Inukai Daisuke, Kan Taichi, Yamanaka Shunpei, Okamoto Hiroki, Fujimoto Yasushi, Ito Takanori, Taniguchi Natsuki, Yamamoto Yuuki, Tsuzuki Toyonori, Takami Akiyoshi, Ogawa Tetsuya
Department of Otolaryngology, Aichi Medical University, Nagakute, Aichi 480-1195, Japan.
Department of Surgical Pathology, Aichi Medical University Hospital, Nagakute, Aichi 480-1195, Japan.
Microorganisms. 2020 Sep 29;8(10):1497. doi: 10.3390/microorganisms8101497.
Human papillomavirus (HPV)-related, p16-positive oropharyngeal carcinoma is considered to be sensitive to anticancer drugs, and the standard treatment is therefore chemoradiotherapy, rather than surgery, especially for aggressive disease. However, with this higher sensitivity, chemotherapy alone may achieve a pathological complete response (CR), making radiation therapy unnecessary. A 46-year-old man with p16-positive squamous cell carcinoma (SCC) of the lateral oropharynx (palatine tonsil) underwent neoadjuvant chemotherapy. This achieved clinically significant tumor shrinkage and therefore surgery was performed for subsequent definitive treatment. Clinical and CT findings indicated a good effect of neoadjuvant chemotherapy on the tumor. A biopsy prior to chemotherapy revealed SCC, which demonstrated p16 immunoreactivity and positive signals for high-risk HPV by RNA in situ hybridization. The post-chemotherapy surgical specimen showed pathological CR and no p16 positive cells nor positive signals for high-risk HPV those were detected in the pre-chemotherapy specimen. There are some reports of chemotherapy alone achieving pathological CR in cases of p16-positive oropharyngeal carcinoma, but none have included high-risk HPV RNA findings. This is the first report of the disappearance of cancer cells as well as p16 staining and a positive signal for high-risk HPV. Achieving pathological CR confirmed by immunohistochemistry and high-risk HPV RNA in situ hybridization in a solid tumor with chemotherapy alone suggests that chemotherapy may have both an antitumor effect and an antiviral effect. Forgoing subsequent radiotherapy and undergoing surgery might be unnecessary and follow-up instead might be sufficient in such cases. Into the future, in an optimal tailored treatment approach, the option of neoadjuvant chemotherapy should be considered for management of p16-positive oropharyngeal carcinoma. Other options such as tumor immunotherapy are also expected to be effective.
人乳头瘤病毒（HPV）相关的、p16阳性的口咽癌被认为对抗癌药物敏感，因此标准治疗是放化疗，而非手术，尤其是对于侵袭性疾病。然而，鉴于这种较高的敏感性，单纯化疗可能实现病理完全缓解（CR），从而无需进行放射治疗。一名46岁的男性，患有侧口咽（腭扁桃体）p16阳性鳞状细胞癌（SCC），接受了新辅助化疗。这实现了临床上显著的肿瘤缩小，因此进行了手术以进行后续的确定性治疗。临床和CT检查结果表明新辅助化疗对肿瘤有良好效果。化疗前的活检显示为SCC，通过RNA原位杂交显示p16免疫反应性和高危HPV阳性信号。化疗后的手术标本显示病理CR，且未检测到化疗前标本中存在的p16阳性细胞或高危HPV阳性信号。有一些关于单纯化疗在p16阳性口咽癌病例中实现病理CR的报道，但均未包括高危HPV RNA检测结果。这是关于癌细胞以及p16染色和高危HPV阳性信号消失的首例报道。在实体瘤中单纯化疗通过免疫组化和高危HPV RNA原位杂交证实实现病理CR，提示化疗可能兼具抗肿瘤作用和抗病毒作用。在这类病例中，放弃后续放疗而进行手术可能不必要，随访或许就足够了。展望未来，在最佳的个体化治疗方案中，对于p16阳性口咽癌的管理应考虑新辅助化疗选项。其他选项如肿瘤免疫疗法也有望有效。
