Sadeghi Farzane, Mostaghimi Talieh, Taheri Mahdie, Yazdani Shahla, Javadian Maryam, Ranaee Mohammad, Ghorbani Hossein, Bouzari Zinatossadat, Sadeghi Farzin
Student Research Committee, Babol University of Medical Sciences, Babol, Iran.
Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
Front Oncol. 2024 Apr 24;14:1331862. doi: 10.3389/fonc.2024.1331862. eCollection 2024.
High-risk human papillomaviruses (HR-HPVs) are known to contribute to cervical cancer (CC), but the role of Epstein-Barr virus (EBV) in this process remains unclear, despite EBV's widespread detection in premalignant and malignant cervical tissues.
In this cross-sectional study of 258 cervical samples, including both formalin-fixed paraffin-embedded (FFPE) and fresh cervical tissues, the presence and viral load of HR-HPVs (HPV-16 and HPV-18) and EBV were evaluated in Iranian women with cervical intraepithelial neoplasia (CIN), squamous cell carcinoma (SCC), and a cervicitis control group using real-time PCR.
The study revealed a significant correlation between disease severity and both increased HPV-16 positivity and HPV-16 and HPV-18 co-infection (p<0.001). Interestingly, the control group had a higher frequency of EBV-positive cases than SCC/CIN groups (p<0.001). HPV-16 DNA load increased with disease severity (P<0.001), while HPV-18 showed no significant difference (P=0.058). The control group had a higher EBV DNA load compared to SCC/CIN groups (P=0.033). HPV-16 increased the risk of CIN II, CIN III, and SCC, while HPV-18 increased the risk of CIN II and CIN III. Notably, EBV was associated with a lower risk of CIN groups and SCC.
No significant difference in EBV co-infection with HPV-16/18 was found, failing to support the hypothesis that EBV is a cofactor in CC. However, high EBV viral load in the control group suggests a potential "hit and run hypothesis" role in CC progression. This hypothesis suggests that EBV may contribute briefly to the initiation of CC with an initial impact but then becomes less actively involved in its ongoing progression.
已知高危型人乳头瘤病毒（HR-HPVs）会引发宫颈癌（CC），但尽管在癌前和恶性宫颈组织中广泛检测到爱泼斯坦-巴尔病毒（EBV），其在这一过程中的作用仍不明确。
在这项对258份宫颈样本（包括福尔马林固定石蜡包埋（FFPE）样本和新鲜宫颈组织）的横断面研究中，采用实时聚合酶链反应评估伊朗患有宫颈上皮内瘤变（CIN）、鳞状细胞癌（SCC）的女性以及宫颈炎对照组中HR-HPVs（HPV-16和HPV-18）和EBV的存在情况及病毒载量。
研究显示疾病严重程度与HPV-16阳性率增加以及HPV-16和HPV-18合并感染之间存在显著相关性（p<0.001）。有趣的是，对照组中EBV阳性病例的频率高于SCC/CIN组（p<0.001）。HPV-16 DNA载量随疾病严重程度增加（P<0.001），而HPV-18无显著差异（P=0.058）。与SCC/CIN组相比，对照组的EBV DNA载量更高（P=0.033）。HPV-16增加了CIN II、CIN III和SCC的风险，而HPV-18增加了CIN II和CIN III的风险。值得注意的是，EBV与CIN组和SCC的较低风险相关。
未发现EBV与HPV-16/18合并感染存在显著差异，这无法支持EBV是宫颈癌辅助因子的假说。然而，对照组中高EBV病毒载量表明其在宫颈癌进展中可能具有潜在的“打了就跑假说”作用。该假说认为，EBV可能在宫颈癌起始阶段产生初步影响，但随后在其持续进展过程中参与度降低。
