Multiple High-Risk HPV Types Contribute to Cervical Dysplasia in Ugandan Women Living With HIV on Antiretroviral Therapy.

BACKGROUND: Cervical cancer mortality remains high in sub-Saharan Africa, especially among women living with HIV (WLWH). Characterization of prevalent high-risk human papillomavirus (hrHPV) types and immune function in WLWH with cervical abnormalities despite antiretroviral therapy (ART) can inform prevention strategies. SETTING: Kampala, Uganda. METHODS: From 2017 to 2020, we enrolled Ugandan women with cervical dysplasia detected with visual inspection with acetic acid (VIA). WLWH were required to be on ART >3 months with plasma HIV RNA <1000 copies/mL. Biopsies from VIA-positive lesions underwent histopathologic grading and cervical swab specimens were tested for hrHPV. Clinical correlations were evaluated with Poisson regression to estimate adjusted prevalence ratios (aPR). RESULTS: One hundred eighty-eight WLWH and 116 HIV-seronegative women participated. Among WLWH, median ART duration was 6 years and median CD4 667 cells/µL. Cervical intraepithelial neoplasia (CIN) grade 2/3 was found in 29% of WLWH versus 9% of HIV-seronegative women. In women with CIN1 or without histopathology-confirmed dysplasia, hrHPV (aPR [95% confidence interval]: 2.17 [1.43 to 3.29]) and multiple hrHPV (aPR 3.73 [1.07 to 13.1]) were more common in WLWH, as were vaccine-targeted and vaccine-untargeted hrHPVtypes. Differences in hrHPV prevalence by HIV serostatus were not observed in women with CIN2/3 (interaction P < 0.01). Among WLWH, low CD4/8 ratio was associated with hrHPV while detectable plasma HIV RNA (20-1000 copies/mL) was associated with CIN2/3 or invasive cancer. CONCLUSION: Despite ART, WLWH with cervical VIA abnormalities remain at elevated risk for multiple hrHPV and high-grade dysplasia. Cervical cancer prevention and research tailored for WLWH are warranted in the ART era.

Implementation research to accelerate scale-up of national screen and treat strategies towards the elimination of cervical cancer.

BACKGROUND: Cervical cancer is a significant public health problem, with 570,000 new cases and 300,000 deaths of women per year globally, mostly in low- and middle-income countries. In 2018 the WHO Director General made a call to action for the elimination of cervical cancer as a public health problem. MAIN BODY: New thinking on programmatic approaches to introduce emerging technologies and screening and treatment interventions of cervical precancer at scale is needed to achieve elimination goals. Implementation research (IR) is an important yet underused tool for facilitating scale-up of evidence-based screening and treatment interventions, as most research has focused on developing and evaluating new interventions. It is time for countries to define their specific IR needs to understand acceptability, feasibility, and cost-effectiveness of interventions as to design and ensure effective implementation, scale-up, and sustainability of evidence-based screening and treatment interventions. WHO convened an expert advisory group to identify priority IR questions for HPV-based screening and treatment interventions in population-based programmes. Several international organizations are supporting large scale introduction of screen-and-treat approaches in many countries, providing ideal platforms to evaluate different approaches and strategies in diverse national contexts. CONCLUSION: For reducing cervical cancer incidence and mortality, the readiness of health systems, the reach and effectiveness of new technologies and algorithms for increasing screening and treatment coverage, and the factors that support sustainability of these programmes need to be better understood. Answering these key IR questions could provide actionable guidance for countries seeking to implement the WHO Global Strategy towards cervical cancer elimination.

Surgical candidacy and treatment initiation among women with cervical cancer at public referral hospitals in Kampala, Uganda: a descriptive cohort study.

OBJECTIVES: This study aimed to report the proportion of women with a new diagnosis of cervical cancer recommended for curative hysterectomy as well as associated factors. We also report recommended treatments by stage and patterns of treatment initiation. DESIGN: This was an observational cohort study. Inperson surveys were followed by a phone call. SETTING: Participants were recruited at the two public tertiary care referral hospitals in Kampala, Uganda. PARTICIPANTS: Adult women with a new diagnosis of cervical cancer were eligible: 332 were invited to participate, 268 met the criteria and enrolled, and 255 completed both surveys. PRIMARY AND SECONDARY OUTCOMES MEASURES: The primary outcome of interest was surgical candidacy; a secondary outcome was treatment initiation. Descriptive and multivariate statistical analyses examined the associations between predictors and outcomes. Sensitivity analyses were performed to examine outcomes in subgroups, including stage and availability of radiation. RESULTS: Among 268 participants, 76% were diagnosed at an advanced stage (IIB-IVB). In total, 12% were recommended for hysterectomy. In adjusted analysis, living within 15 km of Kampala (OR 3.10, 95% CI 1.20 to 8.03) and prior screening (OR 2.89, 95% CI 1.22 to 6.83) were significantly associated with surgical candidacy. Radiotherapy availability was not significantly associated with treatment recommendations for early-stage disease (IA-IIA), but was associated with recommended treatment modality (chemoradiation vs primary chemotherapy) for locally advanced stage (IIB-IIIB). Most (67%) had started treatment. No demographic or health factor, treatment recommendation, or radiation availability was associated with treatment initiation. Among those recommended for hysterectomy, 55% underwent surgery. Among those who had initiated treatment, 82% started the modality that was recommended. CONCLUSION: Women presented to public referral centres in Kampala with mostly advanced-stage cervical cancer and few were recommended for surgery. Most were able to initiate treatment. Lack of access to radiation did not significantly increase the proportion of early-stage cancers recommended for hysterectomy.

Evidence-based improvisation: Facing the challenges of cervical cancer care in Uganda.

There is significant disparity in the prevalence of cervical cancer globally, with low- and middle-income countries (LMICs) shouldering a disproportionate share of disease incidence and an even greater proportion of morbidity and mortality. Available resources for diagnosis, treatment and palliation of cervical cancer are inversely related to per capita income. While prevention and screening remain public health priorities, given the large number of women affected by cervical cancer, expanding treatment capacity should be included in any evidence-based intervention plan. Uganda, a country with a high incidence of cervical cancer, serves as a representative case study in terms of the challenges of diagnosis and access to treatment in sub-Saharan Africa. Providers and patients in Uganda are challenged by late presentation to care, limited training opportunities, cost-prohibitive diagnostic studies, insufficient access to gold-standard treatment, and under-utilized palliative care services. This review highlights the ways in which Uganda's experience is typical of the continent at large, as well as areas where Uganda is unique. We describe the ways in which a small but dedicated group of gynecologists carefully use limited evidence and available resources creatively to provide the best possible care for their patients. We show that improvisation, albeit evidence-based, is central to the nature and success of oncology care in Africa (Livingston, 2012). We argue that a "recalibrated global response" (Farmer et al., 2010), particularly stressing the expansion of radiotherapy capabilities, could dramatically improve cancer care and outcomes for women in Uganda as well as in LMICs globally.

Performance of Cervical Cancer Screening Techniques in HIV-Infected Women in Uganda.

OBJECTIVE: Women infected with human immunodeficiency virus (HIV) have a higher risk of HPV infections and developing cervical cancer, thus screening them is imperative. This study was aimed to evaluate and compare the performance of 3 cervical cancer screening options among HIV-infected women in Uganda. MATERIALS AND METHODS: Data from 2,337 Ugandan women who reported their HIV status were obtained from a population-based cervical cancer screening study. Women were offered 3 screening tests: vaginal and cervical careHPV and visual inspection with acetic acid (VIA), and the results were evaluated by HIV status. RESULTS: The prevalence of HIV infection was 16.5%. Women infected with HIV had a higher prevalence of cervical intraepithelial neoplasia grade 2+ (CIN2+) than uninfected women (12.9% vs 1.7%; p < .001). The sensitivity for cervical careHPV among the HIV-infected women was 94.3% compared to 81.3% among the uninfected women. Whereas the sensitivity for vaginal careHPV was also higher among the HIV-infected women, the sensitivity of VIA was higher among the uninfected women. The mean vaginal and cervical careHPV signal strength was higher in the HIV-infected women than in the uninfected women (p < .001). CONCLUSIONS: CareHPV is very sensitive for detecting CIN2+ in HIV-infected women, even using a vaginal sample. The sensitivity of careHPV in HIV-infected women is higher than in HIV-uninfected women. However, additional research is needed to determine the best option for screening and triage of HPV-positive women that can be implemented in low-resource settings, especially among HIV- and HPV-positive women.