Objective: To investigate the correlation of combined detection of p16 and Rb with high-risk human papilloma virus (HR-HPV) infection in non-oropharyngeal squamous cell carcinoma (NOPSCC) of the head and neck. Methods: A total of 68 NOPSCC cases of the head and neck (23 cases of the nasal cavity and paranasal sinuses and 45 cases of larynx) with complete clinical and pathological data, diagnosed at the Beijing Tongren Hospital, Capital Medical University, Beijing, China from November 2013 to December 2023, were collected. The expression of p16 and Rb was detected using immunohistochemistry of the EnVision two-step method, while the HR-HPV mRNA expression was detected using in situ hybridization. The concordance, sensitivity, and specificity of p16 alone and the combined detection of p16 and Rb for detecting HR-HPV infection were analyzed. Results: Among the 68 patients with NOPSCC, 53 were male and 15 were female, with a median age of 63.5 (range, 57.3 to 66.8) years. 41 patients had a smoking history and 27 did not. 33 patients had an early T stage (T1/T2) and 35 had advanced T stage (T3/T4). 14 patients had lymph node metastasis and 2 had distant metastasis. Histological types included 62 cases of keratinized squamous cell carcinoma, 5 cases of non-keratinized squamous cell carcinoma, and 1 case of basal-like squamous cell carcinoma. 25 cases were positive for p16. Among the 25 cases, 16 cases were positive for Rb, and 6 cases were positive for HR-HPV mRNA. 43 cases were negative for p16, including 38 cases positive for Rb and no cases positive for HR-HPV mRNA. The concordance between p16 and HR-HPV mRNA expression was poor (Kappa=0.285, P=0.001), with a sensitivity of 100.0% and specificity of 69.4%. In contrast, the combined detection of p16+/Rb- showed high concordance with HR-HPV mRNA expression (Kappa=0.719, P<0.001), with a sensitivity of 100.0% and specificity of 95.2%. Conclusions: In NOPSCC of the head and neck, the combined detection of p16 and Rb may be used as a marker for assessing HR-HPV infection. Recognizing the p16+/Rb- expression pattern in NOPSCC can improve the specificity of HR-HPV detection.
目的： 探讨p16、Rb联合检测在头颈部非口咽部鳞状细胞癌（non-oropharyngeal squamous cell carcinoma，NOPSCC）中与高危型人乳头状瘤病毒（high-risk human papilloma virus，HR-HPV）感染的相关性。 方法： 收集2013年11月至2023年12月首都医科大学附属北京同仁医院存档的有完整临床病理资料的68例头颈部NOPSCC标本蜡块（23例位于鼻腔鼻窦，45例位于喉），采用免疫组织化学EnVision两步法检测p16及Rb的表达，同时采用原位杂交法（in situ hybridization，ISH）检测HR-HPV mRNA的表达，分析p16单独检测及p16、Rb联合检测与HR-HPV mRNA表达的一致性、灵敏度及特异度。 结果： 68例NOPSCC患者，男性53例，女性15例，中位年龄63.5（57.3，66.8）岁，有吸烟史41例，无吸烟史27例；低T分期（T1/T2）33例，高T分期（T3/T4）35例；有淋巴结转移14例，无淋巴结转移54例；有远处转移2例，无远处转移66例。组织学类型：角化性鳞状细胞癌62例，非角化性鳞状细胞癌5例，基底样鳞状细胞癌1例。p16阳性25例（其中Rb阳性16例，阴性9例；HR-HPV mRNA阳性6例，阴性19例），p16阴性43例（其中Rb阳性38例，阴性5例；HR-HPV mRNA均阴性）。p16与HR-HPV mRNA表达一致性较差（Kappa值=0.285，P=0.001），灵敏度为100.0%，特异度为69.4%；p16+/Rb-联合检测与HR-HPV mRNA表达一致性较好（Kappa值=0.719，P<0.001），灵敏度为100.0%，特异度为95.2%。 结论： 在头颈部NOPSCC中，推荐p16和Rb免疫组织化学联合检测作为评估HR-HPV感染的指标，p16+/Rb-可提高检测的特异度。.