Khanal Sujita, Shumway Brian S, Zahin Maryam, Redman Rebecca A, Strickley John D, Trainor Patrick J, Rai Shesh N, Ghim Shin-Je, Jenson Alfred Bennett, Joh Joongho
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Department of Surgical and Hospital Dentistry, University of Louisville School of Dentistry, Louisville, KY, USA.
Oncotarget. 2018 Jul 13;9(54):30419-30433. doi: 10.18632/oncotarget.25754.
This study evaluated the integration and methlyation of human papillomavirus type 16 (HPV16) in head and neck squamous cell carcinoma (HNSCC) and its oral precursor, high-grade oral epithelial dysplasia (hgOED). Archival samples of HPV16-positive hgOED ( = 19) and HNSCC ( = 15) were evaluated, along with three HNSCC (UMSCC-1, -47 and -104) and two cervical cancer (SiHa and CaSki) cell lines. HgOED cases were stratified into three groups with increasing degrees of cytologic changes (mitosis, karyorrhexis and apoptosis). The viral load was higher and the E2/E6 ratio lower (indicating a greater tendency toward viral integration) in group 3 than in groups 1 or 2 ( = 0.002, 0.03). Methylation was not observed in hgOED cases and occurred variably in only three HNSCC cases (26.67%, 60.0% and 93.3%). In HNSCC cell lines, lower E7 expression correlated with higher levels of methylation. HgOED with increased cytologic change, now termed HPV-associated oral epithelial dysplasia (HPV-OED), exhibited an increased viral load and a tendency toward DNA integration, suggesting a potentially increased risk for malignant transformation. More detailed characterization and clinical follow-up of HPV-OED patients is needed to determine whether HPV-OED is a true precursor to HPV-associated HNSCC and to clarify the involvement of HPV in HNSCC carcinogenesis.
本研究评估了16型人乳头瘤病毒（HPV16）在头颈部鳞状细胞癌（HNSCC）及其口腔前驱病变——高级别口腔上皮发育异常（hgOED）中的整合及甲基化情况。对HPV16阳性的hgOED（n = 19）和HNSCC（n = 15）的存档样本进行了评估，同时评估了3种HNSCC（UMSCC - 1、- 47和- 104）及2种宫颈癌（SiHa和CaSki）细胞系。将hgOED病例根据细胞学变化程度（有丝分裂、核固缩和凋亡）分为3组。第3组的病毒载量更高，E2/E6比值更低（表明病毒整合倾向更大），与第1组或第2组相比差异有统计学意义（P = 0.002，0.03）。在hgOED病例中未观察到甲基化，仅在3例HNSCC病例中出现不同程度的甲基化（26.67%、60.0%和93.3%）。在HNSCC细胞系中，E7表达降低与甲基化水平升高相关。细胞学变化增加的hgOED，现称为HPV相关口腔上皮发育异常（HPV - OED），其病毒载量增加且有DNA整合倾向，提示恶性转化风险可能增加。需要对HPV - OED患者进行更详细的特征分析和临床随访，以确定HPV - OED是否为HPV相关HNSCC的真正前驱病变，并阐明HPV在HNSCC致癌过程中的作用。
