefore low.…”

<p>Potential of Pembrolizumab in Metastatic or Recurrent Head and Neck Cancer: Evidence to Date</p>

“…Overall, HPVassociated HNSCC of oropharyngeal origin is seen in younger, predominantly white males of higher socioeconomic status (SES). 10,11 Genotypes 16 and 18 are more commonly seen in the United States compared to Europe and Asia, but this is largely due to the fact that HNSCC is primarily non-HPV related in these regions. 12 HPV genotype 16 (p16) accounts for over 90% of cases.…”

“…14 This is reflected in a recent incidence analysis per 100,000 of HPV-positive (4.62, 95% CI=4.51-4.73) versus HPV-negative (1.82, 95% CI=1.75-1.89) HNSCC patients. 11 In HPV-associated disease, HPV promotes carcinogenesis by integrating into the DNA of the host leading to activation of oncoproteins E6 and E7, which in turn dysregulate tumor suppressors TP53 and Rb, respectively. TP53, one of the most important tumor suppressor genes encoding for a transcription factor with roles in DNA repair, cell cycle regulation, apoptosis, and genomic stability is mutated in approximately 80% of HPV-negative cases, as TP53 is degraded by HPV oncoprotein E6 in HPV-positive disease.…”

Awareness of Human Papillomavirus (HPV) Infection among Indigenous Males in North America and Oceania

“…Incidence of HPV-positive head and neck cancer is highest in white males, such as in the United States (Mahal et al, 2019;Stein et al, 2015) and Europe (Stein et al, 2015). An overall, current disbelief of being at low risk to contract HPV infection among Indigenous men may explain the practice of unprotected sex, increasing their risk of developing oropharyngeal, penile, and anal cancer in the future (Hodge, 2014).…”