早期识别人乳头瘤病毒相关口咽鳞状细胞癌(HPV(+)OPSCC)具有挑战性，需要新的生物标志物。我们假设在HPV(+)宫颈鳞状细胞癌(CSCC)中发现的甲基化DNA标记( MDMs)组合在HPV(+)OPSCC组织中具有类似的区分度。获取了经福尔马林固定、包埋的来自原发性HPV(+)OPSCC或HPV(+)CSCC患者的组织。对照组织包括正常咽喉腭扁桃体(NOP)和宫颈(NCS)。利用甲基化特异性聚合酶链反应，评估了组织提取的DNA上的21个之前经验证的宫颈MDMs。使用曲线下面积(AUC)评估了病例与对照组织之间的区分度，包括宫颈和咽喉组织。符合纳入标准的患者包括34例HPV(+)OPSCC，36例HPV(+)CSCC，26例NOP和24例NCS。在HPV(+)CSCC中，18/21 (86%)的MDMs实现了AUC≥0.9，所有MDMs相对于对照宫颈组织都表现出优于偶然的分类结果(all p < 0.001)。相比之下，在HPV(+)OPSCC中，只有5/21 (24%)的MDMs实现了AUC≥0.90，但有19/21 (90%)的MDMs相对于对照扁桃组织都表现出优于偶然的分类结果(all p < 0.001)。总体上，13/21个MDMs的AUC在咽喉组中与宫颈组相比具有统计学上显著较低的数值，只有1个MDM的AUC呈现统计学上显著增加。之前经验证的MDMs在独立HPV(+)CSCC患者中表现出稳健的性能。然而，大多数这些MDMs在HPV(+)OPSCC中的区分度较HPV(+)CSCC而言更高。这表明每种鳞状细胞癌亚型需要一套独特的MDMs以实现最佳区分度。未来的研究需要建立适用于HPV(+)OPSCC的MDM组合。版权所有 © 2023 Elsevier Ltd. 保留所有权利。

Early identification of human papillomavirus associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) is challenging and novel biomarkers are needed. We hypothesized that a panel of methylated DNA markers (MDMs) found in HPV(+) cervical squamous cell carcinoma (CSCC) will have similar discrimination in HPV(+)OPSCC tissues.Formalin-fixed, paraffin-embedded tissues were obtained from patients with primary HPV(+)OPSCC or HPV(+)CSCC; control tissues included normal oropharynx palatine tonsil (NOP) and cervix (NCS). Using a methylation-specific polymerase chain reaction, 21 previously validated cervical MDMs were evaluated on tissue-extracted DNA. Discrimination between case and control cervical and oropharynx tissue was assessed using area under the curve (AUC).34 HPV(+)OPSCC, 36 HPV(+)CSCC, 26 NOP, and 24 NCS patients met inclusion criteria. Within HPV(+)CSCC, 18/21 (86%) of MDMs achieved an AUC ≥ 0.9 and all MDMs exhibited better than chance classifications relative to control cervical tissue (all p < 0.001). In contrast, within HPV(+)OPSCC only 5/21 (24%) MDMs achieved an AUC ≥ 0.90 but 19/21 (90%) exhibited better than chance classifications relative to control tonsil tissue (all p < 0.001). Overall, 13/21 MDMs had statistically significant lower AUCs in the oropharyngeal cohort compared to the cervical cohort, and only 1 MDM exhibited a statistically significant increase in AUC.Previously validated MDMs exhibited robust performance in independent HPV(+)CSCC patients. However, most of these MDMs exhibited higher discrimination for HPV(+)CSCC than for HPV(+)OPSCC. This suggests that each SCC subtype requires a unique set of MDMs for optimal discrimination. Future studies are necessary to establish an MDM panel for HPV(+)OPSCC.Copyright © 2023 Elsevier Ltd. All rights reserved.