Vythilingam Divya I, Gautam Shweta Dutta, Santos Leonardo D, Xuan Wei, Rabiei Mohammad, Rajendra Shanmugarajah
Gastro-Intestinal Viral Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, Sydney, New South Wales, Australia.
St. Mary's Hospital, Isle of Wight, NHS England.
Clin Transl Gastroenterol. 2025 May 12;16(7):e00853. doi: 10.14309/ctg.0000000000000853. eCollection 2025 Jul 1.
Human papillomavirus (HPV) has been associated with a subset of Barrett dysplasia and esophageal adenocarcinoma (EAC). The HPV L1 capsid protein has been closely linked to disease regression and is a prognostic factor in HPV-driven cancers of the cervix and anus.
Thus, we investigated L1 protein expression in HPV-positive patients representing the esophageal squamous-Barrett metaplasia-dysplasia-adenocarcinoma sequence. L1 protein immunohistochemical staining was correlated with p16 overexpression and E6/E7 mRNA in situ hybridization.
Of 116 HPV DNA-positive patients ([age range: 19-90, mean [SD], 63.2 [13.5], 88 men and 28 women), 73 (62.9%) were genotype 16, 37 (31.9%) genotype 18, and 6 (5.2%) were genotype 6. L1 staining was identified in 64 individuals: 84.9% (28/33) controls, 94.1% (16/17) Barrett's esophagus, 50% (7/14) low-grade dysplasia, (8/21) 38.1% high-grade dysplasia, and 16.1% (5/31) EAC (adjusted P < 0.0001). Conversely, p16 was present in 9.1% (3/33) of controls, 17.7% (3/17) Barrett's esophagus, 57.1% (8/14) low-grade dysplasia, 61.9% (13/21) high-grade dysplasia, and 64.5% (20/31) of EAC patients ( P < 0.0001). Corresponding figures for E6/E7 mRNA positivity was 6.1% (2/33), 23.5% (4/17), 28.6% (4/14), 38.1% (8/21), and 45.2% (14/31), respectively ( P = 0.008). Expression of HPV-L1 and p16 or L1 and E6/E7 mRNA was largely mutually exclusive.
HPV L1 capsid expression is incrementally lost with increasing esophageal disease severity as in viral-driven anal and cervical lesions. Utility of L1 alone or in combination with p16 and or E6/E7 mRNA in stratifying HPV-positive patients for treatment should be explored in a prospective longitudinal investigation.
人乳头瘤病毒（HPV）与一部分巴雷特发育异常和食管腺癌（EAC）相关。HPV L1衣壳蛋白与疾病消退密切相关，并且是HPV驱动的宫颈癌和肛门癌的一个预后因素。
因此，我们研究了代表食管鳞状上皮-巴雷特化生-发育异常-腺癌序列的HPV阳性患者中L1蛋白的表达情况。L1蛋白免疫组化染色与p16过表达及E6/E7 mRNA原位杂交相关联。
在116例HPV DNA阳性患者中（年龄范围：19 - 90岁，平均[标准差]，63.2[13.5]，88例男性和28例女性），73例（62.9%）为16型，37例（31.9%）为18型，6例（5.2%）为6型。在64例个体中检测到L1染色：84.9%（28/33）为对照组，94.1%（16/17）为巴雷特食管，50%（7/14）为低级别发育异常，38.1%（8/21）为高级别发育异常，16.1%（5/31）为EAC（校正P<0.0001）。相反，p16在9.1%（3/33）的对照组、17.7%（3/17）的巴雷特食管、57.1%（8/14）的低级别发育异常、61.9%（13/21）的高级别发育异常以及64.5%（20/31）的EAC患者中存在（P<0.0001）。E6/E7 mRNA阳性的相应数据分别为6.1%（2/33）、23.5%（4/17）、28.6%（4/14）、38.1%（8/21）和45.2%（14/31）（P = 0.008）。HPV-L1与p16或L1与E6/E7 mRNA的表达在很大程度上相互排斥。
与病毒驱动的肛门和宫颈病变一样，随着食管疾病严重程度的增加，HPV L1衣壳表达逐渐丧失。应在前瞻性纵向研究中探索单独使用L1或联合p16和/或E6/E7 mRNA对HPV阳性患者进行分层治疗的效用。
