Initial Symptoms in Patients With HPV-Positive and HPV-Negative Oropharyngeal Cancer

Abstract

IMPORTANCE This study addresses the most common initial symptoms of oropharyngeal squamous cell carcinoma (OPSCC) and investigates differences between human papillomavirus (HPV)–positive vs HPV-negative tumors. OBJECTIVES To analyze the most common initial symptoms in patients with OPSCC and to determine if any differences in initial symptoms occur between HPV-positive and HPV-negative tumors. DESIGN, SETTING, AND PATIENTS Retrospective single-institution review of medical records of previously untreated patients with OPSCC diagnosed from January 1, 2008, toMay 20, 2013, who were evaluated by 1 physician (the senior author, T.A.D.) at the Medical University of South Carolina. MAIN OUTCOMES AND MEASURES We determined the most common initial symptoms of OPSCC and analyzed differences between HPV-positive and HPV-negative tumors. RESULTS Neck mass (in 39 patients [44%]) and sore throat (in 29 patients [33%]) comprised the most common initial symptoms in OPSCC. Patients who were HPV-positive were more likely to initially notice a neck mass than HPV-negative patients (51% vs 18%; P = .02), whereas HPV-negative patients were more likely to notice sore throat (53%vs 28%; P = .09), dysphagia (41% vs 10%; P = .05), or odynophagia (24%vs 6%; P = .04). CONCLUSIONS AND RELEVANCE This study provides preliminary evidence supporting neck mass and sore throat as the initial symptoms of patients with OPSCC. Patients who were HPV-positive more commonly complained of a neck mass as the initial symptom, whereas HPV-negative patients more commonly had symptoms related to the primary tumor site, including sore throat, dysphagia, and/or odynophagia.

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What Is New in the 2017 WHO Blue Book for Tumors and Tumor-Like Lesions of the Neck and Lymph Nodes

“…As many as 90% of patients with HPV-positive OPSCC have neck lymph node metastases at presentation [7,8] and approximately 50% will present with neck, rather than primary tumor, symptoms [9]. Since the primary tumors are often small, arise in the reticulated tonsillar crypt epithelium deep to the surface, and engender little stromal reaction, they frequently present as neck nodal metastases without a clinically obvious primary lesion [9].…”

“…Since the primary tumors are often small, arise in the reticulated tonsillar crypt epithelium deep to the surface, and engender little stromal reaction, they frequently present as neck nodal metastases without a clinically obvious primary lesion [9]. Approximately 80% of patients presenting with metastatic SCC of unknown primary in the neck are related to transcriptionally-active high risk HPV.…”

The Growing Epidemic of HPV-Positive Oropharyngeal Carcinoma: A Clinical Review for Primary Care Providers

“…These differences in behavior affect every aspect of the disease, from initial symptoms noticed by the patient, to tumor location, size, likelihood and timing of lymph node spread, to response to therapy and quality of life after treatment. 4 HPVϩ oropharyngeal cancer is associated with younger age at diagnosis, oral sexual behavior as a primary risk factor, nonspecific presentation, and improved treatment response compared with HPVϪ disease. According to a meta-analysis by O'Rorke et al, 5 patients with HPVϩ OPSCC have more favorable overall survival (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.35-0.62); disease-specific survival (HR, 0.26; 95% CI, 0.17-0.39); and disease-free survival (HR, 0.37; 95% CI, 0.22-0.63).…”

“…It has been postulated that this histology contributes to the propensity of these tumors to metastasize earlier, whereas primary tumors are smaller and even occasionally present as cervical metastases with unknown primaries. 12 McIlwain et al 4 demonstrated that the most common initial symptom of HPVϩ OPSCC is a neck mass (51% of patients), whereas only 18% of patients with HPVϪ OPSCC presented with this symptom. Although HPVϩ OPSCC has a high rate of cervical metastases, even when the primary tumor is small and asymptomatic, it does not usually present with distant metastasis.…”

“…Because currently there are no standard tests to evaluate for precancerous OPSCC lesions (such as the Papanicolaou test and HPV DNA testing for cervical cancer), a detailed review of systems and physical examination remain the most important method for early detection. 4 Presenting Symptoms Prevalence (%)…”