High-risk human papillomavirus (HPV) infection in conjunctival and lacrimal sac squamous cell carcinomas (SCCs) has been sporadically reported; however, its prevalence, clinicopathologic significance and surrogate markers have not been fully elucidated. Here, we attempted to clarify these questions in Japanese patients with conjunctiva and lacrimal sac SCCs. We retrospectively collected 51 conjunctival SCC and 7 lacrimal sac SCC samples and analyzed them for (1) transcriptionally active high-risk HPV infection using messenger RNA in situ hybridization and (2) protein expressions of p16 and Rb using immunohistochemistry (IHC). Among a total of 58 cases, 25 (43.1%) and 16 (27.6%) tumors were positive for p16-IHC and HPV in situ hybridization, respectively. Ten (19.6%) of the 51 conjunctival SCCs, especially in the palpebral conjunctiva, and 6 (85.7%) of the 7 lacrimal sac SCCs were positive for high-risk HPV. High-risk HPV infection was significantly associated with younger patients, nonkeratinizing SCC histology, p16-positivity and partial loss of Rb expression, but not with recurrence risk. Notably, p16-IHC was not a perfect surrogate marker for high-risk HPV infection; only 64% (16/25) of p16-positive tumors were positive for high-risk HPV. In contrast, the p16+/Rb partial loss pattern was exclusively correlated with high-risk HPV-positivity. The results suggest that the combination of p16 and Rb expression patterns by IHC could be a useful method to predict high-risk HPV infection in conjunctival and lacrimal sac SCCs. HPV infection may be of less prognostic value in this field of cancers.

结膜癌和泪囊鳞状细胞癌（SCC）中高危人乳头瘤病毒（HPV）感染已有零星报道；然而，其患病率、临床病理意义和替代标志物尚未完全阐明。在这里，我们试图在日本结膜和泪囊鳞状细胞癌患者中澄清这些问题。我们回顾性收集了 51 个结膜 SCC 和 7 个泪囊 SCC 样本，并使用信使 RNA 原位杂交分析了它们的 (1) 转录活性高危 HPV 感染，以及 (2) 使用免疫组织化学 (IHC) 分析了 p16 和 Rb 的蛋白表达。在总共 58 例病例中，p16-IHC 和 HPV 原位杂交分别有 25 例（43.1%）和 16 例（27.6%）肿瘤呈阳性。51 个结膜 SCC 中，有 10 个 (19.6%)，尤其是睑结膜，7 个泪囊 SCC 中有 6 个 (85.7%) 高危 HPV 阳性。高危 HPV 感染与年轻患者、非角化性 SCC 组织学、p16 阳性和 Rb 表达部分缺失显着相关，但与复发风险无关。值得注意的是，p16-IHC 并不是高危 HPV 感染的完美替代标志物；仅 64% (16/25) 的 p16 阳性肿瘤呈高危 HPV 阳性。相比之下，p16+/Rb 部分缺失模式与高危 HPV 阳性完全相关。结果表明，通过 IHC 结合 p16 和 Rb 表达模式可能是预测结膜和泪囊 SCC 中高危 HPV 感染的有用方法。HPV 感染在这一癌症领域的预后价值可能较低。