摘要目的:探讨高危型人乳头状瘤病毒（HR-HPV）持续感染在年龄≤40岁的子宫颈上皮内瘤变Ⅱ（CINⅡ）患者期待治疗随访中的意义。方法:采用前瞻性队列研究，选择2019年1月至2020年12期就诊于南方医科大学深圳妇幼保健院门诊的年龄≤40岁、有生育需求、子宫颈转化区Ⅰ~Ⅱ型、阴道镜引导下点活检病理检查结果为CINⅡ的患者，采用HR-HPV分型检测、细胞学检查、阴道镜评估定期随访，拟随访2年。观察CINⅡ病变的自然转归，并分析HR-HPV持续感染在CINⅡ病变持续或进展中的预测价值。结果:共有135例CINⅡ患者纳入本研究，其随访时间为（26±11）个月；随访期间CINⅡ病变逆转率、病变持续率、病变进展率分别为65.2%（88/135）、20.0%（27/135）、14.8%（20/135），无一例患者进展至子宫颈癌。135例CINⅡ患者中，HR-HPV持续感染者68例（50.4%，68/135），HR-HPV非持续感染者为67例（49.6%，67/135）。HR-HPV持续感染患者的CINⅡ病变持续或进展率明显高于HR-HPV非持续感染者［分别为66.2%（45/68）、3.0%（2/67）； χ2=59.38， P<0.001］，HR-HPV持续感染为CINⅡ病变持续或进展的独立危险因素（ OR=30.93，95% CI为5.63~169.74， P<0.001）；HR-HPV持续感染预测CINⅡ病变持续或进展的敏感度、特异度分别为95.7%（45/47）、73.9%（65/88），预测CINⅡ病变进展的敏感度、特异度分别为100.0%（20/20）、58.3%（67/115）。86.4%（76/88）CINⅡ患者的病变逆转、83.6%（56/67）CINⅡ患者的HR-HPV转阴均出现在随访的第1年内。入组时42例HPV 16型和（或）18型（HPV 16/18型）感染患者的CINⅡ病变持续或进展率（47.6%，20/42）明显高于93例非HPV 16/18型感染者（29.0%，27/93； χ2=4.40， P=0.036）；HPV 16/18型持续感染患者的CINⅡ病变进展率（44.4%，12/27）明显高于非HPV 16/18型持续感染者（19.5%，8/41； χ2=4.87， P=0.027）。 结论:HR-HPV持续感染是预测年龄≤40岁CINⅡ患者病变持续或进展的敏感指标，可用作CINⅡ期待治疗的风险分层管理依据。CINⅡ病变逆转及HR-HPV转阴通常出现在期待治疗随访的第1年内，为降低病变进展风险，可将随访时间缩短至1年；对HR-HPV持续感染尤其是HPV 16/18型持续感染患者建议行手术治疗。

abstractsObjective:To analyze the value of high-risk human papillomavirus (HR-HPV) persistent infection in the follow-up of expectant treatment for cervical intraepithelial neoplasia (CIN) Ⅱ in patients aged ≤40 years.Methods:A prospective cohort study was conducted. Women aged ≤40 years with fertility needs, cervical transformation zone type Ⅰ-Ⅱ, and CIN Ⅱ pathology under colposcopy-guided biopsy were selected from the cervical outpatient clinic of Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University. HR-HPV genotyping test, cytological examination, and colposcopy evaluation were used for regular follow-up for 2 years. The natural outcomes of the lesions were obesrved, and the predictive value of HR-HPV persistent infection in the persistence or progression of CIN Ⅱ lesions was analyzed.Results:A total of 135 eligible patients were collected, and completed the follow-up for (26±11) months. Of them, 88 patients (65.2%, 88/135) showed regression, 27 (20.0%, 27/135) persistence to CIN Ⅱ, and 20 (14.8%, 20/135) progression to CIN Ⅲ (no one cervical cancer). Among 135 patients with CIN Ⅱ, there were 68 cases (50.4%, 68/135) of HR-HPV persistent infection and 67 cases (49.6%, 67/135) of HR-HPV non-persistent infection, respectively. The persistence or progression rate of CINⅡ lesions in patients with HR-HPV persistent infection was significantly higher than that in patients with HR-HPV non-persistent infection [66.2% (45/68) vs 3.0% (2/67); χ2=59.38, P<0.001]. HR-HPV persistent infection was an independent risk factor for persistence or progression of CIN Ⅱlesions ( OR=30.93, 95% CI: 5.63-169.74, P<0.001); with predictive sensitivity and specificity of 95.7% (45/47) and 73.9% (65/88), respectively, the sensitivity and specificity of predicting the progression of CIN Ⅱ lesions were 100.0% (20/20) and 58.3% (67/115), respectively. Within the first year of follow-up, 86.4% (76/88) of CIN Ⅱ patients showed lesion regression, and 83.6% (56/67) of CIN Ⅱ patients experienced HR-HPV conversion to negative. The persistence or progression rate of CIN Ⅱ lesions in 42 patients with HPV 16 and (or) 18 (HPV 16/18) infection (47.6%, 20/42) at the time of enrollment was significantly higher than that in 93 patients with other HR-HPV (not HPV 16/18) infection (29.0%, 27/93; χ2=4.40, P=0.036); the progression rate of CIN Ⅱ in patients with HPV 16/18 persistent infection (44.4%, 12/27) was significantly higher than that in patients with other HR-HPV (not HPV 16/18) persistent infection (19.5%, 8/41; χ2=4.87, P=0.027). Conclusions:HR-HPV persistent infection is a sensitive indicator to predict persistence or progression of CIN Ⅱ lesions in patients aged ≤40 years, which could be used as the basis for risk stratification management of expectant treatment of CIN Ⅱ. For CIN Ⅱ lesion regression and HR-HPV negative conversion usually occur within the first year, the follow-up time could be shortened to 1 year to reduce the risk of disease progression; surgical treatment is recommended for patients with HR-HPV persistent infection, especially HPV 16/18 infection.