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.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: 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.

[Tamoxifen and endometrial disease in patients with breast cancer]. / Tamoxifeno y afecciones endometriales en pacientes con cáncer de mama.

The objectives were to evaluate prevalence of endometrial disease in patients treated with tamoxifen (TAM) and analyze the epidemiological, sonographic, hysteroscopic and histopathological findings. From January 1999 to December 2008, 152 breast cancer patients treated with TAM (20 mg/day), symptomatic (with bleeding) or asymptomatic, pre-and postmenopausal, were included consecutively in a prospective and observational follow-up study. Diagnostic methods were (TV) transvaginal ultrasound, hysteroscopy and curettage biopsy. TV ultrasound was performed every 12 months for 12 to 60 months. The patients' age were 62.76 years ± 10.24 the TAM-time: 36.24 ± 19. Adenocarcinoma was observed in 3/87 patients (3.45%) with risk factors and in 1/65 (1.54%) without them (RA 1.91, IC 95% 1.88-1.94). We found benign disease in 148 patients (97.37%) and adenocarcinomas in 4 (2.63%), one within a polyp. The 4 adenocarcinomas were detected in postmenopausal women (2 asymptomatic) with endometrial thicknesses equal or greater than 16 mm. The cancer risk was significantly increased in symptomatic (2.36 versus 0.42 in asymptomatic). Three adenocarcinomas were observed between 24 and 48 months of treatment. In conclusion, we suggest an adequate transvaginal ultrasound monitoring of asymptomatic patients treated with TAM, with removal of polyps, because atypia can be present hidden within, considering risk factors and exposure time. We suggest as an acceptable cut-off = 10 mm in asymptomatic postmenopausal patients.

Tamoxifeno y afecciones endometriales en pacientes con cáncer de mama / Tamoxifen and endometrial disease in patients with breast cancer

Los objetivos fueron evaluar la prevalencia de afecciones endometriales en pacientes tratadas con tamoxifeno (TAM) y analizar los aspectos epidemiológicos, ecográficos, histeroscópicos e histopatológicos. Desde enero de 1999 a diciembre 2008 se estudiaron 152 pacientes con cáncer de mama tratadas con TAM (20 mg/día), sintomáticas (con sangrado) o asintomáticas, pre y postmenopáusicas, incluidas en forma consecutiva. El diseño fue prospectivo y observacional. Los métodos diagnósticos usados fueron ecografía transvaginal, histeroscopía y biopsia. Las pacientes fueron seguidas durante 5 años con ecografía cada 12 meses e histeroscopia con biopsia en casos que lo justificaran. Edad: 62.76 ± 10.24 años y tiempo de tratamiento: 36.2 ± 19.9 meses. El adenocarcinoma se observó en 3/87 (3.45%) pacientes con factores de riesgo y en 1/65 (1.54%) sin ellos (RA: 1.91, IC 95% 1.88 a 1.94). Las afecciones benignas se hallaron en 148 pacientes (97.37% y los adenocarcinomas en 4 (2.63%),1 en un pólipo de aspecto benigno. Los 4 se observaron en mujeres postmenopáusicas (2 asintomáticas) con grosor endometrial igual o mayor a 16 mm. El riesgo de cáncer fue significativamente mayor en sintomáticas (2.36 versus 0.42 en asintomáticas). Tres adenocarcinomas se detectaron entre 24 y 48 meses del tratamiento. Recomendamos un seguimiento con ecografía transvaginal de las pacientes asintomáticas, resección de los pólipos evaluando factores de riesgo y tiempo de exposición, en especial luego de los 24 meses. Consideramos aceptable un cut-off = 10 mm en el grosor del endometrio en postmenopáusicas asintomáticas para realizar histeroscopía y biopsia.

The objectives were to evaluate prevalence of endometrial disease in patients treated with tamoxifen (TAM) and analyze the epidemiological, sonographic, hysteroscopic and histopathological findings. From January 1999 to December 2008, 152 breast cancer patients treated with TAM (20 mg/day), symptomatic (with bleeding) or asymptomatic, pre- and postmenopausal, were included consecutively in a prospective and observational follow-up study Diagnostic methods were (TV) transvaginal ultrasound, hysteroscopy and curettage biopsy. TV ultrasound was performed every 12 months for 12 to 60 months. The patients´ age were 62.76 years ± 10.24 the TAM-time: 36.24 ± 19. Adenocarcinoma was observed in 3/87 patients (3.45%) with risk factors and in 1/65 (1.54%) without them (RA 1.91, IC 95% 1.88-1.94). We found benign disease in 148 patients (97.37%) and adenocarcinomas in 4 (2.63%), one within a polyp. The 4 adenocarcinomas were detected in postmenopausal women (2 asymptomatic) with endometrial thicknesses equal or greater than 16 mm. The cancer risk was significantly increased in symptomatic (2.36 versus 0.42 in asymptomatic). Three adenocarcinomas were observed between 24 and 48 months of treatment. In conclusion, we suggest an adequate transvaginal ultrasound monitoring of asymptomatic patients treated with TAM, with removal of polyps, because atypia can be present hidden within, considerin risk factors and exposure time. We suggest as an acceptable cut-off = 10 mm in asymptomatic postmenopausal patients.

Tamoxifeno y afecciones endometriales en pacientes con cáncer de mama / Tamoxifen and endometrial disease in patients with breast cancer

Los objetivos fueron evaluar la prevalencia de afecciones endometriales en pacientes tratadas con tamoxifeno (TAM) y analizar los aspectos epidemiológicos, ecográficos, histeroscópicos e histopatológicos. Desde enero de 1999 a diciembre 2008 se estudiaron 152 pacientes con cáncer de mama tratadas con TAM (20 mg/día), sintomáticas (con sangrado) o asintomáticas, pre y postmenopáusicas, incluidas en forma consecutiva. El diseño fue prospectivo y observacional. Los métodos diagnósticos usados fueron ecografía transvaginal, histeroscopía y biopsia. Las pacientes fueron seguidas durante 5 años con ecografía cada 12 meses e histeroscopia con biopsia en casos que lo justificaran. Edad: 62.76 ± 10.24 años y tiempo de tratamiento: 36.2 ± 19.9 meses. El adenocarcinoma se observó en 3/87 (3.45%) pacientes con factores de riesgo y en 1/65 (1.54%) sin ellos (RA: 1.91, IC 95% 1.88 a 1.94). Las afecciones benignas se hallaron en 148 pacientes (97.37% y los adenocarcinomas en 4 (2.63%),1 en un pólipo de aspecto benigno. Los 4 se observaron en mujeres postmenopáusicas (2 asintomáticas) con grosor endometrial igual o mayor a 16 mm. El riesgo de cáncer fue significativamente mayor en sintomáticas (2.36 versus 0.42 en asintomáticas). Tres adenocarcinomas se detectaron entre 24 y 48 meses del tratamiento. Recomendamos un seguimiento con ecografía transvaginal de las pacientes asintomáticas, resección de los pólipos evaluando factores de riesgo y tiempo de exposición, en especial luego de los 24 meses. Consideramos aceptable un cut-off = 10 mm en el grosor del endometrio en postmenopáusicas asintomáticas para realizar histeroscopía y biopsia.(AU)

The objectives were to evaluate prevalence of endometrial disease in patients treated with tamoxifen (TAM) and analyze the epidemiological, sonographic, hysteroscopic and histopathological findings. From January 1999 to December 2008, 152 breast cancer patients treated with TAM (20 mg/day), symptomatic (with bleeding) or asymptomatic, pre- and postmenopausal, were included consecutively in a prospective and observational follow-up study Diagnostic methods were (TV) transvaginal ultrasound, hysteroscopy and curettage biopsy. TV ultrasound was performed every 12 months for 12 to 60 months. The patients´ age were 62.76 years ± 10.24 the TAM-time: 36.24 ± 19. Adenocarcinoma was observed in 3/87 patients (3.45%) with risk factors and in 1/65 (1.54%) without them (RA 1.91, IC 95% 1.88-1.94). We found benign disease in 148 patients (97.37%) and adenocarcinomas in 4 (2.63%), one within a polyp. The 4 adenocarcinomas were detected in postmenopausal women (2 asymptomatic) with endometrial thicknesses equal or greater than 16 mm. The cancer risk was significantly increased in symptomatic (2.36 versus 0.42 in asymptomatic). Three adenocarcinomas were observed between 24 and 48 months of treatment. In conclusion, we suggest an adequate transvaginal ultrasound monitoring of asymptomatic patients treated with TAM, with removal of polyps, because atypia can be present hidden within, considerin risk factors and exposure time. We suggest as an acceptable cut-off = 10 mm in asymptomatic postmenopausal patients.(AU)

Tamoxifeno y afecciones endometriales en pacientes con cáncer de mama. / [Tamoxifen and endometrial disease in patients with breast cancer].

The objectives were to evaluate prevalence of endometrial disease in patients treated with tamoxifen (TAM) and analyze the epidemiological, sonographic, hysteroscopic and histopathological findings. From January 1999 to December 2008, 152 breast cancer patients treated with TAM (20 mg/day), symptomatic (with bleeding) or asymptomatic, pre-and postmenopausal, were included consecutively in a prospective and observational follow-up study. Diagnostic methods were (TV) transvaginal ultrasound, hysteroscopy and curettage biopsy. TV ultrasound was performed every 12 months for 12 to 60 months. The patients age were 62.76 years ± 10.24 the TAM-time: 36.24 ± 19. Adenocarcinoma was observed in 3/87 patients (3.45

) with risk factors and in 1/65 (1.54

) without them (RA 1.91, IC 95

1.88-1.94). We found benign disease in 148 patients (97.37

) and adenocarcinomas in 4 (2.63

), one within a polyp. The 4 adenocarcinomas were detected in postmenopausal women (2 asymptomatic) with endometrial thicknesses equal or greater than 16 mm. The cancer risk was significantly increased in symptomatic (2.36 versus 0.42 in asymptomatic). Three adenocarcinomas were observed between 24 and 48 months of treatment. In conclusion, we suggest an adequate transvaginal ultrasound monitoring of asymptomatic patients treated with TAM, with removal of polyps, because atypia can be present hidden within, considering risk factors and exposure time. We suggest as an acceptable cut-off = 10 mm in asymptomatic postmenopausal patients.