Carla Carrilho

Cervical Cancer Outcomes in Mozambique: Impact of an International Gynecologic Oncology Training Program

PURPOSE Cervical cancer is the most common cancer among women in Mozambique and is a major health burden. Surgery for cervical cancer is currently performed at only one hospital in the country, Maputo Central Hospital. Before 2020, there were no gynecologists in Mozambique trained to care for women with cervical cancer. In 2017, the International Gynecologic Cancer Society (IGCS) started a gynecologic oncology training program in Mozambique, and in 2020, the first three fellows graduated from this program. The main objective of this study was to report the outcomes of patients with cervical cancer who were treated surgically by the three newly trained Mozambican gynecologic oncologists. METHODS We performed a retrospective chart review of women diagnosed with cervical cancer who underwent surgical treatment by the Mozambican gynecologic oncologists between November 2020 and October 2022. The outcome of interest was survival at 2 years. RESULTS Thirty-three patients underwent radical hysterectomy with pelvic lymphadenectomy for cervical cancer treatment. The median age at diagnosis was 43 years. After surgery, 15 patients (45%) were dispositioned to surveillance and 18 (55%) were referred for adjuvant treatment with radiotherapy and/or chemotherapy. All patients had follow-up data available, with a median follow-up time of 19 months (range, 0.2 to 37.5). Only one patient died, and the overall survival is 95.7% (95% CI, 87.7% to 100%) at 12.7 months. CONCLUSION The IGCS program has provided training to physicians at Maputo Central Hospital, resulting in surgery for cervical cancer being available to patients in Mozambique. This is an important step in the global elimination of cervical cancer.

Differential etiopathogenic features of vulvar squamous cell carcinomas in sub‐Saharan Africa and Europe

AbstractTwo pathways have been described for vulvar squamous cell carcinomas (VSCC), one associated with human papillomavirus (HPV), and the other HPV‐independent. We compared the etiopathogenic features of a series of VSCC from Mozambique, a sub‐Saharan country with high prevalence of HPV and HIV, with those of Spain, a European country with low prevalence of HPV and HIV. All VSCC diagnosed at the two institutions from January 2018 to December 2020 were included (n = 35 and n = 41, respectively). HPV DNA detection and genotyping, and immunohistochemistry for p16 and p53 were performed. Tumors showing p16 positive staining and/or HPV DNA positivity were considered HPV‐associated. 34/35 tumors (97%) from Mozambique and 8/41 (19%) from Spain were HPV‐associated (P < .001). Mean age of the patients from Mozambique and Spain was 45 ± 12 and 72 ± 14, respectively (P < .001). No differences were found in terms of HPV genotypes or multiple HPV infection rates. 1/35 tumors (3%) from Mozambique and 29/41 (70%) from Spain showed abnormal p53 immunostaining (P < .001). In contrast with the predominance of HPV‐independent VSCC affecting old women in Europe, most VSCC in sub‐Saharan Africa are HPV‐associated and arise in young women. This data may have important consequences for primary prevention of VSCC worldwide.

Cervical cancer in Mozambique: Clinical characteristics, treatment and survival of incident cases admitted to the Oncology Service of Maputo Central Hospital in 2016‐2018

AbstractIn Mozambique, cervical cancer is the most frequent cancer in women. However, studies about cervical cancer treatment and prognosis are scarce. We describe the clinical characteristics, treatment and survival of patients with cervical cancer admitted to Maputo Central Hospital (MCH) in 2016 to 2018. Sociodemographic, clinical and cancer‐related data were retrieved from clinical records of patients admitted to the Oncology Service of the MCH with an incident cervical cancer in 2016 to 2018 (n = 407). The Pathology Service database was used to obtain information regarding pathological diagnosis. Survival data was obtained through the MCH Cancer Registry and clinical records. Odds ratios for the association between patients' characteristics and the diagnosis of advanced stage cancer were computed using logistic regression. Survival analyses were performed using the Kaplan‐Meier estimator. A total of 91.2% of the patients were diagnosed with advanced disease (stage IIB‐IV) and squamous cell carcinoma was the predominant histological subtype. Most of the patients underwent chemotherapy (93.1%) but <7% were submitted to surgery, radiotherapy or brachytherapy. Those living with HIV had 3.4‐fold higher odds of advanced disease. Overall survival was 72.7% (95% confidence interval [CI]: 67.9‐77.0) at 1‐year and 51.0% (95%CI: 45.3‐56.3) at 2‐years. Those with early stage (IA‐IIA) and asymptomatic at diagnosis had a significantly higher 2‐year overall survival. In Mozambique, cervical cancer is diagnosed mostly in advanced stages, resulting in poor prognosis. This highlights the importance of HPV vaccination and screening, to decrease the burden of cervical cancer in this context.

Expanding Cervical Cancer Screening in Mozambique: Challenges Associated With Diagnosing and Treating Cervical Cancer

PURPOSE Mozambique has one of the highest burdens of cervical cancer globally. Treatment options are few as most women present with advanced disease, and there are limited trained health professionals and health care resources. The objective of this study was to describe the outcomes of women diagnosed with invasive cancer as part of the Mozambican women undergoing cervical cancer screening with human papillomavirus (HPV) testing in conjunction with family planning services (MULHER) study. MATERIALS AND METHODS Women age 30-49 years were prospectively enrolled in the MULHER study and offered screening with primary HPV testing followed by treatment of screen-positive women with thermal ablation or excision as appropriate. Women with cervical examination findings suspicious for cancer were referred to one of the three gynecologic oncologists in the country. RESULTS Between January 2020 and January 2023, 9,014 women underwent cervical cancer screening and 30 women were diagnosed with cervical cancer. In this cohort, four patients (13.3%) had early-stage disease, 18 (60.0%) had locally advanced disease, one (3.3%) had distant metastatic disease, and seven (23.3%) did not have staging information available. Five patients (16.6%) died without receiving oncologic treatment, and seven patients (23.3%) are still awaiting treatment. Of the remaining 18 patients, three (17.6%) underwent surgery and four (23.5%) received radiotherapy. Eleven (36.7%) patients received only chemotherapy. CONCLUSION As cervical screening programs are implemented in low-resource settings, there will likely be an increase in the number of women diagnosed with invasive cervical cancer. Our results in Mozambique demonstrate the need to increase access to advanced surgery, radiation, and palliative care services.

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.

Scaling cervical cancer screening in Mozambique: analysis of loop electrosurgical excision procedure (LEEP) specimens

As cervical cancer screening programs are implemented and expanded, an increasing number of women require loop electrosurgical excision procedure (LEEP) for treatment of pre-invasive cervical disease. Our objective was to describe the pathological results of LEEP specimens performed as part of the MULHER study and identify factors associated with positive LEEP margins. The MULHER study enrolled 9014 women who underwent HPV testing followed by visual assessment for treatment (VAT) using visual inspection with acetic acid (VIA) and thermal ablation for those with positive results. Participants with lesions ineligible for ablation underwent LEEP. Pathology reports were reviewed for specimen size/volume, number of fragments, pathological diagnosis and margin status. Multivariable regression analysis was performed to identify variables associated with positive LEEP margins. 169 participants underwent LEEP. The median age was 38 years (range 30-49). 65.1% were women living with HIV. Pathological diagnosis was available for 154 patients and included cancer (n=6, 3.9%); cervical intraepithelial neoplasia (CIN) 2/3 (n=75, 48.7%); CIN 1 (n=67, 43.5%); and normal/benign findings (n=6,3.9%). 31.8% of LEEP specimens were removed in more than one fragment. The mean specimen volume was 2.9 cm Our results showed a high number of LEEP specimens with positive margins. Additional evaluation is needed to better understand the characteristics of precancerous cervical lesions in this high-risk population. As cervical cancer screening programs are scaled in Mozambique and other lower-resource countries, there is a need to train providers to perform high-quality LEEP and for accurate and timely pathological interpretation.