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Abstract：
Anal squamous cell carcinoma (SCC) treated with definitive radiotherapy (RT)/chemoradiotherapy (CRT) has shown high success rates, yet challenges such as treatment resistance and recurrence persist. The present study aimed to investigate the associations between immunohistochemical (IHC) evaluation, treatment response and prognosis in anal SCC. A retrospective cohort analysis included 42 patients with anal SCC treated at a single institution between 2006 and 2022. Human papillomavirus (HPV) status was determined, and the IHC analysis of p16, p53 and PD-L1 expression was conducted using formalin-fixed, paraffin-embedded biopsies. A complete response to RT/CRT was observed in 71.4% of patients. Recurrence occurred in 38.1% of cases, of which 7.1% had local-regional recurrence (LRR), 14.3% had distant recurrence (DR), and 16.7% had both LRR and DR. HPV positivity (71.4%) was significantly associated with p16 positivity. Lack of complete response was associated with HPV-negative status, p16-negative status, increased recurrence and DR. In addition, recurrence was significantly associated with p53-positive status, and p53 positivity was significantly associated with increased LRR. PD-L1 positivity, defined as a combined positive score (CPS) ≥1% was found in 73.8% of the patients, and exhibited significant associations with HPV positivity and p16 positivity. PD-L1 CPS ≥ 1% was also associated with an increased LRR. Univariate analysis revealed that age <65 years, a complete response and HPV positivity were associated with increased 5-year overall survival (OS), while a complete response, HPV positivity and p53-negative status were associated with increased 5-year disease-free survival (DFS). Multivariate analysis identified that age <65 years and HPV positivity are independent prognostic factors for 5-year OS, and a complete response and p53-negative status are independent prognostic factors for 5-year DFS. In conclusion, these findings suggust that the identification of HPV status and poor prognostic biomarkers at diagnosis may be used to guide personalized treatment strategies, with the combination of immunotherapy with standard CRT potentially providing improved outcomes.
摘要：
采用确定性放疗（RT）/放化疗（CRT）治疗的肛门鳞状细胞癌（SCC）已显示出很高的成功率，然而，治疗抵抗和复发等挑战仍然存在。本研究旨在探讨免疫组织化学（IHC）评估之间的关联，肛门SCC的治疗反应和预后。回顾性队列分析包括2006年至2022年间在单个机构接受治疗的42例肛门SCC患者。确定人乳头瘤病毒（HPV）状态，p16、p53和PD-L1表达的IHC分析使用福尔马林固定，石蜡包埋活检。在71.4%的患者中观察到对RT/CRT的完全反应。38.1%的病例复发,其中7.1%有局部区域复发(LRR)，14.3%有远处复发(DR),16.7%同时患有LRR和DR。HPV阳性（71.4%）与p16阳性显著相关。缺乏完全缓解与HPV阴性状态有关，p16-阴性状态，增加复发和DR.此外,复发与p53阳性状态显着相关，p53阳性与LRR升高显著相关。PD-L1阳性，定义为73.8%的患者发现合并阳性评分(CPS)≥1%，并与HPV阳性和p16阳性显着相关。PD-L1CPS≥1%也与LRR增加相关。单因素分析显示年龄<65岁,完全缓解和HPV阳性与5年总生存率（OS）增加有关，而一个完整的回应，HPV阳性和p53阴性状态与5年无病生存率（DFS）增加相关。多因素分析发现，年龄<65岁和HPV阳性是5年OS的独立预后因素。完全缓解和p53阴性状态是5年DFS的独立预后因素。总之,这些研究结果表明，在诊断时识别HPV状态和不良预后生物标志物可用于指导个性化治疗策略，免疫治疗与标准CRT的组合可能提供改善的结局。
