A Comprehensive Program to Improve Treatment of Precancerous Cervical Lesions in the Rio Grande Valley of Texas.

OBJECTIVE: To assess the impact of a multicomponent intervention in women with cervical dysplasia who were treated with loop electrosurgical excision procedure (LEEP), as well as the time between colposcopy and treatment. DESIGN: Retrospective cohort study. INTERVENTION: Clinic participation in a multicomponent cervical cancer prevention program that included community outreach, patient in-reach, and navigation, as well as provider capacity building with in-person training and ongoing telementoring through Project ECHO. MAIN OUTCOME MEASURES: Medical records were reviewed to evaluate women with cervical dysplasia undergoing treatment with LEEP within 90 days of colposcopy, as well as time between colposcopy and treatment. Baseline data from year 1 were compared with each subsequent year of implementation. Additional variables examined included patient's age, history of abnormal screening results, and percentage of families living below poverty line based on county of residence, parity, and clinic site. We performed logistic regression and multiple linear regression analyses to assess the programmatic impact in the outcomes of interest by year of program implementation. RESULTS: A total of 290 women were included in the study. The proportion of women undergoing treatment within 90 days of colposcopy increased from 76.2% at baseline to 91.3% in year 3 and 92.9% in year 4 of program implementation. The odds of undergoing treatment within 90 days were 5.11 times higher in year 4 of program implementation than at baseline. The mean time between colposcopy and LEEP decreased from 62 days at baseline to 45 days by year 4 of program implementation. CONCLUSIONS: Implementation of our multicomponent cervical cancer prevention program increased the proportion of women undergoing LEEP within 90 days of colposcopy and decreased the time between colposcopy and LEEP. This program has the potential to support cervical cancer prevention efforts and could be implemented in other low-resource settings.

The Mulher Study: cervical cancer screening with primary HPV testing in Mozambique.

OBJECTIVE: To evaluate cervical cancer screening with primary human papillomavirus (HPV) testing in Mozambique, a country with one of the highest burdens of cervical cancer globally. METHODS: Women aged 30-49 years were prospectively enrolled and offered primary HPV testing using either self-collected or provider-collected specimens. Patients who tested positive for HPV underwent visual assessment for treatment using visual inspection with acetic acid to determine eligibility for thermal ablation. If ineligible, they were referred for excision with a loop electrosurgical excision procedure, for cold knife conization, or for cervical biopsy if malignancy was suspected. RESULTS: Between January 2020 and January 2023, 9014 patients underwent cervical cancer screening. Median age was 37 years (range 30-49) and 4122 women (45.7%) were patients living with HIV. Most (n=8792, 97.5%) chose self-collection. The HPV positivity rate was 31.1% overall and 39.5% among patients living with HIV. Of the 2805 HPV-positive patients, 2588 (92.3%) returned for all steps of their diagnostic work-up and treatment, including ablation (n=2383, 92.1%), loop electrosurgical excision procedure (n=169, 6.5%), and cold knife conization (n=5, 0.2%). Thirty-one patients (1.2%) were diagnosed with cancer and referred to gynecologic oncology. CONCLUSION: It is feasible to perform cervical cancer screening with primary HPV testing and follow-up in low-resource settings. Participants preferred self-collection, and the majority of screen-positive patients completed all steps of their diagnostic work-up and treatment. Our findings provide important information for further implementation and scale-up of cervical cancer screening and treatment services as part of the WHO global strategy for the elimination of cervical cancer.

Conservative Treatment of Stage IA1 Cervical Carcinoma Without Lymphovascular Space Invasion: A 20-year Retrospective Study in Brazil.

PURPOSE: To evaluate recurrence rates and risk factors among women with stage IA1 cervical cancer without lymph vascular space invasion managed conservatively. METHODS: retrospective review of women with stage IA1 squamous cervical cancer who underwent cold knife cone or loop electrosurgical excision procedure, between 1994 and 2015, at a gynecologic oncology center in Southern Brazil. Age at diagnosis, pre-conization findings, conization method, margin status, residual disease, recurrence and survival rates were collected and analyzed. RESULTS: 26 women diagnosed with stage IA1 squamous cervical cancer without lymphovascular space invasion underwent conservative management and had at least 12 months follow-up. The mean follow-up was 44.6 months. The mean age at diagnosis was 40.9 years. Median first intercourse occurred at age 16 years, 11.5% were nulliparous and 30.8% were current or past tobacco smokers. There was one Human immunodeficiency virus positive patient diagnosed with cervical intraepithelial neoplasia grade 2 at 30 months after surgery. However, there were no patients diagnosed with recurrent invasive cervical cancer and there were no deaths due to cervical cancer or other causes in the cohort. CONCLUSION: Excellent outcomes were noted in women with stage IA1 cervical cancer without lymphovascular space invasion and with negative margins who were managed conservatively, even in a developing country.

OBJETIVO: Avaliar recidiva e seus fatores de risco em mulheres com câncer do colo do útero estádio IA1 sem invasão do espaço linfovascular tratadas conservadoramente. MéTODOS:: Estudo de coorte retrospectivo de pacientes com câncer do colo do útero IA1 escamoso submetidas a cone do colo do útero, entre 1994 e 2015, em um centro de ginecologia oncológica do sul do Brasil. Foram revisados e analisados idade no diagnóstico, achados pré-conização, método de conização, margens, doença residual, recorrência e sobrevida. RESULTADOS: 26 mulheres diagnosticadas com câncer do colo do útero estádio escamoso sem invasão do espaço linfovascular foram submetidas a tratamento conservador, com seguimento mínimo de 12 meses. O tempo médio de seguimento foi 44,6 meses. A média de idade no diagnóstico foi 40,9 anos. A primeira relação sexual ocorreu aos 16 anos (mediana), 11,5% eram nulíparas e 30,8% eram tabagistas atuais ou passadas. Houve um caso de recidiva de neoplasia intraepitelial cervical grau 2 aos 30 meses em uma paciente com vírus da imunodeficiência humana. Não houve pacientes diagnosticados com câncer de colo do útero invasor recorrente, e não houve mortes por câncer do colo do útero ou outras causas. CONCLUSãO:: Os resultados observados após tratamento conservador em mulheres com câncer cervical escamoso IA1 sem invasão do espaço linfovascular com margens negativas foram excelentes, mesmo em um país em desenvolvimento.

Conservative Treatment of Stage IA1 Cervical Carcinoma Without Lymphovascular Space Invasion: A 20-year Retrospective Study in Brazil / Tratamento conservador do câncer do colo do útero IA1 sem invasão linfovascular: estudo retrospectivo no Brasil

Abstract Purpose: To evaluate recurrence rates and risk factors among women with stage IA1 cervical cancer without lymph vascular space invasion managed conservatively. Methods: retrospective review of women with stage IA1 squamous cervical cancer who underwent cold knife cone or loop electrosurgical excision procedure, between 1994 and 2015, at a gynecologic oncology center in Southern Brazil. Age at diagnosis, pre-conization findings, conization method, margin status, residual disease, recurrence and survival rates were collected and analyzed. Results: 26 women diagnosed with stage IA1 squamous cervical cancer without lymphovascular space invasion underwent conservative management and had at least 12 months follow-up. The mean follow-up was 44.6 months. The mean age at diagnosis was 40.9 years. Median first intercourse occurred at age 16 years, 11.5% were nulliparous and 30.8% were current or past tobacco smokers. There was one Human immunodeficiency virus positive patient diagnosed with cervical intraepithelial neoplasia grade 2 at 30 months after surgery. However, there were no patients diagnosed with recurrent invasive cervical cancer and there were no deaths due to cervical cancer or other causes in the cohort. Conclusion: Excellent outcomes were noted in women with stage IA1 cervical cancer without lymphovascular space invasion and with negative margins who were managed conservatively, even in a developing country.

Resumo Objetivo: Avaliar recidiva e seus fatores de risco em mulheres com câncer do colo do útero estádio IA1 sem invasão do espaço linfovascular tratadas conservadoramente. Métodos: Estudo de coorte retrospectivo de pacientes com câncer do colo do útero IA1 escamoso submetidas a cone do colo do útero, entre 1994 e 2015, em um centro de ginecologia oncológica do sul do Brasil. Foram revisados e analisados idade no diagnóstico, achados pré-conização, método de conização, margens, doença residual, recorrência e sobrevida. Resultados: 26 mulheres diagnosticadas com câncer do colo do útero estádio escamoso sem invasão do espaço linfovascular foram submetidas a tratamento conservador, com seguimento mínimo de 12 meses. O tempo médio de seguimento foi 44,6 meses. A média de idade no diagnóstico foi 40,9 anos. A primeira relação sexual ocorreu aos 16 anos (mediana), 11,5% eram nulíparas e 30,8% eram tabagistas atuais ou passadas. Houve um caso de recidiva de neoplasia intraepitelial cervical grau 2 aos 30 meses em uma paciente com vírus da imunodeficiência humana. Não houve pacientes diagnosticados com câncer de colo do útero invasor recorrente, e não houve mortes por câncer do colo do útero ou outras causas. Conclusão: Os resultados observados após tratamento conservador em mulheres com câncer cervical escamoso IA1 sem invasão do espaço linfovascular com margens negativas foram excelentes, mesmo em um país em desenvolvimento.

Hands-On Training Courses for Cervical Cancer Screening, Diagnosis, and Treatment Procedures in Low- and Middle-Income Countries.

In 2018, there were approximately 570,000 new cases of cervical cancer worldwide. More than 85% of cases occurred in low- and middle-income countries (LMICs), primarily because of poor access to screening and a limited number of medical providers trained to diagnose and treat cervical precancerous lesions. Our objective was to provide locally arranged, hands-on training courses for medical providers in LMICs to learn to perform cervical cancer screening, diagnosis, and treatment procedures. The courses included didactic lectures and hands-on training stations using low-cost simulation models developed by bioengineers and students at Rice University in Houston, TX, United States, and the Malawi Polytechnic in Blantyre, Malawi. The hands-on training stations included visual inspection with acetic acid (VIA), colposcopy, cervical biopsy, endocervical curettage, loop electrosurgical excision procedure (LEEP), and thermal ablation. Provider pre- and postcourse confidence levels in performing the procedures were evaluated. From February 2017 to January 2020, we arranged 15 hands-on training courses in seven cities across six countries (El Salvador, Mozambique, Trinidad and Tobago, Lesotho, Malawi, and Nepal). Overall, there were 506 participants. The average number of participants per course was 38 (range 19-92). The participants included doctors, nurses, and midwives. The course duration varied from 1 to 3 days. Increased confidence in performing VIA, colposcopy and cervical biopsy, ablation, and LEEP was reported by 69%, 71%, 61%, and 76% of participants, respectively. Our findings suggest that locally arranged, hands-on cervical cancer prevention training courses in LMICs can improve provider confidence in performing cervical cancer screening, diagnosis, and treatment procedures. These courses are part of a larger strategy to build local capacity for delivering and improving cervical cancer prevention services in LMICs.

American Society of Clinical Oncology (ASCO) Cervical Cancer Prevention Program: A Hands-On Training Course in Nepal.

Cervical cancer is the leading cause of death among women in Nepal. The American Society of Clinical Oncology (ASCO) and The University of Texas MD Anderson Cancer Center collaborated with international and local experts to hold a cervical cancer prevention course in Nepal in November 2019. The course included didactic lectures and a hands-on workshop. The didactic lectures included the epidemiology of cervical cancer globally and locally, cervical cancer screening guidelines, human papillomavirus vaccination, colposcopy and visual inspection with acetic acid (VIA), cervical dysplasia, and cervical cancer treatment. The hands-on workshop consisted of four stations: (1) VIA; (2) colposcopy, cervical biopsy, and endocervical curettage; (3) thermal ablation; and (4) loop electrosurgical excision procedure (LEEP). A train-the-trainer model short course was held by the international faculty to assist six local faculty to become familiar with the instruments, procedures, and models used in the hands-on training stations. Forty-two people (84% gynecologist, 8% radiation oncologist, and 8% other) attended the course. Following the course, the international faculty visited the regional hospitals for additional educational activities. Increased knowledge in cervical cancer screening guidelines and ability in performing VIA, colposcopy and cervical biopsy, thermal ablation, and LEEP were reported by 89%, 84%, 84%, 87%, and 84% of participants, respectively, from the postcourse on-site evaluations. From the 6-month follow-up survey, all respondents reported that they had made practice changes based on what they learned in the course and had implemented or tried to implement the cervical cancer screening guidelines presented at the course. In conclusion, the course evaluations suggested an improvement in participants' ability to perform cervical cancer screening and diagnostic procedures and reported the changes in practices after training.

Cervical cancer screening abnormalities in immunosuppressed renal transplant women: case-control study in Southern Brazil.

PURPOSE: To evaluate the prevalence of cervical pre-malignancies in the cervical cytology of female renal transplant recipients (RTR) and compare to immunocompetent patients. METHODS: A prospective case-control study of 165 RTR (cases) and 372 immunocompetent women (controls) was carried out from May 2015 to August 2016. The participants completed a questionnaire with demographic characteristics, habits, reproductive history, and information about the renal transplant. Cervical cytology samples were collected at their visit for cervical cancer screening. Relevant medical history was obtained from medical records and previous cervical cytology results were retrieved: from the time of kidney transplantation to the beginning of this study for RTR and all collected throughout life for controls. RESULTS: The mean age was similar between groups (42.6 ± 11.4 vs. 41.8.2 ± 11.1 years, p = 0.447). Considering cervical cytology collected since the kidney transplant, RTR had three times higher rates of abnormal cervical cytology test (24.8% of RTR vs. 6.3% for controls), and the abnormalities were more frequent (p < 0.001) for low squamous intraepithelial lesion (LSIL) (n = 23, 13.9%) and high squamous intraepithelial lesion (HSIL) (n = 9, 5.5%). Cervical cytology collected during the study had normal results in 152 RTR (92.1%) vs. 326 controls (93.9%) (p > 0.05). When the altered results were broken down, a higher frequency of LSIL could be seen in RTR (3.6% vs 0.0%, p = 0.008). CONCLUSION: RTR had significantly higher rates of cervical cytology abnormalities comparing to the control group and most of it was composed of LSIL.

Pelvic Insufficiency Fractures After External Beam Radiation Therapy for Gynecologic Cancers: A Meta-analysis and Meta-regression of 3929 Patients.

PURPOSE: To estimate the overall rate, symptomatic proportion, and most common sites of pelvic insufficiency fracture (PIF) after external beam radiation therapy for gynecologic cancers based on posttreatment computed tomography, magnetic resonance imaging, positron emission tomography, or bone scintigraphy. METHODS AND MATERIALS: A systematic search of databases (PubMed and EMBASE) was performed (CRD42019125679). The pooled summary of overall PIF and the proportion of symptomatic cases were calculated using the random-effects model weighted by the inverse variance. A multivariate meta-regression was performed to evaluate potential sources of heterogeneity regarding PIF fractures. RESULTS: Twenty-one studies met the inclusion criteria (total 3929 patients). Five hundred four patients developed PIF, translating to an overall rate of 14% (95% confidence interval, 10%-18%, based on 21 studies). Among these cases with PIF, the proportion of symptomatic patients was 61% (95% confidence interval, 52%-69%, based on 14 studies). The total number of PIFs was 704 (mean, 1.72 PIFs per each patient to develop PIF, based on 14 studies). More recent series (P = .0074) and the use of intensity modulated radiation therapy (P = .0299) were associated with lower fracture rates. The most common fracture sites were sacroiliac joint (39.7%), body of the sacrum (33.9%), pubis (13%), lumbar vertebra (7%), iliac bone (2.8%), acetabulum (2.1%), and femoral head/neck (1.5%). The median time to fracture was 7.1 to 19 months after radiation therapy. CONCLUSIONS: The incidence of PIF after radiation therapy for gynecologic cancers is high (14%), with the majority affecting the sacral bone or joint (73.6%), although this risk appears to be lower with intensity modulated radiation therapy. Posttreatment bone surveillance is warranted in this population because nearly 40% of patients were asymptomatic at the time of PIF diagnosis.

Perineural invasion (PNI) in vulvar carcinoma: A review of 421 cases.

OBJECTIVES: To evaluate the prevalence and associated prognostic indicators in patients with vulvar carcinoma with and without evidence of perineural invasion (PNI). METHODS: A retrospective review identified 421 patients with invasive vulvar carcinoma evaluated at a single institution between 1993 and 2011. Medical records were reviewed for demographic data, pathologic information and presence or absence of PNI, treatment type, and recurrence/outcome information. Variables were compared between patients with PNI to those without PNI. RESULTS: Of the 421 patients included in the study, 32 (7.6%) had tumors with PNI. There were no significant differences in age, race/ethnicity, smoking history, histologic subtype, or grade between the group of patients with PNI and the group without PNI. The group with PNI was more likely to have lichen sclerosus (25.0% vs. 15.4%, p = 0.024), stage III/IV disease (59.4% vs. 36.0%, p = 0.007), lymph node involvement (50.0% vs. 21.6%, p = 0.002), and lymphovascular space invasion (LVSI) (53.1% vs. 15.9%, p < 0.001). A higher proportion of patients in the PNI group underwent primary or adjuvant radiation therapy (68.8% vs. 45.0%, p = 0.016). The median follow-up was 67.1 months (range < 1.0 to 284.3). Patients with PNI had significantly shorter overall survival (OS), median 25.5 vs. 94.3 months (p < 0.001), and progression-free survival (PFS), median 17.5 vs. 29.0 months (p = 0.004). After adjusting for stage, patients with PNI had a greater risk for death and progression (OS: hazard ratio, 2.71; p < 0.001; PFS: hazard ratio, 1.64; p-value = 0.020). CONCLUSION: PNI should be considered an independent poor prognostic factor for patients with vulvar carcinoma, and should be included as part of the pathologic analysis.

Paget's disease of the vulva: A review of 89 cases.

The purpose of this study was to retrospectively review the clinical characteristics and outcomes of a series of women with Paget's disease of the vulva. A retrospective review was performed of 89 women with Paget's disease of the vulva evaluated at a single institution between 1966 and 2010. Medical records were reviewed for demographic information, clinical data, pathologic findings, treatment modalities and outcomes. We found that the primary treatment was surgery for 74 (83.1%) patients, with positive margins noted in 70.1% of cases. Five patients (5.6%) underwent topical treatment with imiquimod and/or 5-fluorouracil, one patient (1.1%) underwent laser ablation and treatment was unknown in 9 patients (10.1%). The majority of patients had multiple recurrences, with 18% having four or more recurrences. There were no significant differences in recurrence rates between patients who underwent surgery and those who did not. Furthermore, there was no association between positive margins following primary surgery and recurrence. Forty-one patients (46.1%) were diagnosed with 53 synchronous or metachronous cancers. Seven patients (7.9%) were found to have invasive vulvar cancer with 1 mm or more depth of invasion, but none of the patients died of Paget's disease or associated vulvar/vaginal cancer. Our findings suggest that the majority of patients with Paget's disease of the vulva develop multiple recurrences regardless of treatment modality or margin status. Alternatives to surgery are needed to better care for women with this disease.

Carcinoma of the Bartholin Gland: A Review of 33 Cases.

OBJECTIVE: Primary carcinoma of the Bartholin gland is a rare malignancy that accounts for approximately 5% of vulvar carcinomas. The aim of the study was to compare the outcomes of women with primary Bartholin gland carcinoma (BGC) with those with non-Bartholin gland-related vulvar carcinoma. MATERIALS AND METHODS: A retrospective chart review of 429 patients with invasive vulvar carcinoma evaluated at a single institution between 1993 and 2011 was performed. Medical records were reviewed for demographic data, pathologic information, treatment type, and recurrence/outcome information. These variables were compared between patients with primary BGC and patients with non-Bartholin gland-related vulvar carcinoma. RESULTS: Thirty-three (7.7%) of the 429 patients with invasive vulvar carcinoma had primary carcinoma of the Bartholin gland. Twenty-nine patients (87.9%) had squamous cell histology and 4 patients (12.1%) had adenocarcinoma. When compared with non-Bartholin gland-related vulvar carcinoma, patients with primary BGC had a younger age at diagnosis (median, 57 vs 63 years; P = 0.045), had a higher rate of stage III/IV disease (60.6% vs 35.8%; P = 0.008), and were more likely to receive radiation therapy (78.8% vs 43.9%; P < 0.001). However, there were no significant differences between the 2 groups with regard to histologic subtype, lymphovascular space involvement, perineural invasion, positive margins, recurrence-free survival, or overall survival. CONCLUSIONS: Despite being diagnosed at a more advanced stage, patients with primary carcinoma of the Bartholin gland seem to have similar oncologic outcomes and survival rates to patients with non-Bartholin gland-related vulvar carcinoma.

High-Grade Cervical Dysplasia following Radiation Therapy for Invasive Cervical Cancer: A Report of Four Cases.

INTRODUCTION: The standard treatment for locally advanced cervical cancer is chemoradiation, with the majority of patients having a complete response to the therapy. The current surveillance recommendations from the Society of Gynecologic Oncology include annual cytology, with a small proportion of patients subsequently diagnosed with high-grade cervical dysplasia (CIN 2/3). To date, there is limited information regarding the optimal treatment and outcome for patients diagnosed with CIN 2/3. The current report describes the diagnosis, management and outcome of 4 patients diagnosed with CIN 2/3 following chemoradiation. CASE DESCRIPTION: We describe 4 patients who developed CIN 2/3 seven months to 8 years following radiation therapy for locally advanced cervical cancer. All 4 patients were asymptomatic and the abnormalities were first detected by a Pap test. Three of the patients were managed conservatively with observation, and the CIN 2/3 resolved without intervention. One patient underwent 2 cervical conizations followed by a hysterectomy with no residual dysplasia noted on the hysterectomy specimen. CONCLUSION: The majority of patients with recurrent cervical cancer after chemoradiation are symptomatic, and most cases are detected by a physical examination. The role of cytology, colposcopy and biopsies may be of limited value. Furthermore, the significance of the diagnosis of CIN 2/3 in patients previously treated with radiation therapy was not associated with recurrent disease in the 4 patients described. Our results suggest that cytology may be of limited value in detecting recurrence in patients following radiation therapy, even when CIN 2/3 is detected.