高危型HPV16/18感染联合肿瘤标志物CEA、CA199在宫颈癌诊断中的关联性分析

Association Analysis of High-Risk HPV16/18 Infection Combined with Tumor Markers CEA and CA199 in the Diagnosis of Cervical Cancer

摘要: 目的：探讨血清癌胚抗原(CEA)、糖类抗原199 (CA199)以及高危型人乳头瘤病毒16/18 (HR-HPV16/18)感染与宫颈病变之间的关系，评估上述标志物在宫颈癌早期筛查中的潜在应用价值。方法：选取2022年6月~2022年12月1于湘西土家族苗族自治州人民医院就诊并治疗的300例宫颈病变患者，根据宫颈病变程度分为宫颈癌(CC)组(132例)和宫颈上皮内瘤变(CIN)组(168例)。通过阴道镜宫颈活检、HR-HPV16/18检测及血清CEA、CA199水平测定等技术手段，比较两组患者在血清CEA、CA199水平及HR-HPV16/18阳性率差异，应用卡方检验和方差检验分析其关联性，并探讨HR-HPV16/18、血清肿瘤标志物在CIN进展为CC中的预测价值。结果：最终纳入CC组患者132例，均为鳞癌，平均年龄(52.5 ± 12.6)岁；CIN组患者168例，CIN II~III组122例，CIN I组46例，平均年龄(50.0±10.8)岁。CC组患者的血液CEA水平(7.295 ± 3.24 ng/ml VS 5.445 ± 2.69 ng/ml)、CA199水平(32.048 ± 15.75 mIU/ml VS 25.735 ± 15.78 mIU/ml)和HR-HPV16/18阳性率(77.3% VS 44.3%)均显著高于CIN II~III级患者，CIN II~III组患者的血液CEA水平(5.445 ± 2.69 ng/ml VS 3.989 ± 2.28 ng/ml)、CA199水平(25.735 ± 15.78 mIU/ml VS 17.733 ± 12.28 mIU/ml)和HR-HPV16/18阳性率(44.3% VS 30.4%)均显著高于CIN I级患者，差异具有统计学意义(P < 0.05)。表明CEA、CA199水平和HR-HPV16/18感染情况与宫颈病变的严重程度密切相关。HR-HPV16/18、CEA、CA199预测CIN进展为CC的曲线下面积(AUC)分别为0.684、0.702、0.610，三者联合预测的AUC最大，为0.723 (P < 0.05)。表明HR-HPV16/18、CEA、CA199联合预测CIN进展为CC方面拥有良好的临床效能。结论：与宫颈上皮内瘤变患者相比，宫颈癌患者的血清CEA、CA199和HR-HPV16/18阳性率均较高，这些标志物对宫颈癌的临床诊断具有重要意义。HR-HPV16/18、CEA和CA199联合检测可显著提高宫颈癌早期筛查的灵敏度和特异性，为宫颈癌的早期诊断提供新的思路和依据。

Abstract: Objective: To investigate the relationship between serum carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), high-risk human papillomavirus 16/18 (HR-HPV16/18) infection, and cervical lesions, and to evaluate the potential application value of these markers in early cervical cancer screening. Methods: A total of 300 patients with cervical lesions treated at Xiangxi Tujia and Miao Autonomous Prefecture People’s Hospital from June 2022 to December 2022 were selected. Based on the severity of cervical lesions, patients were divided into a cervical cancer (CC) group (132 cases) and a cervical intraepithelial neoplasia (CIN) group (168 cases). Techniques including cervical biopsy under colposcopy, HR-HPV16/18 testing, and serum CEA and CA199 level measurements were employed to compare differences in the serum levels of CEA, CA199, and HR-HPV16/18 positivity rates between the two groups. Chi-square test and analysis of variance (ANOVA) were used to analyze their associations, and the predictive value of high-risk human papillomavirus types 16/18 (HR-HPV16/18) and serum tumor markers in the progression from cervical intraepithelial neoplasia (CIN) to cervical cancer (CC) was explored. Results: The CC group included 132 patients (all with squamous cell carcinoma, mean age 52.5 ± 12.6 years), the CIN group included 168 patients (mean age 50.0 ± 10.8 years), the CIN II~III group included 122 patients and the CIN I group included 46 patients. Serum CEA levels (7.295 ± 3.24 ng/ml VS 5.445 ± 2.69 ng/ml), CA199 levels (32.048 ± 15.75 mIU/ml VS 25.735 ± 15.78 mIU/ml), and HR-HPV16/18 positivity rates (77.3% VS 44.3%) in the cervical cancer (CC) group were significantly higher than those in the CIN II~III group. Similarly, the CIN II~III group exhibited significantly elevated serum CEA levels (5.445 ± 2.69 ng/ml VS 3.989 ± 2.28 ng/ml), CA199 levels (25.735 ± 15.78 mIU/ml VS 17.733 ± 12.28 mIU/ml), and HR-HPV16/18 positivity rates (44.3% VS 30.4%) compared to the CIN I group, with all differences being statistically significant (P < 0.05). These findings indicate that CEA, CA199 levels, and HR-HPV16/18 infection status are closely associated with the severity of cervical lesions. The area under curve (AUC) values for predicting CIN progression to CC were 0.684 for HR-HPV16/18, 0.702 for CEA, and 0.610 for CA199. The combined prediction model demonstrated the highest AUC of 0.723 (P < 0.05), suggesting that the integration of HR-HPV16/18, CEA, and CA199 provides good clinical efficacy in predicting CIN progression to CC. Conclusion: Compared to patients with cervical intraepithelial neoplasia, cervical cancer patients exhibit higher positivity rates for serum CEA, CA199 and HR-HPV. These markers hold significant clinical diagnostic value for cervical cancer. Combined detection of HR-HPV16/18, CEA and CA199 can significantly improve the sensitivity and specificity of early cervical cancer screening, providing novel insights and evidence for early diagnosis.