A Hidden Epidemic of “Intermediate Risk” Oropharynx Cancer

Abstract

ObjectivesOropharyngeal squamous cell carcinoma (OPSCC) incidence is rapidly increasing in the United States and around the world, driven in large part by infection with the human papillomavirus (HPV). HPV associated OPSCC (HPV+OPSCC) has been shown to have improved response to treatment relative to tobacco‐associated OPSCC. However, improvement in patient survival has not been uniform. Subsets of OPSCC patients in the US and around the world continue to have poor oncologic outcomes. Although the drivers of this phenomenon remain unclear, there is increasing evidence that tobacco exposure plays an important role in modulating HPV+OPSCC clinical outcomes.MethodsWe conducted a review of the literature.ResultsWe discuss the potential biological and epidemiological interplay between tobacco and HPV exposure in the context of OPSCC. Multiple retrospective and prospective cohorts show that HPV+OPSCC patients with a history of tobacco exposure have response to treatment and clinical outcomes distinct from HPV+OPSCC non‐smokers which poses clinical and scientific challenges to be addressed over the next decade.ConclusionsThe interaction between tobacco exposure and HPV infection in the context of OPSCC has significant implications for both standard of care treatment regimens and development of novel therapeutic approaches, in particular those which incorporate immunomodulatory agents.Level of Evidence5

CD8 infiltration is associated with disease control and tobacco exposure in intermediate-risk oropharyngeal cancer

“…Modern day oncologic outcomes for HPV+ OPSCC are remarkable, considering the relative lack of clinical progress in other HNSCC disease sites 26,27 . Unlike other sites in which survival has remained relatively flat over the last 2-3 decades (oral cavity) or even decreased (larynx), survival for patients with OPSCC continues to improve, driven primarily by a shift in the epidemiology of the disease toward HPV mediated cancers 2 this shift in survival outcomes for patients with OPSCC has been largely uneven across different segments of the US population 12,30 . One prime culprit for this differential response is tobacco exposure.…”

Human Papilloma Virus Increases ΔNp63α Expression in Head and Neck Squamous Cell Carcinoma

“…HNC affect ∼600,000 patients per year worldwide and is the sixth leading cancer by incidence. Smoking is mainly implicated in the rise of HNC in developing countries, while the human papillomavirus (HPV) is an established important risk factor in the increase of oropharyngeal cancers in developed countries (Ang et al, 2010;Sabatini and Chiocca, 2019;Sandulache et al, 2019).…”

Incidence and survival for oropharynx and non‐oropharynx head and neck cancers among veterans living with HIV

“…Smoking is also a likely driver of poor outcomes, particularly in the Veteran population with high rates of tobacco use. Smoking worsens prognosis in HPV‐positive OPSCC, increasing the risk of death by 1% for every one pack‐year of smoking 30‐32 . However, to date, few studies have considered the interaction between HIV and HPV in OPSCC, and one previous study of OPSCC among PWLH found no difference in survival by HPV status, 33 This discordance justifies additional examination of the interaction between HPV and HIV in OPSCC specifically.…”