Al-Awadhi Rana, Alroomy Moody, Al-Waheeb Salah, Alwehaidah Materah Salem
Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Kuwait University, Jabriyah 90805, Kuwait.
Cytology Laboratory, Maternity Hospital and Mubarak Al-Kabeer Hospital, Ministry of Health, Kuwait University, Jabriyah 90805, Kuwait.
Exp Ther Med. 2023 Sep 21;26(5):521. doi: 10.3892/etm.2023.12220. eCollection 2023 Nov.
The majority of cervical cancer cases are due to human papillomavirus (HPV) infection. However, certain cases of cervical cancer are not caused by HPV. Recent studies have shown a link between altered mitochondrial DNA (mtDNA) copy number, an indicative measure of mitochondrial dysfunction, and cervical cancer in women who test positive for HPV. However, the role of the mtDNA copy number in HPV-negative cervical cancer has remained elusive. In the present study, the mtDNA copy number was determined using quantitative PCR as the ratio between mtDNA and nuclear DNA in 287 ThinPrep cervical samples, including 143 cases with cervical abnormalities and 144 control subjects with high-risk (hr)-HPV positive or HPV-negative status. In an overall analysis of cases categorized based on the cytology diagnosis into squamous cervical carcinoma/high-grade squamous intraepithelial lesions (SCC/HSIL), low-grade squamous intraepithelial lesions (LSIL) and normal controls, the mtDNA copy number was significantly higher in all cases compared to the controls and a higher mtDNA copy number was observed in SCC/HSIL compared to LSIL cases. In the stratification analyses based on hr-HPV positive and HPV-negative status, an increased mtDNA copy number was observed in the cases compared with the controls regardless of their HPV status (P<0.05). When cases with cervical abnormalities were categorized based on histological diagnosis into cervical intraepithelial neoplasia (CIN)2/CIN3 and CIN1, an overall analysis indicated an increased mtDNA copy number in CIN2/CIN3 compared to CIN1 (P=0.01). Stratification analyses of these cases based on HPV status revealed a higher mtDNA copy number in CIN2/CIN3 compared to CIN1 regardless of HPV infection (P<0.05). These results showed that an elevated mtDNA copy number in subjects with cervical abnormalities was not influenced by the HPV status and suggested the possibility of its role in the progression of cervical cancer. The increased mtDNA copy number may be an adaptive response mechanism to compensate for mtDNA oxidative stress and energy deficiency, possibly induced by HPV infection and other environmental exposures.
大多数宫颈癌病例是由人乳头瘤病毒（HPV）感染引起的。然而，某些宫颈癌病例并非由HPV引起。最近的研究表明，线粒体DNA（mtDNA）拷贝数改变（线粒体功能障碍的一项指示指标）与HPV检测呈阳性的女性宫颈癌之间存在联系。然而，mtDNA拷贝数在HPV阴性宫颈癌中的作用仍不清楚。在本研究中，使用定量PCR测定了287份ThinPrep宫颈样本中mtDNA与核DNA的比率，以此确定mtDNA拷贝数，这些样本包括143例宫颈异常病例和144例高危（hr）-HPV阳性或HPV阴性的对照受试者。在根据细胞学诊断分为宫颈鳞状细胞癌/高级别鳞状上皮内病变（SCC/HSIL）、低级别鳞状上皮内病变（LSIL）和正常对照的病例总体分析中，所有病例的mtDNA拷贝数均显著高于对照，且SCC/HSIL病例的mtDNA拷贝数高于LSIL病例。在基于hr-HPV阳性和HPV阴性状态的分层分析中，无论HPV状态如何，病例组的mtDNA拷贝数均高于对照组（P<0.05）。当根据组织学诊断将宫颈异常病例分为宫颈上皮内瘤变（CIN）2/CIN3和CIN1时，总体分析表明CIN2/CIN3的mtDNA拷贝数高于CIN1（P=0.01）。基于HPV状态对这些病例进行分层分析显示，无论HPV感染情况如何，CIN2/CIN3的mtDNA拷贝数均高于CIN1（P<0.05）。这些结果表明，宫颈异常受试者中mtDNA拷贝数升高不受HPV状态影响，并提示其在宫颈癌进展中发挥作用的可能性。mtDNA拷贝数增加可能是一种适应性反应机制，以补偿可能由HPV感染和其他环境暴露引起的mtDNA氧化应激和能量缺乏。
