Human papillomavirus (HPV) negative oropharyngeal squamous cell carcinoma (OPSCC) is associated with worse survival when compared to HPV positive. Primary surgery is one option to intensify therapy in this high-risk group of patients. Unfortunately, the only randomized trial to explore this approach (RTOG 1221) failed to accrue and the role of primary surgery in the treatment of HPV-negative OPSCC remains unanswered.
Methods: A systematic review and meta-analysis were performed to examine the outcomes of surgery in the treatment of HPV-negative OPSCC. We used the PRISMA statement for reporting and queried Pubmed, Web of Science and the Cochrane databases for studies examining the use of primary surgery in the treatment of HPV-negative OPSCC. Excluded from analysis were reviews, commentaries, case series with fewer than 10 patients, and studies that included HPV-negative head and neck cancers of mixed sites. Our primary outcomes were 2-year and 5-year overall survival (OS) and disease-free survival (DFS). OS and DFS were pooled using meta-analysis of proportions.
Results: Twelve studies including a total of 1,447 patients were identified. Overall, 1,101 patients (76%) had small primary tumors (T1-T2) and 253 (24%) large primary tumors (T3-T4). Most patients included in the analysis 787 (54%) were treated with primary surgery: 576 transoral and 211 open. The average rate of positive margins was 16.45% (SD=14.72%). The average rate of patients who underwent risk stratified adjuvant therapy was 64.95%. The rate of patients who underwent adjuvant radiation therapy was 37.48% and adjuvant chemoradiation therapy was 27.47%. The average follow-up was 32.7 months (SD=12.47 months). Pooled two-year and five-year OS for patients undergoing any surgery was 88% (95% CI 81-94%, I2=65%; 6 studies) and 70% (95% CI 30-97%, I2=96%; 3 studies), respectively. Pooled two-year and five-year DFS for patients undergoing any surgery was 77% (95% CI 66-86%, I2=55%; 6 studies) and 59% (95% CI 50-69%, I2=0%; 3 studies), respectively. Pooled two-year and five-year OS for patients undergoing transoral surgery was 92% (95% CI 88-96%, I2=20%; 5 studies) and 87% (95% CI 79-94%, I2=undetermined; 2 studies), respectively. Pooled two-year and five-year DFS for patients undergoing transoral surgery was 78% (95% CI 63-90%, I2=56%; 4 studies) and 59% (95% CI 47-71%, I2=undetermined; 2 studies), respectively.
Conclusions: The two- and five-year OS for patients with HPV-negative OPSCC treated with any surgical approach and pathology-directed adjuvant therapy is 88% and 70%, respectively. The two-year and five-year OS for HPV-negative OPCSCC treated with trans oral surgery and pathology-directed adjuvant therapy is 92% and 87%, respectively.