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July 20, 2018
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HPV-related oropharyngeal cancer incidence increasing among older adults

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The median age of patients with HPV-related oropharyngeal squamous cell carcinoma increased since 1995, reflecting the increasing incidence among older adults, according to results of a retrospective study.

Perspective from

Regardless of age, patients with HPV-related oropharyngeal squamous cell carcinoma demonstrated improved OS compared with patients with HPV-unrelated tumors.

“Past research has shown that patients with HPV-positive oropharyngeal squamous cell carcinoma have a lower median age at diagnosis than patients with HPV-negative oropharyngeal squamous cell carcinoma,” Melina J. Windon, MD, postgraduate resident in the department of otolaryngology and head and neck surgery at Johns Hopkins, and colleagues wrote. “Indeed, earlier studies showed that the median age at oropharyngeal squamous cell carcinoma diagnosis decreased during 1973-2004 and 1977-2012, likely because of the growing proportion of HPV-positive oropharyngeal squamous cell carcinomas. However, a population-based study reported an increase in oropharyngeal squamous cell carcinoma incidence among adults 65 years or older in the United States between 2000 to 2012, and there was a concomitant decrease in nonoropharyngeal head and neck cancer among adults of the same age. This suggests that the increase in oropharyngeal squamous cell carcinoma incidence among older adults may be driven by HPV, although this has not been well studied.”

Windon and colleagues conducted a retrospective study of 239 patients (men, 67%) with oropharyngeal squamous cell carcinoma diagnosed from 1995 to 2013. Researchers divided patients into three age groups: younger adults aged 18 to 54 years (n – 98), middle-aged adults aged 55 to 64 years (n = 83) and older adults aged 65 years or older (n = 58).

The researchers performed p16 immunohistochemistry and in situ hybridization for HPV-16, high-risk DNA and/or E6/E7 RNA.

Sixty percent of patients were p16 positive.

The proportion of patients with p16-positive tumors increased over the study period for all age groups — from 50% to 70% among younger patients, 24% to 77% among middle-aged patients (P for trend < .001), and from 41% to 75% among older patients (P for trend = .04).

From 1999 to 2013, the median age increased among p16-positive patients from 53 to 58 years (P for trend = .01), but not among p16-negative patients.

Median follow-up was 3.5 years

Across all age groups, a greater proportion of patients with p16-positive tumor status achieved 5-year OS than patients with p16-negative tumors (77% vs. 40%; P < .001).

After adjustment for other factors, p16 status was associated with improved survival (HR = 0.31; 95% CI, 0.19-0.51). Researchers observed this association among younger adults (HR = 0.31; 95% CI, 0.13-0.73) and middle-aged adults (HR = 0.09; 95% CI, 0.01-0.6), but not significantly among older adults (HR = 0.46; 95% CI, 0.17-1.27).

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“This is the first study to demonstrate that the observed rise in oropharyngeal squamous cell carcinoma among older adults is driven by an increased prevalence of p16-positive tumors, and this indicates that HPV-positive oropharyngeal squamous cell carcinoma is no longer a disease of young individuals,” the researchers wrote. “Notably, the age at diagnosis of patients with HPV-positive oropharyngeal squamous cell carcinoma has increased in recent years, and HPV remains a biomarker of improved prognosis among older patients.”

Limitations of the study included the retrospective nature, the potentially decreased ability to generalize trends to the U.S. population, and the absence of treatment data and disease-specific survival.

In an accompanying editorial, Anil K. Chaturvedi, PhD, of the NCI, and Zachary S. Zumsteg, MD, of Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, expressed an “urgent need” for trials focusing on adults with head and neck cancers who are aged older than 65 or 70 years.

“There is no high-level evidence to guide therapeutic decisions for this population because older patients have historically been underrepresented in clinical trials or excluded altogether,” they wrote. – by Cassie Homer

Disclosures: Windon reports no relevant financial disclosures. One author reports consultant/advisory roles with Medtronic and Olympus. Chaturvedi reports no relevant financial disclosures. Zumsteg reports consultant/advisory board roles with EMD Serono and Scripps Proton Therapy Center.