Consensus on surgical technique for sentinel lymph node dissection in cervical cancer.

OBJECTIVE: The purpose of this study was to establish a consensus on the surgical technique for sentinel lymph node (SLN) dissection in cervical cancer. METHODS: A 26 question survey was emailed to international expert gynecological oncology surgeons. A two-step modified Delphi method was used to establish consensus. After a first round of online survey, the questions were amended and a second round, along with semistructured interviews was performed. Consensus was defined using a 70% cut-off for agreement. RESULTS: Twenty-five of 38 (65.8%) experts responded to the first and second rounds of the online survey. Agreement ≥70% was reached for 13 (50.0%) questions in the first round and for 15 (57.7%) in the final round. Consensus agreement identified 15 recommended, three optional, and five not recommended steps. Experts agreed on the following recommended procedures: use of indocyanine green as a tracer; superficial (with or without deep) injection at 3 and 9 o'clock; injection at the margins of uninvolved mucosa avoiding vaginal fornices; grasping the cervix with forceps only in part of the cervix is free of tumor; use of a minimally invasive approach for SLN biopsy in the case of simple trachelectomy/conization; identification of the ureter, obliterated umbilical artery, and external iliac vessels before SLN excision; commencing the dissection at the level of the uterine artery and continuing laterally; and completing dissection in one hemi-pelvis before proceeding to the contralateral side. Consensus was also reached in recommending against injection at 6 and 12 o'clock, and injection directly into the tumor in cases of the tumor completely replacing the cervix; against removal of nodes through port without protective maneuvers; absence of an ultrastaging protocol; and against modifying tracer concentration at the time of re-injection after mapping failure. CONCLUSION: Recommended, optional, and not recommended steps of SLN dissection in cervical cancer have been identified based on consensus among international experts. These represent a surgical guide that may be used by surgeons in clinical trials and for quality assurance in routine practice.

The evolution of a novel approach to building surgical capacity for cervical cancer in Africa.

The human, financial, and infrastructural resources required to effectively treat invasive cancer of the cervix are grossly inadequate in the African region, inclusive of a paucity of surgeons capable of performing life-saving radical pelvic surgery for early-stage disease, and the requisite medical ecosystem (blood banking, anesthesia, laboratory, imaging, diagnostics, etc.) Death without treatment, therefore, is a common sequela of cervical cancer in Africa. As African American gynaecologic oncology sub-specialists working in Africa and its Diaspora, we set out to find a way to alter these circumstances. Herein, we provide an overview of our efforts and how they evolved into a novel method of training that rapidly builds surgical capacity for the treatment of early-stage cervical cancer in resource-constrained environments.

Cancer research across Africa: a comparative bibliometric analysis.

INTRODUCTION: Research is a critical pillar in national cancer control planning. However, there is a dearth of evidence for countries to implement affordable strategies. The WHO and various Commissions have recommended developing stakeholder-based needs assessments based on objective data to generate evidence to inform national and regional prioritisation of cancer research needs and goals. METHODOLOGY: Bibliometric algorithms (macros) were developed and validated to assess cancer research outputs of all 54 African countries over a 12-year period (2009-2020). Subanalysis included collaboration patterns, site and domain-specific focus of research and understanding authorship dynamics by both position and sex. Detailed subanalysis was performed to understand multiple impact metrics and context relative outputs in comparison with the disease burden as well as the application of a funding thesaurus to determine funding resources. RESULTS: African countries in total published 23 679 cancer research papers over the 12-year period (2009-2020) with the fractional African contribution totalling 16 201 papers and the remaining 7478 from authors from out with the continent. The total number of papers increased rapidly with time, with an annual growth rate of 15%. The 49 sub-Saharan African (SSA) countries together published just 5281 papers, of which South Africa's contribution was 2206 (42% of the SSA total, 14% of all Africa) and Nigeria's contribution was 997 (19% of the SSA total, 4% of all Africa). Cancer research accounted for 7.9% of all African biomedical research outputs (African research in infectious diseases was 5.1 times than that of cancer research). Research outputs that are proportionally low relative to their burden across Africa are paediatric, cervical, oesophageal and prostate cancer. African research mirrored that of Western countries in terms of its focus on discovery science and pharmaceutical research. The percentages of female researchers in Africa were comparable with those elsewhere, but only in North African and some Anglophone countries. CONCLUSIONS: There is an imbalance in relevant local research generation on the continent and cancer control efforts. The recommendations articulated in our five-point plan arising from these data are broadly focused on structural changes, for example, overt inclusion of research into national cancer control planning and financial, for example, for countries to spend 10% of a notional 1% gross domestic expenditure on research and development on cancer.

Knowledge, Practice, and Attitudes of Physicians in Low- and Middle-Income Countries on Fertility and Pregnancy-Related Issues in Young Women With Breast Cancer.

PURPOSE: Fertility and pregnancy-related issues are highly relevant for young (≤ 40 years) patients with breast cancer. Limited evidence exists on knowledge, practice, and attitudes of physicians from low- and middle-income countries (LMICs) regarding these issues. METHODS: A 19-item questionnaire adapted from an international survey exploring issues about fertility preservation and pregnancy after breast cancer was sent by e-mail between November 2019 and January 2020 to physicians from LMICs involved in breast cancer care. Descriptive analyses were performed. RESULTS: A total of 288 physicians from Asia, Africa, America, and Europe completed the survey. Median age was 38 years. Responders were mainly medical oncologists (44.4%) working in an academic setting (46.9%). Among responders, 40.2% and 53.8% reported having never consulted the available international guidelines on fertility preservation and pregnancy after breast cancer, respectively. 25.0%, 19.1%, and 24.3% of responders answered to be not at all knowledgeable about embryo, oocyte, or ovarian tissue cryopreservation, respectively; 29.2%, 23.6%, and 31.3% declared that embryo, oocyte, and ovarian tissue cryopreservation were not available in their countries, respectively. 57.6% of responders disagreed or were neutral on the statement that controlled ovarian stimulation can be considered safe in patients with breast cancer. 49.7% and 58.6% of responders agreed or were neutral on the statement that pregnancy in breast cancer survivors may increase the risk of recurrence overall or only in those with hormone receptor-positive disease, respectively. CONCLUSION: This survey showed suboptimal knowledge, practice, and attitudes of physicians from LMICs on fertility preservation and pregnancy after treatment completion in young women with breast cancer. Increasing awareness and education on these aspects are needed to improve adherence to available guidelines and to promote patients' oncofertility counseling.

Establishing women's cancer care services in a fragile, conflict and violence affected ecosystem in Africa.

BACKGROUND: The majority of the world's poorest women (income < $1.90/day) reside in fragile, conflict and violence (FCV)-affected countries, like the Democratic Republic of the Congo. Health services in these settings have traditionally focused on immediate relief efforts, communicable diseases and malnutrition. Recent data suggests there is need to widen the focus to include cancer, as its incidence and mortality rates are rising. METHODS: Employing competency-based learning strategies, Congolese health professionals were trained to perform same-day cervical cancer screening and treatment of precancerous lesions of the cervix; same-day clinical breast examination and breast ultrasound diagnostics; surgical treatment of invasive cancers of the breast and cervix; and infusion of cytotoxic chemotherapy. Outpatient breast and cervical cancer care clinics, a chemotherapy suite and surgical theatres were outfitted with equipment and supplies. RESULTS: Combining local and regional hands-on training seminars with wise infrastructure investments, a team of US and Zambian oncology experts successfully implemented a clinical service platform for women's cancers in a private sector health facility in the Democratic Republic of the Congo. CONCLUSION: We forged a novel partnership between oncology health professionals from Africa and its Diaspora, international philanthropic organisations, a cancer medicine access initiative and an established African cancer centre to build women's cancer services in a FVC-affected African setting.

Building workforce capacity for the surgical management of cervical cancer in a fragile, low-income African nation-Democratic Republic of the Congo.

OBJECTIVES: Surgery is a cornerstone of the management of cervical cancer. Women diagnosed with cervical cancer in sub-Saharan Africa have very little access to specialised (gynaecologic oncology) surgical services. We describe our experiences and challenges of training local general gynaecologists to surgically treat early stage invasive cervical cancer at a private sector healthcare facility in a fragile, low-income African nation. METHODS: Implementation of the training curriculum began with assigned self-directed learning. It continued with on-site training which consisted of preoperative surgical video reviews, pre- and intra-operative assessment of disease status, deconstruction of the designated surgical procedure into its critical subcomponents and trainees orally communicating the steps of the surgical procedure with the master trainers. High-volume repetition of a single surgical procedure over a short time interval, intra-operative bedside mentoring, post-operative case review and mental narration were critical to the process of surgical skills transfer. RESULTS: Nineteen radical abdominal hysterectomies were successfully performed over four training visits; trainees were able to perform the procedure alone after eight cases; surgical complications decreased over time. The trainees have continued to perform the surgical procedures independently. CONCLUSION: Life-saving surgical capacity for the treatment of cervical cancer has been established and sustained at a private sector healthcare facility in a fragile, low-income African setting, through an innovative model of surgical training.

Leveraging a matrix of stakeholders to facilitate access to chemotherapy for women's cancers in the Democratic Republic of the Congo.

BACKGROUND: Cancer incidence is increasing worldwide. Over the next 20 years, the growing proportion of cases in low- and middle-income countries (LMICs) will account for an estimated 70% of all cancers diagnosed. The vast majority of cancer patients in LMICs will require chemotherapy, due to the advanced stage of their disease at the time of initial presentation. Unfortunately, the availability of cancer drugs in these environments is sparse, resulting in premature death and years of life lost. In an effort to lay a foundation for women's cancer control in the Democratic Republic of the Congo (DRC), we implemented a programme which combined workforce development, infrastructure creation and cancer drug access. This manuscript reports on our experience with the latter. METHODS: A private sector healthcare facility was selected as the programme implementation site. Workforce capacity was developed through a south-south partnership with an African national cancer centre. Cancer drugs were procured through a global cancer medicine access initiative. RESULTS: A new chemotherapy infusion unit was successfully established at the Biamba Marie Mutombo Hospital in Kinshasa, DRC. A team of Congolese healthcare providers was trained at the Cancer Disease Hospital in Zambia to safely and effectively administer chemotherapy for breast and cervical cancer. Over 100 breast and cervical cancer patients have been treated with 337 courses of chemotherapy, without any serious adverse events. CONCLUSION: Common barriers to cancer drug access and its administration can be eliminated using regional educational resources to build oncologic workforce capacity, private sector healthcare facilities for infrastructure support and pharmaceutical consortiums to procure low-cost cancer medicines. By leveraging a matrix of global, regional and local stakeholders, the prevailing status quo of very limited access to chemotherapy for women's cancers was creatively disrupted in DRC, Africa's largest fragile, conflict and violence-affected country.

Building a breast cancer detection and treatment platform in the Democratic Republic of the Congo by integrating training, service and infrastructure development.

BACKGROUND: Breast cancer is a leading cause of cancer-related morbidity and mortality in sub-Saharan Africa, a global region where opportunities for breast care of any type are extremely limited due to insufficient infrastructure, a paucity of clinical services and vast shortages of trained human resources. METHODS: A team of Zambian and US gynaecologic and breast oncology experts and nurse-specialists made multiple visits (each lasting 5 working days) to the Democratic Republic of the Congo (DRC), over a 2-year period. During each of five week-long site visits, hands-on training of local Congolese health providers was conducted during which time they were taught clinical breast exam (CBE), breast and axillary ultrasound, ultrasound-guided core needle biopsy/fine needle aspiration (FNA) and breast surgery. Simultaneous with the training exercises, a new breast care clinic was established and operationalised, and existing surgical theatres were upgraded. All activities were implemented in a private sector health care facility - Biamba Marie Mutombo Hospital - in the capital city of Kinshasa. RESULTS: From April 2017 to August 2020, a total of 5,211 women were identified as having breast abnormalities on CBE. Ages ranged from 26 to 86 years; median age: 42.0 (±14.1) years. Ultrasound abnormalities were noted in 1,420 (27%) clients, of which 516 (36%) met the criteria (indeterminate cystic lesion, solid or suspicious masses) for ultrasound-guided core needle biopsy or FNA. Pathology reports were available for 368 (71%) of the 516 clients who underwent biopsy, of which 164 were malignant and 204 benign. The majority (88%) of the cancers were advanced (TNM stages 3 and 4). Surgical procedures consisted of 183 lumpectomies, 58 modified radical mastectomies and 45 axillary lymph node dissections. Clinical competency for diagnostic and surgical procedures was reached early in the course of the training programme. CONCLUSION: By integrating onsite training with simultaneous investments in clinical service and infrastructure development, the barriers to breast cancer diagnosis and treatment were disrupted and a modern breast care service platform was established in a private sector health care facility in the DRC.

Impact of antiviral AV2 in the topical treatment of HPV-associated lesions of the cervix: Results of a phase III randomized placebo-controlled trial.

BACKGROUND: Non-surgical topical therapies have been assessed in the treatment of precancerous lesions of the cervix. Their use can offer logistical and feasibility advantages in low-resource settings. Antiviral AV2® is a mixture of natural essential oils (eugenol, carvone, nerolidol, geraniol) in olive oil, and has a broad spectrum anti-viral activity. In a phase II randomized controlled trial (RCT), AV2® proved effective in reducing the size of cervical lesions associated with human papillomavirus (HPV). The purpose of the present study was to further evaluate the efficacy of AV2 over placebo in the topical treatment of HPV-associated cervical lesions. METHODS: Women aged 25 years and older were included in this phase 3 RCT. Cytology screening, HPV testing and visual inspection of the cervix with 5% acetic acid (VIA) were performed on all participants. VIA-positive women were randomized to one of two groups to receive treatment by either AV2® or placebo. The treatment consisted of 2 puffs of spray of the investigational drug directed to the cervix. Participants were subjected to repeat examinations two months and six months later for assessment of outcomes. The primary outcome was the change of lesions on VIA at 2 months after application of the investigational drug. Secondary outcomes were: HPV clearance and cytologic regression at 2 months and 6 months, and number of participants with AEs. RESULTS: A total 327 VIA positive women were randomized in two groups (168 in AV2 group and 159 in placebo group). Women in the 2 groups were similar with respect to baseline demographics and clinical characteristics. At 2 months, regression of lesions on VIA was observed in 127 (89.4%) out of 142 women in AV2 group compared to 120 (91.6%) out of 131 women in placebo group (P = 0.7). On cytology, regression of lesions occurred in 14 (56%) out of 25 women in the AV2 arm and in 13 (48.1) out of 27 women in the placebo arm (p = 0.7), and HPV clearance rates were 34.1% and 35% in AV2 group and placebo group respectively (p = 0.8). At 6 months cytologic regression was observed in 64.7% of women in AV2 group and 45.8% in placebo group (p = 0.2), while HPV clearance occurred in 11 (51.9%) out of 17 women in AV2 arm versus 11 (34.4%) in placebo arm (p = 0.3).Some local side effects (burning, itching, irritation) were similarly noted in the 2 groups (p-values = 0.169, 0.623 and 0.172 respectively) but they were mild and transitory. CONCLUSION: A topical application of AV2 onto the cervix can induce the regression of cervical precancerous lesions, but its efficacy does not significantly differ with that of placebo. The discrepancy between the expected and the recorded sample size as well as the huge number of lost to follow-up probably impeded the power of analyses, which could be one of the reasons for the lack of difference seen between AV2 and placebo. Further evaluation of the effects of AV2 with different diagnostic methods and treatment regimen and arms is warranted. CLINICAL TRIAL REGISTRATION: NCT02346227 registered on November 8, 2014.

Efficacy of commercially available biological agents for the topical treatment of cervical intraepithelial neoplasia: a systematic review.

BACKGROUND: Cervical cancer is a major public health issue in the world, especially in developing countries. It can be prevented through vaccination against HPV (primary prevention) and through screening and treatment of cervical intraepithelial neoplasia (CIN) (secondary prevention). Surgical methods for treatment of CIN are linked to complications such as bleeding and adverse pregnancy outcomes. Furthermore, these methods are not generally available in resource-poor settings. Therefore, topical agents for local application on the cervix have been used since decades to overpass complications and limitations of the surgical methods. AIMS: Review of the literature on the efficacy of commercially available biological agents used for topical treatment of cervical intraepithelial neoplasia (CIN). METHODS: A systematic search through PubMed and the Cochrane database was performed up to December 2017, using the medical subheadings (MesH) for topical agent, treatment, and cervical intraepithelial neoplasia. Appropriate inclusion/exclusion criteria have been used for the selection of eligible clinical studies. Clinical studies containing a minimum of 20 women, aged 18-50 with a diagnosis of CIN 1-3, and at least a 4 weeks follow-up after the end of the topical treatment were included. RESULTS: The initial electronic database search resulted in a total of 849 articles. After screening titles and abstracts, 62 articles were selected as potential studies. Of these, six articles were included in the review after reading the full text: two were on 5-FluoroUracil, two on trans retinoic acid, one on Imiquimod, and one on Cidofovir. The reported regression/remission rates for CIN differed among studies. In CIN2 patients, the overall remission rate ranged between 43 and 93% for the active agents. CONCLUSION: Among the topical agents studied, 5-FluoroUracil showed good remission rates above 80%. Varying results seen in this review is due to the differences in quality of the design between studies. Large-scale and less biaised studies are needed to elucidate the true efficacy and safety of topical agents in the treatment of CIN.

Prevalence and Distribution of Human Papillomavirus Genotypes Among Women in Kinshasa, The Democratic Republic of the Congo.

PURPOSE: Cervical cancer is the leading cause of mortality by cancer in sub-Saharan Africa. The human papillomavirus (HPV) infection is recognized as a necessary and sufficient cause for cervical cancer. Population-specific estimates of HPV prevalence in the Democratic Republic of the Congo (DRC) are unknown. This study aims to estimate the prevalence of HPV and identify predominant genotypes circulating in Kinshasa, DRC. METHODS: Between July 2015 and July 2017, women were invited to attend a screening program at Mont-Amba Health Centre in Kinshasa. Cervical specimens were collected using the Preservcyt medium. HPV DNA testing was performed for all specimens using real-time polymerase chain reaction. RESULTS: During the 2-year period, a total of 1,870 women age 25 to 82 years were screened. The mean age was 46 years (± 11.4 years). The overall HPV prevalence was 28.2% (95% CI, 26.1% to 30.3%). High-risk HPV prevalence was 24.8% (95% CI, 22.8% to 26.8%). Women younger than 30 years had the highest overall HPV prevalence (42.2%; 95% CI, 34.7% to 49.9%). A second peak of prevalence was observed in women age 60 years and older. HPV68 (5.5%; 95% CI, 4.5% to 6.6%) was the most prevalent HPV type. CONCLUSION: The distribution of HPV genotypes among women in our population was different compared with other world regions. A key finding was that HPV68 was the most prevalent high-risk HPV genotype. These findings highlight the need for the determination in our population of the etiologic fraction of different HPV types in invasive cervical cancers.

Efficacy of antiviral drug AV2 in the treatment of human papillomavirus-associated precancerous lesions of the uterine cervix: A randomized placebo-controlled clinical trial in Kinshasa, DR Congo. (KINVAV study).

BACKGROUND: Cervical Cancer (CC) is a major public health problem in DR Congo; the high incidence of CC is due to the inexistence of effective screening programs based on cytology and/or HPV detection followed by appropriate treatments. This situation highlights the need to implement efficacious and inexpensive treatment methods. This study aims at evaluating the efficacy of a topical antiviral drug named AV2® as a treatment for HPV-associated lesions of the cervix. METHODS: Women will undergo cytology sampling, HPV testing and Visual inspection of the cervix after application of 5% acetic acid (VIA). VIA-positive women will be randomized to one of two groups to receive treatment by either AV2®or placebo. They will undergo control examinations after two months and after six months. In case of persistent lesions on VIA, treatment by cryotherapy will be done. The primary outcomes will be the change of lesions, the clearance of HPV DNA, and the correlation of the two 2 months after treatment with AV2®. CONCLUSION: This study is the first large-scale study in Africa to evaluate systematically the efficacy and safety of a topical antiviral drug for the treatment of HPV- associated lesions of the cervix. Its findings will direct the planning of suitable algorithms for CC screening and treatment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov - Unique identifier: NCT02346227, registered on November 8, 2014.