Background: The incidence of human papilloma virus (HPV)-mediated head and neck (H/N) cancers has risen dramatically. While most HPV-associated H/N cancers are oropharyngeal squamous cell carcinoma (OPSCC), sinonasal squamous cell carcinoma (SNSCC) is the second most common. Recent studies highlight an increasing incidence of HPV-positive SNSCC. Circulating tumor HPV DNA (ctDNA) is a noninvasive tool that has become increasingly utilized to detect high-risk HPV genotypes in the setting of OPSCC, with recent studies reporting high sensitivity and specificity in both pretreatment detection and posttreatment surveillance in OPSCC. Only one study exists reporting its use for SNSCC and nasopharyngeal carcinoma, which was successful in pretreatment detection and identification of recurrence posttreatment.

Case reports: We report two cases demonstrating the utility of ctDNA in HPV-mediated sinonasal malignancies. Case 1: 60-year-old male who presented with a large nasal cavity cancer. Pretreatment ctDNA testing yielded a positive tumor tissue modified viral (TTMV)-HPV DNA Score of 67, reflective of the normalized tumor tissue modified viral-HPV DNA fragments/mL of plasma, and pathology confirmed HPV+ SNSCC. Posttreatment surveillance with HPV ctDNA and endoscopy has shown no evidence of disease. Case 2 involves a 64-year-old male with HPV+ neuroendocrine carcinoma who developed recurrence. ctDNA testing, previously negative following initial treatment, scored 35 at recurrence, prompting salvage surgery and adjuvant chemoradiation.

Conclusion: These cases, along with prior studies, underscore the potential of ctDNA as a diagnostic and surveillance tool for sinonasal malignancies. Further multi-institutional prospective trials with larger cohorts are needed to validate its role in detection and surveillance.

Keywords: HPV; circulating tumor DNA; liquid biopsy; sinonasal carcinoma; sinonasal squamous cell carcinoma.

The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).

背景：人乳头瘤病毒（HPV）介导的头部和颈部（H/N）癌症发病率急剧上升。虽然大多数与HPV相关的H/N癌症是口咽鳞状细胞癌（OPSCC），但鼻窦鳞状细胞癌（SNSCC）是第二大常见的类型。最近的研究强调了HPV阳性SNSCC发病率的增长。循环肿瘤HPV DNA (ctDNA) 是一种非侵入性工具，越来越常被用于检测OPSCC中的高风险HPV基因型，近期研究报道其在术前检测和术后监测中具有较高的灵敏度和特异性。仅有一项研究报告了它在SNSCC和鼻咽癌中的应用，在术前检测和术后复发识别方面均取得了成功。

病例报告：我们报告了两例展示ctDNA在HPV介导的鼻窦恶性肿瘤中实用性的案例。案例1：一名60岁男性因鼻腔大肿块就诊。术前ctDNA检测结果显示，经过修改后的病毒-HPV DNA分数为67分（代表标准化后的肿瘤组织修改病毒-HPV DNA片段每毫升血浆中的浓度），病理检查确认该病例为HPV阳性SNSCC。术后监测中使用了HPV ctDNA和内窥镜检查，并未发现任何疾病证据。案例2涉及一名64岁男性，其患有HPV阳性的神经内分泌癌并出现复发。ctDNA检测在初次治疗后结果曾呈阴性，在复发时分数为35分，这促使进行了挽救手术和辅助放化疗。

结论：这些案例以及之前的研究强调了ctDNA作为鼻窦恶性肿瘤诊断和监测工具的潜力。需要进一步多机构的前瞻性试验并采用更大的样本量来验证其在检测和监测中的作用。

关键词：HPV；循环肿瘤DNA；液态活检；鼻窦癌；鼻窦鳞状细胞癌。