Performance of standardised colposcopy to detect cervical precancer and cancer for triage of women testing positive for human papillomavirus: results from the ESTAMPA multicentric screening study.
Performance of standardised colposcopy to detect cervical precancer and cancer for triage of women testing positive for human papillomavirus: results from the ESTAMPA multicentric screening study.
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DOI：
10.1016/s2214-109x(22)00545-9
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发表时间：
2023-03
影响因子：
34.3
通讯作者：
Almonte, Maribel
中科院分区：
文献类型：
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作者：
Valls, Joan;Baena, Armando;Venegas, Gino;Celis, Marcela;Gonzalez, Mauricio;Sosa, Carlos;Santin, Jorge Luis;Ortega, Marina;Soilan, Ana;Turcios, Elmer;Figueroa, Jacqueline;de la Pena, Margarita Rodriguez;Figueredo, Alicia;Beracochea, Andrea Veronica;Perez, Natalia;Martinez-Better, Josefina;Lora, Oscar;Jimenez, Julio Yamil;Gimenez, Diana;Fleider, Laura;Salgado, Yuly;Martinez, Sandra;Bellido-Fuentes, Yenny;Flores, Bettsy;Tatti, Silvio;Villagra, Veronica;Cruz-Valdez, Aurelio;Teran, Carolina;Sanchez, Gloria Ines;Rodriguez, Guillermo;Picconi, Maria Alejandra;Ferrera, Annabelle;Mendoza, Laura;Calderon, Alejandro;Murillo, Raul;Wiesner, Carolina;Broutet, Nathalie;Luciani, Silvana;Perez, Carlos;Darragh, Teresa M.;Jeronimo, Jose;Herrero, Rolando;Almonte, Maribel
阴道镜目前被纳入世卫组织的建议，作为对人类乳头瘤病毒(HPV)阳性妇女进行分类的一种选择，它仍然是指导活检以确认宫颈癌前病变和癌症以及治疗方法的参考标准。我们的目标是评估阴道镜检查在发现宫颈癌前病变和对HPV阳性妇女进行分类的癌症方面的性能。这项横断面多中心筛查研究在拉丁美洲(阿根廷、玻利维亚、哥伦比亚、哥斯达黎加、洪都拉斯、墨西哥、巴拉圭、秘鲁和乌拉圭)的12个中心(包括初级和二级保健中心、医院、实验室和大学)进行。符合条件的女性年龄在30-之间，性行为活跃，没有宫颈癌病史，也没有接受过宫颈癌前期治疗或子宫切除术，也没有计划搬出研究区域。对女性进行了HPV DNA检测和细胞学检查。HPV阳性妇女使用标准化方案进行阴道镜检查，包括对观察到的病变进行活检收集，对宫颈内标本进行3型变形区(TZ)采样，并根据需要进行治疗。18个月后，阴道镜检查正常或组织学无高度宫颈病变(低于宫颈上皮内瘤变(CIN)2级)的妇女被召回进行另一次HPV检测，以完成疾病确定；HPV阳性妇女被转介至第二次阴道镜检查，并根据需要进行活检和治疗。当阴道镜检查结果为阳性时，评估阴道镜诊断的准确性，当阴道镜检查结果为阳性时，阴道镜检查印迹为阳性、阳性、重大或疑似癌症，否则视为阴性。主要研究结果是在初次就诊或18个月就诊时检测到组织学证实的CIN3+(定义为3级或更差)。在2012年12月12日至2021年12月3日期间，共招募了42名 502女性，其中5985名(14.1%)检测为阳性。4499名疾病确诊和随访完全的参与者被纳入分析，他们的中位年龄为40·6岁(IQR 34·7-49·9)。在4499例初诊或18个月就诊的妇女中，有669例(14.9%)检测到CIN3+，其中3530例(78.5%)为阴性或CIN1,300例(6.7%)为CIN2,616例(13.7%)为CIN3，53例(1.2%)癌。CIN3+的敏感性为91·2%(95%CI 88·9~93·2)，特异性为50·1%(48·5~51·8)，低于CIN3的特异性为47·1%(45·5~48·7)。老年女性对CIN3+的敏感性显著降低(30~49岁组93.5%[95%CI 91·3~95·3]，50~65岁组77·6%[68·6~85·0]；P<；0·0001)，而CIN3+以下特异性显著升高(45·7%[43·8~47·6]vs 61·8%[58·7-·8]；P<；0·0001)。细胞学阴性的女性对CIN3+的敏感性也显著低于细胞学异常的女性(p<；0.0001)。阴道镜检查对HPV阳性女性的CIN3+检测是准确的。这些结果反映了Estanpa在一项为期18个月的后续战略中所做的努力，该战略通过国际验证的临床管理方案和包括质量改进实践在内的定期培训来最大限度地提高疾病检测能力。我们表明，阴道镜检查可以通过适当的标准化进行优化，用于HPV阳性女性的分诊。这些机构包括：世界卫生组织、泛美卫生组织、国际癌症控制联盟、国家癌症研究所、国家癌症研究所全球卫生中心、阿根廷和哥伦比亚国家研究、技术发展和创新促进机构、塞古罗社会党、巴拉圭国家科学和技术理事会、国际癌症研究机构以及所有当地合作机构。
Colposcopy, currently included in WHO recommendations as an option to triage human papillomavirus (HPV)-positive women, remains as the reference standard to guide both biopsy for confirmation of cervical precancer and cancer and treatment approaches. We aim to evaluate the performance of colposcopy to detect cervical precancer and cancer for triage in HPV-positive women. This cross-sectional, multicentric screening study was conducted at 12 centres (including primary and secondary care centres, hospitals, laboratories, and universities) in Latin America (Argentina, Bolivia, Colombia, Costa Rica, Honduras, Mexico, Paraguay, Peru, and Uruguay). Eligible women were aged 30–64 years, sexually active, did not have a history of cervical cancer or treatment for cervical precancer or a hysterectomy, and were not planning to move outside of the study area. Women were screened with HPV DNA testing and cytology. HPV-positive women were referred to colposcopy using a standardised protocol, including biopsy collection of observed lesions, endocervical sampling for transformation zone (TZ) type 3, and treatment as needed. Women with initial normal colposcopy or no high-grade cervical lesions on histology (less than cervical intraepithelial neoplasia [CIN] grade 2) were recalled after 18 months for another HPV test to complete disease ascertainment; HPV-positive women were referred for a second colposcopy with biopsy and treatment as needed. Diagnostic accuracy of colposcopy was assessed by considering a positive test result when the colposcopic impression at the initial colposcopy was positive minor, positive major, or suspected cancer, and was considered negative otherwise. The main study outcome was histologically confirmed CIN3+ (defined as grade 3 or worse) detected at the initial visit or 18-month visit. Between Dec 12, 2012, and Dec 3, 2021, 42 502 women were recruited, and 5985 (14·1%) tested positive for HPV. 4499 participants with complete disease ascertainment and follow-up were included in the analysis, with a median age of 40·6 years (IQR 34·7–49·9). CIN3+ was detected in 669 (14·9%) of 4499 women at the initial visit or 18-month visit (3530 [78·5%] negative or CIN1, 300 [6·7%] CIN2, 616 [13·7%] CIN3, and 53 [1·2%] cancers). Sensitivity was 91·2% (95% CI 88·9–93·2) for CIN3+, whereas specificity was 50·1% (48·5–51·8) for less than CIN2 and 47·1% (45·5–48·7) for less than CIN3. Sensitivity for CIN3+ significantly decreased in older women (93·5% [95% CI 91·3–95·3] in those aged 30–49 years vs 77·6% [68·6–85·0] in those aged 50–65 years; p<0·0001), whereas specificity for less than CIN2 significantly increased (45·7% [43·8–47·6] vs 61·8% [58·7–64·8]; p<0·0001). Sensitivity for CIN3+ was also significantly lower in women with negative cytology than in those with abnormal cytology (p<0·0001). Colposcopy is accurate for CIN3+ detection in HPV-positive women. These results reflect ESTAMPA efforts in an 18-month follow-up strategy to maximise disease detection with an internationally validated clinical management protocol and regular training, including quality improvement practices. We showed that colposcopy can be optimised with proper standardisation to be used as triage in HPV-positive women. WHO; Pan American Health Organization; Union for International Cancer Control; National Cancer Institute (NCI); NCI Center for Global Health; National Agency for the Promotion of Research, Technological Development, and Innovation; NCI of Argentina and Colombia; Caja Costarricense de Seguro Social; National Council for Science and Technology of Paraguay; International Agency for Research on Cancer; and all local collaborative institutions.