McArdle Erica, Bulbul Mustafa, Collins Chantz, Duvvuri Umamaheswar, Gross Neil, Turner Meghan
Department of Otolaryngology-Head and Neck Surgery, West Virginia University, Morgantown, West Virginia, USA.
Department of Health Sciences, West Virginia University, Morgantown, West Virginia, USA.
Head Neck. 2025 Jun;47(6):1749-1757. doi: 10.1002/hed.28088. Epub 2025 Jan 27.
Human papillomavirus (HPV) negative oropharyngeal squamous cell carcinoma (OPSCC) is associated with worse survival when compared to HPV-positive OPSCC. 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.
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.
A total of 15 studies were included in qualitative synthesis and 11 were included in the meta-analysis. There were 923 patients total included. Eight studies including 483 patients reported staging of HPV negative disease, of which 81.6% had T1/T2 tumors and 41.4% had N0 nodal disease. The average rate of positive margins was 12.6%. The average rate of patients who underwent risk-stratified adjuvant RT was 30.7% and CRT was 29.5%. The average follow-up was 32.7 months (SD = 12.47 months). Only two studies reported survival outcomes for HPV-negative disease based on overall staging: 5-year OS was improved for stage III versus stage IV and early versus late stage disease. The pooled 2- and 5-year OS were 84% (95% CI 77%-91%, I = 52.4%; 5 studies) and 72% (95% CI 46%-92%, I = 95.5%; 4 studies), respectively. The pooled 2- and 5-year DFS for the entire population were 77% (95% CI 66%-86%, I = 55%; 6 studies) and 59% (95% CI 50%-69%, I = 0%; 3 studies). Of the subgroup undergoing TOS alone, the pooled 2- and 5-year OS were 87% (95% CI 79%-93%, I = 46.8%; 4 studies) and 82% (95% CI 69%-92%, I = 74.2%; 3 studies). The pooled 2- and 5-year DFS for the subgroup of patients undergoing TOS alone were 78% (95% CI 63%-90%, I = 56%; 4 studies) and 59% (95% CI 47%-71%, I = undetermined; 2 studies).
The two- and five-year OS for patients with HPV-negative OPSCC treated with any surgical approach and pathology-directed adjuvant therapy is 84% and 72%, respectively. The two- and five-year OS for HPV-negative OPCSCC treated with transoral surgery and pathology-directed adjuvant therapy is 87% and 82%, respectively.
与HPV阳性口咽鳞状细胞癌（OPSCC）相比，HPV阴性口咽鳞状细胞癌的生存率更低。对于这类高危患者群体，初次手术是强化治疗的一种选择。不幸的是，探索这种方法的唯一一项随机试验（RTOG 1221）未能招募到足够的患者，初次手术在HPV阴性OPSCC治疗中的作用仍未得到解答。
进行了一项系统评价和荟萃分析，以研究手术治疗HPV阴性OPSCC的疗效。我们使用PRISMA声明进行报告，并检索了PubMed、科学网和Cochrane数据库，以查找研究初次手术治疗HPV阴性OPSCC的研究。分析中排除了综述、评论、患者少于10例的病例系列，以及纳入混合部位HPV阴性头颈癌的研究。我们的主要结局是2年和5年总生存率（OS）和无病生存率（DFS）。OS和DFS采用比例荟萃分析进行汇总。
共有15项研究纳入定性综合分析，11项纳入荟萃分析。总共纳入923例患者。八项研究（共483例患者）报告了HPV阴性疾病的分期，其中81.6%为T1/T2肿瘤，41.4%为N0淋巴结疾病。切缘阳性的平均发生率为12.6%。接受风险分层辅助放疗的患者平均比例为30.7%，接受同步放化疗的患者平均比例为29.5%。平均随访时间为32.7个月（标准差=12.47个月）。只有两项研究根据总体分期报告了HPV阴性疾病的生存结局：III期与IV期以及早期与晚期疾病相比，5年OS有所改善。汇总的2年和5年OS分别为84%（95%CI 77%-91%，I²=52.4%；5项研究）和72%（95%CI 46%-92%，I²=95.5%；4项研究）。整个人群汇总的2年和5年DFS分别为77%（95%CI 66%-86%，I²=55%；6项研究）和59%（95%CI 50%-69%，I²=0%；3项研究）。在仅接受经口手术（TOS）的亚组中，汇总的2年和5年OS分别为87%（95%CI 79%-93%，I²=46.8%；4项研究）和82%（95%CI 69%-92%，I²=74.2%；3项研究）。仅接受TOS的患者亚组汇总的2年和5年DFS分别为78%（95%CI 63%-90%，I²=56%；4项研究）和59%（95%CI 47%-71%，I²=未确定；2项研究）。
采用任何手术方法和病理指导的辅助治疗的HPV阴性OPSCC患者的2年和5年OS分别为84%和72%。采用经口手术和病理指导的辅助治疗的HPV阴性OPCSCC患者的2年和5年OS分别为87%和82%。
