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

Abstract

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.

INTRODUCTION

Cervical cancer is the fourth most common cancer in women globally with an estimated 661,021 new cases and 348,189 deaths in 2022,¹ with the highest rates of cervical cancer incidence and mortality in low- and middle-income countries. In Mozambique, a country in sub-Saharan Africa with a population of approximately 32 million, cervical cancer is the most frequent malignant neoplasm among women, with 5,325 new cases and 3,850 deaths annually.²

CONTEXT

• Key Objective

• What are the impacts and outcomes of an international training program in gynecologic oncology in Mozambique?

• Knowledge Generated

• We demonstrated that an international training program in gynecologic oncology is a feasible approach to develop clinical capacity to care for women with cervical cancers in Mozambique. This program has made cervical cancer surgery available and accessible in a country with no formal, in-country training program, enhancing care for patients with cervical cancer.

• Relevance

• Strengthening and expanding this program will increase access to care for gynecological cancer patients across Mozambique, significantly contributing to the path of the elimination of cervical cancer.

The International Gynecologic Cancer Society (IGCS) started the Global Gynecologic Oncology Fellowship Program in 2017. This fellowship training program is designed to strengthen gynecologic cancer care in regions of the world where there is no formal training in gynecologic oncology. Mozambique was one of the five pilot training sites at the initiation of this program. The IGCS currently runs 22 similar programs in 18 countries.³

The IGCS fellowship is a 2-year education and training program that occurs in-country with the support of international mentors.⁴ The international mentors travel to the country 2-4 times per year to provide hands-on surgical training. This is supplemented with regular virtual meetings including monthly tumor boards using Project ECHO (Extension for Community Healthcare Outcomes).⁵ The fellows also spend 1 to 3 months at the international mentor's institution. Before the IGCS training program, there were no gynecologists in Mozambique trained to perform surgeries and care for women with gynecologic cancers. The first three physicians graduated from this program in 2020.^3,4

The objective of this study was to describe oncologic treatment outcomes and overall survival for the first cohort of women diagnosed with cervical cancer and treated with surgery in Mozambique by these IGCS graduates.

METHODS

This is a retrospective, observational, hospital-based study of the first cohort of women who underwent surgical treatment for cervical cancer in Mozambique by Mozambican gynecologic oncologists who completed the IGCS fellowship.

The study was carried out at Maputo Central Hospital, a public hospital, in the Department of Gynecology and Obstetrics. Maputo Central Hospital is a general quaternary level care hospital, located in the capital of the country. The study was approved by the Institutional Committee for Bioethics in Health of the Faculty of Medicine/Maputo Central Hospital (CIBS FM&HCM/002/2023). Informed consent was not required given the retrospective nature of this study.

IGCS Global Gynecologic Oncology Fellowship Program Structure in Mozambique

The IGCS Global Fellowship Program is a comprehensive 2-year educational program designed for countries that do not have formal training in gynecologic oncology. This program started in 2017 with five pilot sites, including Mozambique.⁶ The team of international mentors in Mozambique are from Brazil, because of the common language, and from MD Anderson because of collaboration with the Mozambique Ministry of Health.

In 2017, with the initiation of the IGCS training program, a formal structure to the mentors' visits and training videoconferences was introduced.⁵ Three fellows were accepted into the program. Surgery was performed by the Mozambican fellows with the support and supervision of the Brazilian mentors during regular visits. The fellows took their final examination and graduated from the fellowship in 2020. After graduation, the Mozambican gynecologic oncologists began performing radical hysterectomies and other surgeries for gynecologic cancers independently.

Surgical Patients

Patients were identified retrospectively from the fellows' surgery logs that were kept as part of the IGCS Global Gynecologic Oncology Fellowship program and continued after graduation as well as from operating room surgical logs. Patients were included if they had a diagnosis of cervical cancer and had undergone surgery at Maputo Central Hospital performed by one or more of the three Mozambican gynecologic oncologists.

Data abstracted from the medical records included sociodemographic information, 2018 International Federation of Gynecology and Obstetrics (FIGO) stage,³ HIV status, pathology results, surgical details, adjuvant treatment (chemotherapy and/or radiotherapy), and survival.

Of note, most patients with cervical cancer undergo imaging with computed tomography (CT) scan before surgery. Magnetic resonance imaging and positron emission tomography scans are not available at Maputo Central Hospital. The 2018 FIGO stage was determined before surgery on the basis of pelvic examination, as well as CT scan and biopsy results if available. If necessary, the stage was corrected postoperatively on the basis of intraoperative findings and final pathology results. Furthermore, in Mozambique, the availability of radiotherapy is limited with only one linear accelerator available for the entire country. Radical hysterectomy is therefore performed in patients with up to stage IIA2 disease. Neoadjuvant chemotherapy is also sometimes used.

Descriptive statistics were used to summarize the demographic and clinical characteristics of patients. Study data were collected and managed using Research Electronic Data Capture tools hosted at MD Anderson.⁷ The Clopper-Pearson method was used to estimate 95% CIs for percentages.⁸ The Goodman method was used to estimate 95% CIs for the percentage of downstaging, agreement, and upstaging between clinical stage and pathological stage.⁹ The product limit estimator of Kaplan-Meier¹⁰ was used to estimate overall survival. All statistical analyses were performed using SAS 9.4 for Windows (Copyright 2002-2012 by SAS Institute Inc, Cary, NC) and StatXact-7 for Windows (Copyright 2005, 1989-2005, Cytel Software Corporation, Cambridge, MA). Figures were created using R and RStudio.¹¹

RESULTS

From November 2020 to October 2022, 33 patients were identified who underwent surgery for cervical cancer. The demographic and clinical characteristics of patients are summarized in Table 1. The median age of patients was 43 years (range, 29-73 years). Two thirds of the patients were women living with HIV (WLWH). FIGO 2018 stage before surgery ranged from IB1 to IIA2, with eight patients (24%) diagnosed with stage IIA1/IIA2 disease. One patient received neoadjuvant chemotherapy.

TABLE 1.

Demographic and Clinical Characteristics

Characteristic	Total (N = 33)
Age, years
No.	32
Mean (SD)	44 (9.5)
Median (range)	43 (29-73)
HIV status, No. (%)
Positive	22 (67)
Negative	9 (27)
Unknown	2 (6)
Preoperative clinical stage, No. (%)
IB1	4 (12)
IB2	11 (33)
IB3	10 (30)
IIA1	7 (21)
IIA2	1 (3)
Biopsy results available, No. (%)
Yes	27 (82)
No	6 (18)
Biopsy result, No. (%)
Adenocarcinoma	4 (15)
Squamous cell carcinoma	23 (85)
Days from biopsy-to-biopsy result
No.	26
Mean (SD)	25.8 (13.3)
Median (range)	24 (6-62)
Days from biopsy result to surgery
No.	26
Mean (SD)	215.3 (152.9)
Median (range)	159 (38-701)
Days from surgery to surgical pathology result
No.	30
Mean (SD)	39.7 (38.6)
Median (range)	33 (17-234)
Type of surgery, No. (%)
Radical hysterectomy with bilateral pelvic lymphadenectomy	33 (100)
Surgical pathology report available, No. (%)
Yes	30 (91)
No	3 (9)
Surgical pathology result, No. (%)
Adenocarcinoma	6 (20)
Squamous cell carcinoma	18 (60)
CIN 2	1 (3)
CIN 3	5 (17)
Postoperative stage, No. (%)
IA1	2 (7)
IA2	2 (7)
IB1	2 (7)
IB2	6 (20)
IB3	4 (13)
IIA1	1 (3)
IIA2	2 (7)
IIIC	4 (13)
IVA	1 (3)
No cancer (CIN 2/3)	6 (20)
Adjuvant therapy, No. (%)
None	17 (52)
Chemotherapy	2 (6)
Radiotherapy	1 (3)
Chemotherapy and radiotherapy	11 (33)
Unknown	2 (6)
Type of follow-up, No. (%)
Referral to clinical oncology	18 (55)
Surveillance	15 (45)
Vital status at last follow-up, No. (%)
Alive without disease	26 (79)
Alive with disease	3 (9)
Died	1 (3)
Lost to follow-up	3 (9)
Follow-up time, months
No.	33
Mean (SD)	18.0 (11.7)
Median (range)	19 (0.2-37.5)
Follow-up time for patients with cancer, months
No.	24
Mean (SD)	19.8 (9.7)
Median (range)	20.5 (1.5-37.5)

Abbreviations: CIN, cervical intraepithelial neoplasia; SD, standard deviation.

All patients had a cervical biopsy confirming cancer before surgery. However, the data were only available for 27 patients. For these 27 patients, the median time from biopsy-to-biopsy result was 24 days (range, 6-62 days). From the biopsy results, 23 patients (85%) were diagnosed with squamous cell carcinoma, and four (15%) were diagnosed with adenocarcinoma. The time from biopsy-to-biopsy result for each patient is shown in Figure 1.

FIG 1.

Days from biopsy-to-biopsy result.

All patients underwent open radical hysterectomy with bilateral pelvic lymphadenectomy. The median time from biopsy result to surgery was 159 days (range, 38-701 days). The patients were referred to Maputo Central Hospital from different provinces of Mozambique, as this is the only hospital where surgical treatment for cervical cancer is available, delaying the treatment in some cases. The time from biopsy result to surgery for each patient is shown in Figure 2. Seventeen patients (17/33, 52%) had no adjuvant therapy, whereas 11 (11/33, 33%) had adjuvant radiotherapy with weekly cisplatin (chemoradiation), two (2/33, 6%) had chemotherapy alone, one (1/33, 3%) had radiotherapy alone, and information was not available for two patients (2/33, 6%).

FIG 2.

Days from biopsy result to surgery.

Thirty patients had surgical pathology results available. The median time from surgery to pathology result was 33 days (range, 17-234 days; Fig 3). Eighteen patients (18/30, 60%) had squamous cell carcinoma, six (6/30, 20%) had adenocarcinoma, and six (6/30, 20%) had cervical intraepithelial neoplasia (CIN) 2/3. Final pathology results were not available for three patients.

FIG 3.

Days from surgery to surgical pathology result.

Of the 26 patients with both a biopsy result and a surgical pathology result available, the histologic findings were consistent in 19 patients (73% [95% CI, 52% to 88%]; Table 2). For the seven patients where they differed: two patients had squamous cell carcinoma on their biopsy but adenocarcinoma on their hysterectomy specimen and five patients had squamous cell carcinoma on their biopsy but were found to have only CIN 2/3 on their hysterectomy specimen.

TABLE 2.

Agreement Between Biopsy and Surgical Pathology

Biopsy Result	Surgical Pathology Result, No. (%)				Total
	Adenocarcinoma	SCC	CIN 2	CIN 3
Adenocarcinoma	4 (15)	0	0	0	4 (15)
SCC	2 (8)	15 (58)	1 (4)	4 (15)	22 (85)
Total	6 (23)	15 (58)	1 (4)	4 (15)	26 (100)

Abbreviations: CIN, cervical intraepithelial neoplasia; SCC, squamous cell carcinoma.

Thirty patients had both preoperative clinical stage and final pathology results available. The stage was consistent in seven patients (23% [95% CI, 10% to 45%]). For the remaining 23 patients, the stage was corrected based on intraoperative findings and final pathology results. Fifteen patients (50% [95% 30% to 70%]) were found to have lower-stage disease, and eight patients (27% [95% CI, 12% to 49%]) were found to have higher-stage disease (Table 3).

TABLE 3.

Agreement Between Preoperative Clinical Stage and Postoperative Stage on the Basis of Intraoperative Findings and Final Pathology Results

Clinical Stage	Postoperative Stage, No. (%)										Total
	No Cancer	IA1	IA2	IB1	IB2	IB3	IIA1	IIA2	IIIC	IVA
No cancer	0	0	0	0	0	0	0	0	0	0	0 (0)
IA1	0	0	0	0	0	0	0	0	0	0	0 (0)
IA2	0	0	0	0	0	0	0	0	0	0	0 (0)
IB1	2 (7)	0	0	1 (3)	1 (3)	0	0	0	0	0	4 (13)
IB2	1 (3)	2 (7)	2 (7)	1 (3)	2 (7)	1 (3)	0	0	0	0	9 (30)
IB3	2 (7)	0	0	0	1 (3)	2 (7)	0	0	3 (10)	1 (3)	9 (30)
IIA1	1 (3)	0	0	0	2 (7)	1 (3)	1 (3)	1 (3)	1 (3)	0	7 (23)
IIA2	0	0	0	0	0	0	0	1 (3)	0	0	1 (3)
IIIC	0	0	0	0	0	0	0	0	0	0	0 (0)
IVA	0	0	0	0	0	0	0	0	0	0	0 (0)
Total	6 (20)	2 (7)	2 (7)	2 (7)	6 (20)	4 (13)	1 (3)	2 (7)	4 (13)	1 (3)	30 (100)

All 33 patients had follow-up data available. The median follow-up time was 19 months (range, 0.2-37.5). Twenty-three (70%) of the 33 patients had at least 12 months of follow-up. There was only one patient death, and this occurred 12.7 months after surgery and was due to disease relapse.

The overall survival was 95.7% (95% CI, 87.7% to 100%) at 12.7 months. The median overall survival was not reached. The Kaplan-Meier curve of overall survival for all patients is shown in Figure 4.

FIG 4.

Overall survival. OS, overall survival.

The median follow-up for the 24 patients who had invasive cancer on final surgical pathology was 20.5 months (range, 1.5-37.5). Twenty (83%) of these 24 patients had at least 12 months of follow-up. Survival for the patients with invasive cancer was 95% at 12.7 months (95% CI, 85.9% to 100%). The median survival for this group was not reached. The Kaplan-Meier curve of survival for patients with invasive cancer is shown in Figure 5.

FIG 5.

Overall survival (patients with cancer). OS, overall survival.

DISCUSSION

The primary findings from our study are that 33 women with presumed early-stage cervical cancer underwent radical hysterectomy with pelvic lymphadenectomy. This was the first cohort of patients treated by the first Mozambican gynecologic oncologists who were trained through the IGCS Global Gynecologic Oncology Fellowship Program. The overall survival was 95.7% at 12.7 months with only one patient who died of disease. The availability of surgical treatment for early-stage disease is a great improvement in the care of women with cervical cancer in Mozambique.

In our study, a high proportion of the women (67%) were living with HIV. It is well established that HIV is a significant risk factor with a 6-fold increase in cervical cancer among WLWH.^12,13 Our team conducted a previous study (MULHER Study) in Mozambique. Of 9,014 patients received human papillomavirus (HPV) screening, 2805 were HPV-positive patients and 2,588 (92.3%) returned for all steps of their diagnostic workup and treatment. Of the 31 patients who were diagnosed with invasive cancer, 62.5% were living with HIV.¹⁴ The prevalence of HIV in Mozambique is approximately 15% among adult Mozambican women contributing to the high cervical cancer rates.¹⁵

We noted significant discrepancies in the pathology results between the cervical biopsy and the radical hysterectomy specimen in several patients. A previous study by Stuebs et al conducted in Germany compared the results of colposcopic biopsy and surgical specimen and reported an accuracy of 71.9% for benign lesions, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and cervical cancer. They noted that 11.8% of the patients had more advanced lesions, and 16.2% had less advanced lesions than the biopsy result.¹⁶ In Mozambique, there are only 14 pathologists and four Anatomical Pathology Departments throughout the country of 32 million people.¹⁷ There are very few pathologists with advanced training in gynecologic cancers and limited experience as cervical screening and cervical biopsies are just being scaled up. Furthermore, several patients had their stage corrected because of intraoperative findings that were not known because of a lack of imaging and/or incorrect interpretation. Multidisciplinary care has been introduced in Mozambique for cancer care,¹⁷ and there is a new initiative that is being introduced to strengthen this model. This will consist of formalizing multidisciplinary care including additional training for oncology providers (surgeons, medical, and radiation oncologists) as well as pathologists and radiologists working in oncology.

In our study, significant delays were noted from presentation to surgery. In Mozambique, approximately 6.18 million women are at risk of developing cervical cancer.¹⁶ Maputo Central Hospital is the only institution in the country with the personnel and resources to perform radical hysterectomy. In this study, we found a median of 24 days from the time of biopsy-to-biopsy result and 159 days from result to surgery. The three IGCS graduates are now training the next class of gynecologic oncology fellows and hope to build further capacity for cervical cancer surgery in Maputo and in other regions of the country.

A high number of women in our study required adjuvant treatment. This is in part due to the higher stage of many of the patients. Mozambique has limited radiotherapy services with only one linear accelerator for the entire country, and brachytherapy is not currently available.¹⁸

Despite these challenges, the newly graduated IGCS gynecologic oncologists were able to provide surgical treatment to 33 women with cervical cancer. The overall survival was 95.7% at 12.7 months. Glasmeyer et al conducted a study in Tanzania of 231 patients with cervical cancer of different stages. For women diagnosed in early stages (FIGO I-IIA), the median survival time was 38.3 months, 16 months in advanced stage (FIGO IIB-IIIB), and 6.5 months late stage (FIGO IV) after diagnosis.¹⁹

Our study has several limitations. The follow-up time was short. There is no electronic medical record system in Mozambique and records may be misplaced or lost in the paper charting system resulting in limited data to include in this study. We were unable to provide important information such as CD4 count, complications, estimated blood loss, length of stay, and other variables. To address these limitations, there is a need to develop an electronic medical record system in Mozambique.

In conclusion, our study demonstrated the feasibility of a training model where gynecologic oncologists are trained in-country with the support of international mentors. The IGCS program is ongoing with continued support for the new graduates who are now training the next group of gynecologic oncologists. Parallel programs to strengthen multidisciplinary care including pathology and radiology will further support the management of women with cervical cancer. Future efforts are to strengthen and expand the training program at Maputo Central Hospital, so it can serve as an independent, national training site to train the next generation of gynecologic oncologists in Mozambique. Increasing the strength and depth of this program will increase access to care for gynecological cancer patients nationwide. The IGCS program training three gynecologic oncologists who have now performed 33 radical hysterectomies independently for the women in their community is an important step in the global elimination of cervical cancer.

AUTHOR CONTRIBUTIONS

Conception and design: Ricardina Rangeiro, Andre Lopes, Cesaltina Lorenzoni, Kathleen M. Schmeler, Mila P. Salcedo

Administrative support: Ricardina Rangeiro, Cesaltina Lorenzoni, Kathleen M. Schmeler, Mila P. Salcedo

Provision of study materials or patients: Ricardina Rangeiro, Dercia Changule, Siro Daud, Calisto Ferreira, Magda Ribeiro, Agostinho Daniel, Celso Bila, Cesaltina Lorenzoni

Collection and assembly of data: Ricardina Rangeiro, Andre Lopes, Dercia Changule, Cesaltina Lorenzoni, Kathleen M. Schmeler, Mila P. Salcedo

Data analysis and interpretation: Ricardina Rangeiro, Andre Lopes, Mark F. Munsell, Ellen Baker, Cesaltina Lorenzoni, Kathleen M. Schmeler, Mila P. Salcedo

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

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