Performance of cervical cytology and HPV testing for primary cervical cancer screening in Latin America: an analysis within the ESTAMPA study.

Background: Cervical cytology remains widely used as the initial tool in cervical cancer screening worldwide. WHO guidelines recommend replacing cytology with primary HPV testing to reach cervical cancer elimination goals. We assessed the performance of cytology and high-risk HPV testing to detect cervical precancer, cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) among women aged 30-64 years participating in the ESTAMPA study. Methods: Women were screened with cytology and HPV across ESTAMPA study centres in Latin America. Screen-positives were referred to colposcopy with biopsy collection and treatment as needed. Those with no evident precancer were recalled at 18-months for a second HPV test to complete disease ascertainment. Performance indicators for cytology and HPV to detect CIN3+ were estimated. Findings: 30,606 participants with available cytology and HPV results were included in the analysis. A total of 440 histologically confirmed CIN3s and 30 cancers were diagnosed. Cytology sensitivity for CIN3+ was 48.5% (95% CI: 44.0-53.0), whereas HPV testing had a sensitivity of 98.1% (95% CI: 96.3-96.7). Specificity was 96.5% (95% CI: 96.3-96.7) using cytology and 88.7% (95% CI: 88.3-89.0) with HPV. Performance estimates varied substantially by study centre for cytology (ranging from 32.1% to 87.5% for sensitivity and from 89.2% to 99.5% for specificity) while for HPV results were more consistent across sites (96.7%-100% and 83.6-90.8%, respectively). Interpretation: The limited and highly variable sensitivity of cytology strongly supports transition to the more robust and reproducible HPV-based cervical screening to ensure progress towards global cervical cancer elimination targets in Latin America. Funding: IARC/WHO, UNDP, HRP/WHO, NCI and local funders.

High sensitivity and specificity rates of cobas® HPV test as a primary screening test for cervical intraepithelial lesions in a real-world setting.

Cervical carcinoma (CC) is the fourth most common malignancy among women. Screening with Papanicolau smear is linked to a reduction in CC incidence rates when screening programs have been developed. However, this technique has several limitations, including moderate sensitivity rates for detection of cervical preneoplastic HPV-related lesions. In this real-world study, we proposed to evaluate the sensitivity and specificity rates of cobas® test, which amplifies target DNA fragments by polymerase chain reaction and hybridization of nucleic acids for the detection of 14 HR-HPV types in a single analysis) used as primary screening test for CC and preneoplastic lesions in women aged 25-65 years in a large University Hospital in Buenos Aires. A total of 1044 patients were included in the sample (median age: 46 years); sensitivity and specificity rates for the HR-HPV test used as primary screening test were 98.66% (95% confidence interval [95CI]: 97.67-99.3%) and 87.15% (95CI: 84.93-89.15%), respectively. The positive predictive value was 88.47% (95CI: 86.54%-90.42%) and the negative predictive value was 98.48% (95CI: 97.75%-99.23%). The cobas® HR-HPV testing was highly sensitive and specific for the detection of CC and preneoplastic lesions in real practice.

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.

Microbiota unbalance in relation to high-risk human papillomavirus cervical infection.

OBJECTIVES: To assess vaginal dysfunction using basic vaginal states and the presence of lactobacillary microbiota in patients with human papillomavirus (HPV) infection with no squamous intra-epithelial lesions (SIL), with low-grade squamous intra-epithelial lesions (L-SIL), and with high-grade squamous intra-epithelial lesions (H-SIL) or squamous cell carcinoma compared with a control group (HPV-negative); to establish the prevalence of bacterial vaginosis, candidiasis, and trichomoniasis in the different age groups; and to characterize the species of lactobacilli according to the type of lesion. METHODS: A cross-sectional study was carried out of patients who underwent clinical examination and collection of vaginal fornixes to study basic vaginal states and culture. Species identification of lactobacilli was performed by mass spectrometry. The results were analyzed using the χ2 and Fisher's tests; p<0.05 was considered significant. High-risk viral types were determined using a multiplex real-time polymerase chain reaction test. RESULTS: A total of 741 patients were analyzed and divided into three age groups: Group 1 aged 18-24 years (n=138), Group 2 aged 25-50 years (n=456), and Group 3 aged >50 years (n=147). All groups were further divided into an HPV-negative (control) group and an HPV-positive group without lesions, with L-SIL, or with H-SIL/squamous cell carcinoma. The prevalence of unbalanced basic vaginal states in patients with H-SIL/squamous cell carcinoma was 72.7% (p=0.03) in Group 1, 53.1% (p=0.05) in Group 2, and no cases of unbalance were detected in Group 3. The prevalence of bacterial vaginosis in women with H-SIL/squamous cell carcinoma in Group 1 was 54.5% and in Group 2 was 43.7%. Patients with H-SIL/squamous cell carcinoma had a prevalence of 21.4% of Lactobacillus crispatus, 42.9% of L. jensenii, and 14.3% of L. iners. CONCLUSIONS: A greater unbalance of vaginal microbiota was observed in patients with SIL, especially in those with H-SIL/squamous cell carcinoma. In this group, an increase in L. jensenii and L. iners compared with control was found. L. crispatus had a similar prevalence to the control group. It is important to characterize the lactobacilli species since the unbalance alters the vaginal microenvironment and acts as a co-factor in the persistence of HPV infection.

Implementing HPV testing in 9 Latin American countries: The laboratory perspective as observed in the ESTAMPA study.

Background: Replacement of cytology screening with HPV testing is recommended and essential for cervical cancer elimination. HPV testing for primary screening was implemented in 12 laboratories within 9 Latin American countries, as part of the ESTAMPA cervical cancer screening study. Our observations provide information on critical operational aspects for HPV testing implementation in diverse resource settings. Methods: We describe the implementation process of HPV testing in ESTAMPA, focusing on laboratory aspects. We assess the readiness of 12 laboratories to start HPV testing and their continuity capacity to maintain good quality HPV testing until end of recruitment or up to December 2021. Readiness was based on a checklist. Information from the study database; regular meetings and monitoring visits; and a questionnaire on laboratory operational aspects sent in May 2020 were used to assess continuity capacity. Compliance with seven basic requirements (readiness) and eight continuity requirements (continuity capacity) was scored (1 = compliant, 0 = not compliant) and totaled to classify readiness and continuity capacity as very limited, limited, moderate or high. Experiences, challenges, and enablers of the implementation process are also described. Results: Seven of 12 laboratories had high readiness, three moderate readiness, and of two laboratories new to HPV testing, one had limited readiness and the other very limited readiness. Two of seven laboratories with high readiness also showed high continuity capacity, one moderate continuity capacity, and the other four showed limited continuity capacity since they could not maintain good quality HPV testing over time. Among three laboratories with moderate readiness, one kept moderate continuity capacity and two reached high continuity capacity. The two laboratories new to HPV testing achieved high continuity capacity. Based on gained expertise, five laboratories have become part of national screening programs. Conclusion: High readiness of laboratories is an essential part of effective implementation of HPV testing. However, high readiness is insufficient to guarantee HPV testing high continuity capacity, for which a "culture of quality" should be established with regular training, robust monitoring and quality assurance systems tailored to local context. All efforts to strengthen HPV laboratories are valuable and crucial to guarantee effective implementation of HPV-based cervical screening.

Multicentric study of cervical cancer screening with human papillomavirus testing and assessment of triage methods in Latin America: the ESTAMPA screening study protocol.

INTRODUCTION: Human papillomavirus (HPV) testing is replacing cytology in primary screening. Its limited specificity demands using a second (triage) test to better identify women at high-risk of cervical disease. Cytology represents the immediate triage but its low sensitivity might hamper HPV testing sensitivity, particularly in low-income and middle-income countries (LMICs), where cytology performance has been suboptimal. The ESTAMPA (EStudio multicéntrico de TAMizaje y triaje de cáncer de cuello uterino con pruebas del virus del PApiloma humano; Spanish acronym) study will: (1) evaluate the performance of different triage techniques to detect cervical precancer and (2) inform on how to implement HPV-based screening programmes in LMIC. METHODS AND ANALYSIS: Women aged 30-64 years are screened with HPV testing and Pap across 12 study centres in Latin America. Screened positives have colposcopy with biopsy and treatment of lesions. Women with no evident disease are recalled 18 months later for another HPV test; those HPV-positive undergo colposcopy with biopsy and treatment as needed. Biological specimens are collected in different visits for triage testing, which is not used for clinical management. The study outcome is histological high-grade squamous intraepithelial or worse lesions (HSIL+) under the lower anogenital squamous terminology. About 50 000 women will be screened and 500 HSIL+ cases detected (at initial and 18 months screening). Performance measures (sensitivity, specificity and predictive values) of triage techniques to detect HSIL+ will be estimated and compared with adjustment by age and study centre. ETHICS AND DISSEMINATION: The study protocol has been approved by the Ethics Committee of the International Agency for Research on Cancer (IARC), of the Pan American Health Organisation (PAHO) and by those in each participating centre. A Data and Safety Monitoring Board (DSMB) has been established to monitor progress of the study, assure participant safety, advice on scientific conduct and analysis and suggest protocol improvements. Study findings will be published in peer-reviewed journals and presented at scientific meetings. TRIAL REGISTRATION NUMBER: NCT01881659.

Human Papillomavirus Types Involved in External Genital Warts in a Group of Argentinian Women in Buenos Aires.

OBJECTIVES: The aim of the study was to understand which human papillomavirus (HPV) types are involved in external genital warts (GWs) in a group of Argentinian women in Buenos Aires. METHODS: One hundred sixty consecutive women 15 to 45 years old with GWs were enrolled. All patients underwent confirmatory biopsy. In 150 of 160 patients, the diagnosis of GWs was confirmed by histology, DNA-HPV was investigated using polymerase chain reaction, and sequence analysis with generic primers MY09/11 was performed. RESULTS: HPV 6 and/or 11 was detected in 93.3% patients (140/150). HPV 6 was by far the most common type (80%), followed by HPV 11 (12.7%). Coinfection with these 2 types occurred in 0.7%. HPV 16 was found in 2% and HPV 73 in 0.7%. CONCLUSION: HPV 6 and/or 11 are present in 93.3% (95% confidence interval, 0.9-1.0) of external genital warts in a group of Argentinian women in Buenos Aires and, therefore, could be prevented with HPV vaccine (NCT 015998779).

Anal intraepithelial lesions in women with human papillomavirus-related disease.

OBJECTIVE: This study aimed to determine the prevalence of anal intraepithelial lesions in women with histologic diagnosis of intraepithelial lesions of the lower genital tract. MATERIALS AND METHODS: This was a cross-sectional study conducted at the Lower Genital Tract and Colposcopy Unit of Hospital de Clínicas "José de San Martín," University of Buenos Aires, Argentina. A total of 481 women with histologically confirmed low-grade and high-grade cervical, vaginal, or vulvar intraepithelial lesions were evaluated between 2005 and 2011. They were referred for cytologic samples and examination with high-resolution anoscopy. We obtained biopsy specimens of any suspicious colposcopic images. RESULTS: Of a total of 481 patients, 404 (84%) were immunocompetent, 31 (6.4%) were HIV+, and 46 (9.6%) had other causes of immunosuppression. Moreover, of the 481 patients, 134 (27.86%) had anal intraepithelial neoplasia (AIN); 28 (5.82%) had high-grade AIN and 106 (22%) had low-grade AIN. Women with high-grade cervical intraepithelial neoplasia (CIN 2, 3) had 2 times the odds of developing AIN compared with women with low-grade CIN (CIN 1) (odds ratio = 1.91, 95% confidence interval = 1.1-3.6). Regarding localization, we found statistically significant difference between the frequency of vulvar and anal lesions. Women with vulvar condylomata and vulvar intraepithelial neoplasia (VIN) may be more likely to develop AIN. CONCLUSIONS: Immunocompetent women with CIN, vaginal intraepithelial neoplasia, or VIN may also present high-grade or low-grade anal intraepithelial lesions so we should consider AIN as part of multicentric disease of the lower genital tract. Cervical intraepithelial neoplasia, VIN, condyloma accuminatta, and vaginal intraepithelial neoplasia could be warning signs of anal intraepithelial lesions.

Tratamiento quirúrgico de las lesiones anales intra-epiteliales (AIN) de alto grado / Surgical treatment of high grade intraepitelial anal lesions (AIN)

Introducción: La incidencia del Cáncer de ano se encuentra en aumento tanto en pacientes HIV positivos o inmunosuprimidos como en los inmunocompetentes. Éste se asocia a la infección por HPV, con un comportamiento similar al del desarrollo del cáncer de cuello uterino, a través de la producción de lesiones intra-epiteliales escamosas (SIL). Para su diagnóstico se utiliza la anoscopía de alta resolución. Su tratamiento es aún controversial. Objetivo: Presentamos nuestra experiencia en el tratamiento quirúrgico de lesiones intra-epiteliales anales de alto grado (AIN III) guiadas con anoscopía de alta resolución. Lugar de aplicación o marco de referencia: Hospital Universitario. Diseño: Estudio retrospectivo. Material y métodos: Realizamos una revisión de los pacientes diagnosticados y operados (escisión/cauterización de las lesiones visualizadas con anoscopia de alta resolución) con diagnóstico de lesiones anales intra-epiteliales de alto grado (AIN III) en el marco del Programa de Prevención, Diagnóstico, Terapéutica y Vacunación en Patología del Tracto Genital Inferior del Hospital de Clínicas de Buenos Aires "José de San Martín". Resultados: A las pacientes con antecedentes de infección por HPV en el tracto genital inferior, se las evaluó con anoscopía magnificada. Entre enero de 2005 y agosto de 2010, se estudiaron 305 pacientes (32 inmunosuprimidas). De éstas, 18 (5.9%) presentaron lesiones intra-epiteliales de alto grado (AIN III) confirmadas por histología. Las mismas fueron remitidas para tratamiento quirúrgico. Tres eran inmunosuprimidas, dos por HIV. La edad media fue de 34 años (19-63 años). El seguimiento medio fue de 15 meses, 4 a 39 meses. Se produjo una recurrencia a los 4 meses. Ningún paciente desarrolló incontinencia, estenosis, infección postoperatoria, o hemorragia significativa después del tratamiento quirúrgico... (TRUNCADO)

Introduction: Over the last decades, anal cancer incidence rose to an epidemic range in general population and in some risk groups like inmuno-supressed or HIV patients. Anal cancer develops from squamous intraepithelial lesion (SIL) in the anal transitional zone produced by HPV infection. High resolution anoscopy is used to diagnose these dysplastic changes. There is no consensus about the best treatment option for high grade anal intraepithelial neoplasia (AIN III). Objective: To report our experience in the treatment of high grade anal intraepithelial neoplasia targeted by high resolution anoscopy. Design: Retrospective study. Material and method: Patients diagnose and treated for AIN III in the "Prevention, Diagnosis, Treatment and Vaccination of the Inferior Genital Tract" Program of the Hospital de Clínicas de Buenos Aires "José de San Martín". Results: Patients with history of HPV disease in the genital tract were studied with high resolution anoscopy. 305 patients (32 inmunosupressed) were studied between January of 2005 and August of 2010. 18 (5.9%) had AIN III and were surgically treated. Mean age was 34 years (19-63). Mean follow-up was 15 months (4 to 39). We observed one recurrenee at 4 month. No complications were present. Conclusions: High resolution anoscopy targeted surgery AIN III is feasible and seams to eradicate these lesions in the inmunocompetent patient.

Association of DRB1 and DQB1 HLA class II polymorphisms in high-grade and neoplastic cervical lesions of women from Argentina.

OBJECTIVES: To investigate associations between HLA-DRB1 and HLA-DQB1 polymorphisms with low- and high-grade cervical lesions in Argentine population and the role human papillomavirus status in these associations. MATERIALS AND METHODS: Cervical biopsies and peripheral blood samples were taken from 32 patients with cervical intraepithelial neoplasia grade 1 (CIN 1) and 44 patients with cervical CIN 3 or invasive squamous cell carcinomas. Cervical cells and peripheral blood samples from 40 healthy women were included as control group. Human papillomavirus detection and typing were done by polymerase chain reaction (PCR) MY09, 11-restriction fragment length polymorphisms, or PCR 5+, 6+ dot-blot hybridization, and HLA DR/DQ typing by the PCR-sequence-specific oligonucleotide probes method. RESULTS: HLA-DRB1*04 and HLA-DQB1*0302 were found to be positive associated with the CIN 3/invasive squamous cell carcinomas subgroup, whereas HLA-DRB1*13 and HLA-DQB1*02 were negatively associated with the same group, when comparing to the control group. CONCLUSIONS: The data support the hypothesis that HLA-DRB1*04 and HLA-DQB1*0302 may be considered risk factors for malignant progression, whereas HLA-DRB1*13 and HLA-DQB1*02 may have a protective role. Further studies with a larger group are needed to confirm these susceptibility and protective roles in disease progression in Argentine population.

Utilidad de la anoscopía magnificada en la detección de lesiones preneoplásicas por HPV / High resolution anoscopy in the detection of HPV-pre-neoplasic lesions

El cáncer de anal es infrecuente, aunque su incidencia está aumentando. El HPV se asocia a su desarrollo a través de las lesiones intraepiteliales escamosas (SIL). Se propone la citología anal y la anoscopía magnificada, con técnica de colposcopía, para la detección de estas lesiones.

Es posible realizar tratamiento conservador en el microcarcinoma de cuello uterino estadio Ia1? / Is possible to make preservative treatment in the microcarcinoma of uterine cervix stage Ia1?

El objetivo del presente trabajo es valorar la conización cervical como único tratamiento del microcarcinoma del cuello uterino estadío Ia1 en pacientes jóvenes con deseos de fertilidad. La nomenclatura ha sido modificada en varias oportunidades en el transcurso de los años, hecho que dificulta tener un criterio único de estadificación y tratamiento aceptado internacionalmente. Estas modificaciones han surgido de la crítica que han realizado distintos autores, desde la aparición de la primera definición en el año 1947; con el objetivo de evaluar el tamaño tumoral que pueda tratarse con terapéuticas conservadoras. Sabemos que cuando aumenta la profundidad de invasión, mayor es el porcentaje de ganglios linfáticos comprometidos con altas tasas de recurrencia y muerte. Es por ello que realizamos una revisión de los casos tratados en la 1º Cátedra de Ginecología del Hospital de Clínicas "José de San Martín" entre los años 1975 a 1999, evaluando los procedimientos diagnósticos utilizados preterapéuticamente: citología, colposcopía, biopsias exo y endocervicales, y el procesamiento efectuado de las piezas de conización cervical para realizar una correcta estadificación. Sobre el total de 65 casos evaluados en dicho período sólo 15 fueron tratados mediante conización cervical (23 por ciento), con un seguimiento que oscila entre 2 y 9 años. El 75 por ciento de estos casos poseían una invasión menor de 1 mm y el 25 por ciento restante presentaban una invasión entre 1 y 3 mm. Ninguno de los casos en donde fue realizada una conización cervical como única terapéutica presentó recurrencias y/o muertes durante el período de seguimiento. Los criterios de selección utilizados fueron los siguientes: 1) adecuado procesamiento del cono para su correcta interpretación histopatológica y estadificación; 2) ausencia de invasión linfática y vascular, o de invasión confluente en la pieza quirúrgica; 3) sección quirúrgica del cono con 3 bordes libres; es mandatorio que el vértice del cono no esté comprometido; 4) deseos de preservar la fertilidad de la paciente y consentimiento informado; 5) posibilidad de seguimiento. Es por ello que basados en la evidencia de nuestra propia casuística y en la de otros autores consideramos factible realizar en los microcarcinomas de cuello uterino estadío Ia1 que cumplan con los enunciados anteriormente mencionados conizaciones cervicales como única terapéutica. (AU)

Es posible realizar tratamiento conservador en el microcarcinoma de cuello uterino estadio Ia1? / Is possible to make preservative treatment in the microcarcinoma of uterine cervix stage Ia1?

El objetivo del presente trabajo es valorar la conización cervical como único tratamiento del microcarcinoma del cuello uterino estadío Ia1 en pacientes jóvenes con deseos de fertilidad. La nomenclatura ha sido modificada en varias oportunidades en el transcurso de los años, hecho que dificulta tener un criterio único de estadificación y tratamiento aceptado internacionalmente. Estas modificaciones han surgido de la crítica que han realizado distintos autores, desde la aparición de la primera definición en el año 1947; con el objetivo de evaluar el tamaño tumoral que pueda tratarse con terapéuticas conservadoras. Sabemos que cuando aumenta la profundidad de invasión, mayor es el porcentaje de ganglios linfáticos comprometidos con altas tasas de recurrencia y muerte. Es por ello que realizamos una revisión de los casos tratados en la 1º Cátedra de Ginecología del Hospital de Clínicas "José de San Martín" entre los años 1975 a 1999, evaluando los procedimientos diagnósticos utilizados preterapéuticamente: citología, colposcopía, biopsias exo y endocervicales, y el procesamiento efectuado de las piezas de conización cervical para realizar una correcta estadificación. Sobre el total de 65 casos evaluados en dicho período sólo 15 fueron tratados mediante conización cervical (23 por ciento), con un seguimiento que oscila entre 2 y 9 años. El 75 por ciento de estos casos poseían una invasión menor de 1 mm y el 25 por ciento restante presentaban una invasión entre 1 y 3 mm. Ninguno de los casos en donde fue realizada una conización cervical como única terapéutica presentó recurrencias y/o muertes durante el período de seguimiento. Los criterios de selección utilizados fueron los siguientes: 1) adecuado procesamiento del cono para su correcta interpretación histopatológica y estadificación; 2) ausencia de invasión linfática y vascular, o de invasión confluente en la pieza quirúrgica; 3) sección quirúrgica del cono con 3 bordes libres; es mandatorio que el vértice del cono no esté comprometido; 4) deseos de preservar la fertilidad de la paciente y consentimiento informado; 5) posibilidad de seguimiento. Es por ello que basados en la evidencia de nuestra propia casuística y en la de otros autores consideramos factible realizar en los microcarcinomas de cuello uterino estadío Ia1 que cumplan con los enunciados anteriormente mencionados conizaciones cervicales como única terapéutica.