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HPV-related oropharyngeal cancer incidence increasing among older adults

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July 20, 2018

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.

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.

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Perspective

The retrospective series published by Windon and colleagues provides a detailed analysis of the evolving demographic landscape for HPV-positive oropharynx cancer. In particular, they have effectively demonstrated the increasing median age of cohorts at two tertiary care centers from 1995 to 2013. Etiologic factors to explain this trend have yet to be studied.

The authors highlighted limitations of their study, including the lack of treatment data and the need to look at larger series that may be more generalizable to an overall U.S. population. Both centers in this analysis are based in urban centers, which may impact the patient referral patterns. The observed lower magnitude of OS benefit among the oldest group of patients could be related to multiple factors, such as the competing morbidities in this population, inability to receive treatment due to performance status and the decreased ability to tolerate toxicities, as well as the increased potential for intrinsic immunosuppression. During the latter part of this time frame, many older patients have been treated with cetuximab (Erbitux, Eli Lilly) and radiation instead of cisplatin.

As data from RTOG 1016 are emerging, it is possible that this treatment can be associated with inferior survival. The age range in the oldest group was not listed and, as more octogenarians are presenting to oncology clinics, it is essential that we consider both acute and long-term toxicities while discussing goals of care and prognosis during the initial decision-making. Thus, the increased incidence of HPV-positive oropharynx cancer among older patients requires further study to obtain greater understanding of the ongoing changes in epidemiology and treatment patterns.

Ranee Mehra, MD

HemOnc Today Editorial Board Member
Johns Hopkins Medicine

Disclosure: Mehra reports a consulting role with Genentech and researcher funding from Astra Zeneca.