Randomized Trial of Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Long-Term Results of the ORATOR Trial

PURPOSE The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has risen rapidly, because of an epidemic of human papillomavirus infection. The optimal management of early-stage OPSCC with surgery or radiation continues to be a clinical controversy. Long-term randomized data comparing these paradigms are lacking. METHODS We randomly assigned patients with T1-T2, N0-2 (≤ 4 cm) OPSCC to radiotherapy (RT) (with chemotherapy if N1-2) versus transoral robotic surgery plus neck dissection (TORS + ND) (with or without adjuvant therapy). The primary end point was swallowing quality of life (QOL) at 1-year using the MD Anderson Dysphagia Inventory. Secondary end points included adverse events, other QOL outcomes, overall survival, and progression-free survival. All analyses were intention-to-treat. Herein, we present long-term outcomes from the trial. RESULTS Sixty-eight patients were randomly assigned (n = 34 per arm) between August 10, 2012, and June 9, 2017. Median follow-up was 45 months. Longitudinal MD Anderson Dysphagia Inventory analyses demonstrated statistical superiority of RT arm over time ( P = .049), although the differences beyond 1 year were of smaller magnitude than at the 1-year timepoint (year 2: 86.0 ± 13.5 in the RT arm v 84.8 ± 12.5 in the TORS + ND arm, P = .74; year 3: 88.9 ± 11.3 v 83.3 ± 13.9, P = .12). These differences did not meet the threshold to qualify as a clinically meaningful change at any timepoint. Certain differences in QOL concerns including more pain and dental concerns in the TORS + ND arm seen at 1 year resolved at 2 and 3 years; however, TORS patients started to use more nutritional supplements at 3 years ( P = .015). Dry mouth scores were higher in RT patients over time ( P = .041). CONCLUSION On longitudinal analysis, the swallowing QOL difference between primary RT and TORS + ND approaches persists but decreases over time. Patients with OPSCC should be informed about the pros and cons of both treatment options (ClinicalTrials.gov identifier: NCT01590355 ).

P16 expression and clinicopathological features of oral and oropharyngeal squamous cell carcinoma

Background: There is an epidemiological shift in head and neck squamous cell carcinoma (HNSCC) attributable to HPV infection. HPV positive HNSCC has unique biology, risk factors, clinicopathological characteristics and outcome. There is a large variation in the published prevalence of HPV-related HNSCCs in India ranging from 7 to 78.7%. This study aims to find the P16 expression in the oral cavity and oropharyngeal SCC, thereby prevalence of HPV in our setting and to define the clinicopathological characteristics of HPV positive tumours in our setting.Methods: 210 specimens of primary Oral squamous cell carcinoma (OSCC) and Oropharyngeal Squamous cell carcinoma (OPSCC) were included. Immunohistochemistry was done using monoclonal mouse p16 antibody. Clinical details of each case were collected. Analysis was done using SPSS software and the association of P16 and clinicopathological variables were calculated using Fishers exact test.Results: P16 positive expression is observed only in 1/122 (0.82%) of OSCC and 8/88 (9%) of OPSCC. P16 positivity showed significant association with Grade of tumor (p= 0.008) and histological variant of SCC (p=0.00). 77.7% of P16 positive tumours are Grade 2 and 66.6% of Basaloid SCC was P16 positive. There is no significant association between p16 expression and other variables (subsite, age, gender, alcoholism, smoking, betel chewing and stage).Conclusions: P16 positivity was higher in oropharyngeal than in oral cancer. However, the HPV positivity rates are lower than other parts of India.

The Prevalence of Human Papillomavirus–Positive Oropharyngeal Squamous Cell Carcinoma at One of the Largest Tertiary Care Centers in Sub-Saharan Africa

Context.— Limited data exist on the prevalence of human papillomavirus (HPV)–positive oropharyngeal squamous cell carcinoma in sub-Saharan Africa. Objective.— To determine the prevalence of HPV-positive oropharyngeal squamous cell carcinoma at a large tertiary care center in South Africa. Design.— A total of 266 oropharyngeal squamous cell carcinomas diagnosed during an 11-year period (2007–2017) were selected for evaluation. Cases staining positive for p16 immunohistochemistry were evaluated for high-risk HPV using the BD Onclarity assay (BD Diagnostics, Sparks, Maryland). Results.— Of 266 oropharyngeal squamous cell carcinomas, 14% (n = 36) were positive for p16. Polymerase chain reaction for high-risk HPV performed on the p16-positive cases was negative in 23 cases and positive in 13 cases (13 of 266; 5%). p16 showed a positive predictive value of 36.1%. The HPV subtypes were HPV-16 (n = 10), HPV-18 (n = 1), HPV-52 (n = 1), and HPV-31 (n = 1). Human papillomavirus–positive cases occurred in 10 men and 3 women (mean age, 51 years) and arose from the tonsil (n = 10) or base of the tongue (n = 3). The HPV-positive cases were non-keratinizing (n = 10) or partially keratinizing (n = 1). Partially/nonkeratinizing cases revealed a modest improvement in p16 positive predictive value (11 of 21; 52.4%). Conclusions.— The presence of high-risk HPV in 5% of cases suggests that high-risk HPV is a minor etiologic agent in oropharyngeal squamous cell carcinoma in this region. Given its suboptimal positive predictive value, p16 is not a reliable marker for high-risk HPV infection in this region. When p16 is positive, HPV-specific testing is necessary. The identification of less common high-risk HPV types, HPV-52 and HPV-31, may influence current local vaccination strategies.