Melissa Lopez Varon

Addressing the cervical cancer burden in the Rio Grande Valley of Texas through a multi-component program to improve screening and diagnostic follow-up: A retrospective cohort study

Cervical cancer is preventable by following guidelines for vaccination, screening, diagnosis and treatment of preinvasive cervical lesions. We implemented a multicomponent intervention to increase rates of colposcopy after abnormal screening results in three clinic systems in the Rio Grande Valley, along the Texas-Mexico border. The goal of this study was to assess the outcomes of this program including participation in colposcopy within 90 days of screening for women with abnormal screening results, and the time between screening and colposcopy appointments during the first year (Year 1/baseline) and subsequent years (Years 2 through 4) of program implementation. We performed a retrospective cohort analysis of medical records of clinics participating in the program. We utilized multiple logistic regression and linear regression to assess the colposcopic outcomes of women with indication for colposcopy. A total of 1556 of the 14,846 (10.5 %) women who had undergone cervical cancer screening had abnormal results and met the criteria to be referred for colposcopy. There was a significant increase in the proportion of women who underwent colposcopy (within 90 days of screening) from Year 1/baseline (82.7 %) to Year 2 (90.6 %), OR= 1.65, p-value< 0.05. Similarly, the mean interval from screening to colposcopy decreased significantly from baseline (79 days) to Year 2 (49 days), to Years 3 and 4 (40 and 41 days, respectively), p < 0.001. Our results suggest that multicomponent interventions can improve and sustain appropriate and timely colposcopy among women in medically underserved regions, improving cervical cancer prevention efforts in resource-limited settings.

Interventions to increase follow-up of abnormal cervical cancer screening results: A systematic literature review and meta-analysis

Introduction Ensuring timely follow-up of abnormal screening results is essential for eliminating cervical cancer. Objective The purpose of the study was to review single and multicomponent interventions designed to improve follow-up of women with abnormal cervical cancer screening results. We report on effectiveness across studies, and describe what aspects of these interventions might be more impactful. Methods Publications were searched between January 2000 and December 2022. The search included observational, quasi-experimental (pre-post studies) and randomized controlled studies describing at least one intervention to increase follow-up of women with abnormal cervical cancer screening results. Outcomes of studies included completion of any follow-up (i.e., attending a follow-up appointment), timely diagnosis (i.e., colposcopy results within 90 days of screening) and time to diagnostic resolution (i.e., days between screening and final diagnosis). We assessed risk of bias for observational and quasi-experimental studies using the Newcastle-Ottawa Scale (NOS) tool and the Cochrane collaboration tool for randomized studies. We conducted a meta-analysis using studies where data were provided to estimate a summary average effect of the interventions on follow-up of patients and to identify characteristics of studies associated with an increased effectiveness of interventions. We extracted the comparison and intervention proportions of women with follow-up before and after the intervention (control and intervention) and plotted the odds ratios (ORs) of completing follow-up along with the 95% confidence intervals (CIs) using forest plots for the interventions vs. controls when data were available. Findings From 7,457 identified studies, 28 met the inclusion criteria. Eleven (39%) of the included studies had used a randomized design. Most studies (63%) assessed completion of any follow-up visit as the primary outcome, whereas others measured time to definite diagnosis (15%) or diagnostic resolution (22%). Navigation was used as a type of intervention in 63% of the included studies. Most interventions utilized behavioral approaches to improve outcomes. The overall estimate of the OR for completion of follow-up for all interventions was 1.81 (1.36–2.42). The highest impact was for programs using more than one approach (multicomponent interventions) to improve outcomes with OR = 3.01 (2.03–4.46), compared with studies with single intervention approaches with OR = 1.56 (1.14–2.14). No statistical risks were noted from publication bias or small-study effects in the studies reviewed. Conclusion Our findings revealed large heterogeneity in how follow-up of abnormal cervical cancer screening results was defined. Our results suggest that multicomponent interventions were more effective than single component interventions and should be used to improve follow-up after abnormal cervical cancer screening results. Navigation appears to be an important tool for improving follow-up. We also provide recommendations for future studies and implications for policy in terms of better defining outcomes for these interventions.

The Capulana study: a prospective evaluation of cervical cancer screening using human papillomavirus testing in Mozambique

Cervical cancer is the leading cause of cancer and related deaths among women in Mozambique. There is limited access to screening and few trained personnel to manage women with abnormal results. Our objective was to implement cervical cancer screening with human papillomavirus (HPV) testing, with navigation of women with abnormal results to appropriate diagnostic and treatment services. We prospectively enrolled women aged 30-49 years living in Maputo, Mozambique, from April 2018 to September 2019. All participants underwent a pelvic examination by a nurse, and a cervical sample was collected and tested for HPV using the careHPV test (Qiagen, Gaithersburg, Maryland, USA). HPV positive women were referred for cryotherapy or, if ineligible for cryotherapy, a loop electrosurgical excision procedure. Women with findings concerning for cancer were referred to the gynecologic oncology service. Participants (n=898) had a median age of 38 years and 20.3% were women living with the human immunodeficiency virus. HPV positivity was 23.7% (95% confidence interval 21.0% to 26.6%); women living with human immunodeficiency virus were twice as likely to test positive for HPV as human immunodeficiency virus negative women (39.2% vs 19.9%, p<0.001). Most HPV positive women (194 of 213, 91.1%) completed all steps of their diagnostic work-up and treatment. Treatment included cryotherapy (n=158, 77.5%), loop electrosurgical excision procedure (n=30, 14.7%), or referral to a gynecologist or gynecologic oncologist (n=5, 2.5%). Of eight invasive cervical cancers, 5 (2.8%) were diagnosed in women living with human immunodeficiency virus and 3 (0.4%) in human immunodeficiency virus negative women (p=0.01). Cervical cancer screening with HPV testing, including appropriate follow-up and treatment, was feasible in our study cohort in Mozambique. Women living with human immunodeficiency virus appear to be at a significantly higher risk for HPV infection and the development of invasive cervical cancer than human immunodeficiency virus negative women.

Addressing high cervical cancer rates in the Rio Grande Valley along the Texas–Mexico border: a community-based initiative focused on education, patient navigation, and medical provider training/telementoring

Aims: Cervical cancer incidence and mortality rates are approximately 55% higher in the Rio Grande Valley (RGV) along the Texas–Mexico border compared with the average rates in the US. Our aim was to improve cervical cancer prevention efforts in the RGV through a comprehensive multilevel intervention initiative focused on community education, patient navigation, and training of local providers. Methods: We initiated a program in the RGV which consisted of (1) community education, (2) patient navigation, and (3) a training/mentoring program for local medical providers including hands-on training courses coupled with telementoring using Project ECHO® (Extension for Community Health Outcomes). We assessed the number of women undergoing cervical cancer screening, diagnosis, and treatment at three participating clinics caring for underserved women in the region. Results: From November 2014 to October 2018, 14,846 women underwent cervical cancer screening. A total of 2030 (13.7%) women underwent colposcopy for abnormal results (179% increase over baseline) and 453 women underwent loop electrosurgical excision procedures (LEEPs) for treatment of cervical dysplasia. Invasive cancer was diagnosed in 39 women who were navigated to a gynecologic oncologist for treatment. Seven local medical providers were trained to perform colposcopy and/or LEEP. Project ECHO telementoring videoconferences were held every 2 weeks for a total 101 sessions with an average of 22 participants per session and a total of 180 patient cases presented and discussed. Conclusions: Our program led to a large number of women undergoing diagnosis and treatment of cervical dysplasia in the RGV. If sustained, we anticipate these efforts will decrease cervical cancer rates in the region. The program is currently being expanded to additional underserved areas of Texas and globally to low- and middle-income countries.

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.

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

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. 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. 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. 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.

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.

Long-term impact of cervical ablation in visual assessment of the squamocolumnar junction: implications for subsequent screening and follow-up

Cervical cancer screen-and-treat programs, which combine human papillomavirus (HPV)-based screening with immediate ablation of lesions, are a key strategy for reducing cervical cancer burden in low-resource settings. Although ablation is known to impair squamocolumnar junction (SCJ) visibility in the short-term, its long-term effects remain unclear, with potential implications for subsequent screening and follow-up. This study evaluated whether prior ablation is associated with incomplete SCJ visualization approximately 5 years post-treatment. We analyzed data from the Cervical Cancer Prevention in El Salvador program. Women aged 34 to 55 years who previously participated in Cervical Cancer Prevention in El Salvador were invited for HPV testing approximately 5 years after their initial screening. Those with positive results were further evaluated through visual inspection with acetic acid and colposcopy. We used generalized linear models to assess the association between prior ablation and incomplete SCJ visualization, adjusting for age, parity, and time since the initial HPV screen. Incomplete SCJ visualization was more frequent among women with prior ablation compared to those without previous treatment, both during colposcopy (47% vs 28%; OR 2.34, 95% CI 1.20 to 4.56) and visual inspection with acid (40% vs 25%; OR 2.06, 95% CI 1.05 to 4.01). Older age was also associated with impaired visualization, but the association between prior ablation and incomplete SCJ visibility remained significant after adjustment. Ablative treatment has a sustained impact on SCJ visualization that persists for years after the procedure, limiting the effectiveness of visualization-based surveillance. These findings underscore the need for efficient and affordable triage strategies to minimize unnecessary ablation in screen-and-treat programs and improve long-term follow-up care in low-resource settings.

A randomized clinical trial to assess the effectiveness of thermal ablation versus loop electrosurgical excision procedure for cervical cancer risk reduction in women living with HIV in Mozambique.

Cervical cancer remains a leading cause of death in low- and middle-income countries. Women living with human immunodeficiency virus (HIV) carry a 6-fold higher risk of cervical cancer than the general population. The effectiveness of thermal ablation versus loop electrosurgical excision procedure (LEEP) in women living with HIV is uncertain, prompting this study. To compare the effectiveness of thermal ablation versus LEEP for the management of abnormal cervical cancer screening results in women living with HIV. Thermal ablation is non-inferior to LEEP for treatment of cervical intra-epithelial neoplasia (CIN) 2/3 and high-risk human papillomavirus (hrHPV) infection in women living with HIV. This is a prospective randomized clinical trial. Participants undergo screening with primary hrHPV testing. Those with positive hrHPV results undergo visual inspection with acetic acid and a review of genotyping results to determine eligibility for treatment. Those who are hrHPV-positive and positive by visual assessment with acetic acid, or human papillomavirus16/18 positive regardless of visual assessment with acetic acid result, are randomized to thermal ablation or LEEP. Participants undergo follow-up at 4 to 8 weeks, 6 months, and 12 months post-procedure. Participants include 25 to 49-year-old women living with HIV in Mozambique. Exclusion criteria include pregnancy, previous total hysterectomy, history of cervical cancer or prior treatment for CIN, or any condition that would preclude adherence to the study protocol. Persistent or recurrent CIN 2/3 (or worse diagnosis) and hrHPV infection at 12 months after initial treatment. To meet our primary objectives and to achieve a power of 0.8 (α = 0.025), we will need to randomize 126 participants with CIN 2/3, 63 to thermal ablation, and 63 to LEEP. We estimate that this will require screening a total of 4844 women living with HIV. We anticipate that study accrual will be completed in 3 years (2027), with an additional 18 months to complete all follow-up visits and data analysis. We anticipate presenting results in 2029. ClinicalTrials.gov #NCT06326294.

Efficacy of topical treatments for high-risk human papillomavirus in preventing CIN II+ lesions: a systematic review

This study aimed to systematically review the literature regarding topical therapies for reducing the risk of cervical intra-epithelial neoplasia (CIN) grade 2 or higher (CIN II+) lesions among women with high-risk human papillomavirus (HPV) infection and histologically confirmed CIN I or either no cervical lesions. We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered the protocol in PROSPERO (CRD42024629608). We searched Ovid MEDLINE, Ovid EMBASE, Cochrane Central, and ClinicalTrials.gov from inception through December 16, 2024 for randomized controlled trials evaluating any cervical topical treatment in women with high-risk HPV and, at most, CIN I. The primary outcome was progression to histologically confirmed CIN II+. Secondary outcomes were treatment-related adverse events. Of 305 records, 19 full-text articles were reviewed. Finally, 16 trials were assessed. None met all our eligibility criteria, with some trials being excluded for multiple reasons. Twelve were excluded due to an inadequate study population (included women with CIN II+, lacked histologic confirmation of lesion grade, or lacked confirmatory high-risk HPV testing), 4 used inappropriate interventions, and 2 did not include a placebo or watchful waiting comparator. Although many studies reported HPV clearance or cytologic regression, none were powered or designed to assess progression to CIN II+. The current evidence from randomized trials is insufficient to determine whether topical cervical therapies reduce the risk of progression to CIN II+ in women with high-risk HPV infection. Future trials should prioritize histologic outcomes and adhere to current management protocols to establish the clinical utility of such therapies.