The role of Human papillomavirus (HPV) infection in esophageal squamous cell carcinoma (ESCC) is a topic of ongoing debate. This study used two screening approaches to look for evidence of HPV infection in esophageal squamous cell carcinoma. We initially checked for HPV infection in a randomly selected group of 53 ESCC cases. We did not detect any tumors positive for high-risk HPV. However, during clinical practice, we identified an HPV-positive ESCC in the distal esophagus, which tested positive for HPV16. This index case was TP53 wild-type, as determined by next-generation DNA sequencing (NGS). Since TP53 mutations are rare in other HPV-driven cancers, we improved our screening method by limiting our screen to a subset of ESCC cases without TP53 mutations. A second screen of 95 ESCCs (from 93 patients) sequenced by NGS revealed an additional 7 ESCCs with TP53 wild-type status (7.3% of the total). Of the 7 cases, 2 cases were found to be high-risk HPV positive. Both patients also tested positive for circulating cell-free HPV DNA and had a complete response to neoadjuvant chemoradiation. The index patient had microscopic residual tumor following neoadjuvant therapy. The patient underwent adjuvant immunotherapy and remained disease free after 22 months of surveillance. This study affirms the transcriptionally active status of high-risk HPV in a minority of ESCC patients in North America.

中文翻译：

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北美少数食管鳞状细胞癌中转录活跃的人乳头瘤病毒感染。


人乳头瘤病毒（HPV）感染在食管鳞状细胞癌（ESCC）中的作用是一个持续争论的话题。本研究使用两种筛查方法来寻找食管鳞状细胞癌中 HPV 感染的证据。我们最初在随机选择的 53 例 ESCC 病例中检查了 HPV 感染情况。我们没有检测到任何高危 HPV 阳性的肿瘤。然而，在临床实践中，我们在远端食管中发现了 HPV 阳性 ESCC，其 HPV16 检测呈阳性。根据下一代 DNA 测序 (NGS) 确定，该指示病例为 TP53 野生型。由于 TP53 突变在其他 HPV 驱动的癌症中很少见，因此我们通过将筛查限制在没有 TP53 突变的 ESCC 病例子集来改进我们的筛查方法。通过 NGS 测序对 95 个 ESCC（来自 93 名患者）进行的第二次筛查显示，另外 7 个 ESCC 具有 TP53 野生型状态（占总数的 7.3%）。 7例中，2例高危型HPV阳性。两名患者的循环游离 HPV DNA 检测也呈阳性，并对新辅助放化疗产生完全缓解。指示患者在新辅助治疗后有微小残留肿瘤。该患者接受了辅助免疫治疗，并在 22 个月的监测后保持无病状态。这项研究证实了北美少数 ESCC 患者中高危 HPV 的转录活跃状态。