How Does Smoking Change the Clinicopathological Characteristics of Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma? One Medical Center Experience

Abstract

Introduction:Human papillomavirus (HPV)-positive and HPV-negative oropharyngeal squamous cell carcinomas (OPSCCs) are 2 distinct cancers, with HPV-positivity conferring a better prognosis. Smoking status is a complicating factor for both patient populations. There have been scattered literature that have reported on incomplete information regarding the profiles of their patient population. Details including age and sex distributions, TNM staging, histology grading, recurrence time and types, death rates, and the direct causes of deaths have been reported incompletely in the literature. Here, based on the experience at our university medical centers, we explored all the details of the important clinical profiles of HPV-negative OPSCC, HPV-positive OPSCC in smokers and nonsmokers.Objective:In this article, we compare detailed clinical profiles of HPV-negative OPSCC and HPV-positive OPSCC in both smokers and nonsmokers. The clinical profiles we elucidated here include patients’ age and sex distribution, general health conditions, histology grading, TNM staging, perineural invasion (PNI), and lymphovascular invasion (LVI), extracapsular extension (ECE), recurrence rate and types, death rate, and direct causes. Specifically, we divided HPV-positive OPSCC into smokers and nonsmokers and compared the different clinical profiles between these groups to give a better idea of the complicating role of smoking in the development of HPV-positive OPSCC.Method:All patients with OPSCC at a tertiary care publicly funded county hospital and a tertiary care university hospital from June 2009-July 2015 were retrospectively reviewed. The attending physicians were the same at both hospitals. The primary outcome measure was posttreatment 2-year follow-up status (locoregional recurrence, distant recurrence, death rate). Other measures included HPV status based on p16 staining, smoking history, age, sex, comorbidities, tumor size, nodal and distant metastasis information, LVI, PNI, ECE, and tumor histology grade.Results:A total of 202 patients with OPSCC were identified. They were categorized into 3 groups: HPV-negative OPSCC group (HPV−), HPV-positive smoker group (HPV+SMK+), and HPV-positive nonsmoker group (HPV+SMK−). Patients of HPV− group are older (61.1 ± 11.6 years) than the other groups on average. The HPV− group has the highest percentage of women (22.7%). The HPV− patients with OPSCC have more comorbidities than the HPV+SMK+ group and the HPV+SMK− group, although there is no statistical difference. Grade 2 tumor is the most common histology grade for HPV− patients with OPSCC, whereas grade 3 is the most common grade for HPV+SMK+ and HPV+SMK− groups. Both PNI and LVI are positive at around 40% for all groups without any significant difference, but ECE is very common for HPV− OPSCC, at 86.7%, which is significantly higher than that of the HPV+SMK+ and HPV+SMK− groups. There was no difference of bilateral neck metastases noticed among different groups. For T staging and N staging, although HPV+SMK− and HPV+SMK+ patients have relat...

Prognostic Significance of Smoking in Human Papillomavirus–Positive Oropharyngeal Cancer Under American Joint Committee on Cancer Eighth Edition Stage

“…Prior research has established that smoking negatively impacts prognosis in HPV‐positive OPSCC . However, there are few studies that examine smoking status in the context of AJCC‐8 staging guidelines.…”

“…Since the 1980s, HNC rates due to HPV have been rising, whereas the incidence of HNC associated with more traditional risk factors, such as tobacco, has decreased . The majority of HPV‐positive HNCs arise from the oropharynx, and these cancers are more common in younger patients and patients with a lower cumulative pack‐years or absent history of smoking . HPV‐positive oropharyngeal squamous cell carcinoma (OPSCC) has a better prognosis than its HPV‐negative counterpart .…”

“…Multiple studies have suggested that smoking negatively impacts outcomes in HPV‐positive cancers . One retrospective study found that smoking may have a greater impact on survival in low‐stage compared to high‐stage tumors when collectively examining all head and neck cancer sites .…”

Comparison of the Seventh and Eighth Edition of American Joint Committee on Cancer (AJCC) Staging for Selected and Nonselected Oropharyngeal Squamous Cell Carcinomas

“…Studies have shown that smoking is a negative prognostic factor in HPV-positive patients 20 and more specifically has been shown to increase death and recurrence rates of OPSCC in HPV-positive patients. 21 Ang et al detailed this relationship by purporting that tobacco use changes the biological behavior of HPV-positive OPSCC and can subsequently decrease responsiveness to the standard of care therapy. 22 …”

Impact of Smoking and Primary Tumor Subsite on Recurrence in HPV‐Associated Oropharyngeal Squamous Cell Carcinoma

“…Recent evidence also proposes that smoking may independently influence the histologic features and clinical behavior of HPV+ OPSCC, shifting it closer to characteristics of HPV– disease. 10 Thus, it is plausible that the interaction of HPV and smoking status produces OPSCC with distinct tumor behavior and treatment susceptibility. A better understanding of how smoking affects outcomes after OPSCC and whether this is affected by anatomic tumor site will help provide the most appropriate therapies given patients’ HPV status and smoking history.…”