Cervical cancer prevention in countries with the highest HIV prevalence: a review of policies.

INTRODUCTION: Cervical cancer (CC) is the leading cause of cancer-related death among women in sub-Saharan Africa. It occurs most frequently in women living with HIV (WLHIV) and is classified as an AIDS-defining illness. Recent World Health Organisation (WHO) recommendations provide guidance for CC prevention policies, with specifications for WLHIV. We systematically reviewed policies for CC prevention and control in sub-Saharan countries with the highest HIV prevalence. METHODS: We included countries with an HIV prevalence ≥ 10% in 2018 and policies published between January 1st 2010 and March 31st 2022. We searched Medline via PubMed, the international cancer control partnership website and national governmental websites of included countries for relevant policy documents. The online document search was supplemented with expert consultation for each included country. We synthesised aspects defined in policies for HPV vaccination, sex education, condom use, tobacco control, male circumcision,cervical screening, diagnosis and treatment of cervical pre-cancerous lesions and cancer, monitoring mechanisms and cost of services to women while highlighting specificities for WLHIV. RESULTS: We reviewed 33 policy documents from nine countries. All included countries had policies on CC prevention and control either as a standalone policy (77.8%), or as part of a cancer or non-communicable diseases policy (22.2%) or both (66.7%). Aspects of HPV vaccination were reported in 7 (77.8%) of the 9 countries. All countries (100%) planned to develop or review Information, Education and Communication (IEC) materials for CC prevention including condom use and tobacco control. Age at screening commencement and screening intervals for WLHIV varied across countries. The most common recommended screening and treatment methods were visual inspection with acetic acid (VIA) (88.9%), Pap smear (77.8%); cryotherapy (100%) and loop electrosurgical procedure (LEEP) (88.9%) respectively. Global indicators disaggregated by HIV status for monitoring CC programs were rarely reported. CC prevention and care policies included service costs at various stages in three countries (33.3%). CONCLUSION: Considerable progress has been made in policy development for CC prevention and control in sub Saharan Africa. However, in countries with a high HIV burden, there is need to tailor these policies to respond to the specific needs of WLHIV. Countries may consider updating policies using the recent WHO guidelines for CC prevention, while adapting them to context realities.

Thermal ablation versus cryotherapy or loop excision to treat women positive for cervical precancer on visual inspection with acetic acid test: pilot phase of a randomised controlled trial.

BACKGROUND: Cryotherapy is standard practice for treating patients with cervical precancer in see-and-treat programmes in low-income and middle-income countries (LMICs). Because of logistical difficulties with cryotherapy (eg, the necessity, costs, and supply chain difficulties of refrigerant gas; equipment failure; and treatment duration >10 min), a battery-operated thermal ablator that is lightweight and portable has been developed. We aimed to compare thermal ablation using the new device with cryotherapy. METHODS: We report the pilot phase of a randomised controlled trial in routine screen-and-treat clinics providing cervical screening using visual inspection with acetic acid (VIA) in Lusaka, Zambia. We recruited non-pregnant women, aged 25 years or older, who were eligible for ablative therapy. We randomly assigned participants (1:1:1) to thermal ablation, cryotherapy, or large loop excision of the transformation zone (LLETZ), using computer-generated allocation. The randomisation was concealed but the nurses providing treatment and the participants were unmasked. Thermal ablation was achieved using the Liger thermal ablator (using 1-5 overlapping applications of the probe heated to 100°C, each application lasting for 40 s), cryotherapy was carried out using the double-freeze technique (freeze for 3 min, thaw for 5 min, and freeze again for 3 min), and LLETZ (using a large loop driven by an electro-surgical unit to excise the transformation zone) was done under local anaesthesia. The primary endpoint was treatment success, defined as either human papillomavirus (HPV) type-specific clearance among participants who were positive for the same HPV type at baseline, or a negative VIA test at 6-month follow-up, if the baseline HPV test was negative. Per protocol analyses were done. Enrolment for the full trial is ongoing. Here, we present findings from a prespecified pilot phase of the full trial. The final analysis of the full trial will assess non-inferiority of the groups for the primary efficacy endpoint. The study is registered with ClinicalTrials.gov, number NCT02956239. FINDINGS: Between Aug 2, 2017, and Jan 15, 2019, 750 participants were randomly assigned (250 per group). 206 (84%) participants in the cryotherapy group, 197 (81%) in the thermal ablation group, and 204 (84%) in the LLETZ group attended the 6-month follow-up examination. Treatment success was reported in 120 (60%) of 200 participants in the cryotherapy group, 123 (64%) of 192 in the thermal ablation group, and 134 (67%) of 199 in the LLETZ group (p=0·31). Few participants complained of moderate to severe pain in any group immediately after the procedure (six [2%] of 250 in the cryotherapy group, four [2%] of 250 in the thermal ablation group, and five [2%] of 250 in the LLETZ group) and 2 weeks after the procedure (one [<1%] of 241 in the cryotherapy group, none of 242 in the thermal ablation group, and two [<1%] of 237 in the LLETZ group). None of the participants reported any complication requiring medical consultation or admission to hospital. INTERPRETATION: Results from this pilot study preliminarily suggest that thermal ablation has similar treatment success to cryotherapy, without the practical disadvantages of providing cryotherapy in an LMIC. However, the study was not powered to establish the similarity between the techniques, and results from the ongoing randomised controlled trial are need to confirm these results. FUNDING: US National Institutes of Health.

Developing institutions for cancer care in low-income and middle-income countries: from cancer units to comprehensive cancer centres.

Global cancer centres operate across different sizes, scales, and ecosystems. Understanding the essential aspects of the creation, organisation, accreditation, and activities within these settings is crucial for developing an affordable, equitable, and quality cancer care, research, and education system. Robust guidelines are scarce for cancer units, cancer centres, and comprehensive cancer centres in low-income and middle-income countries. However, some robust examples of the delivery of complex cancer care in centres in emerging economies are available. Although it is impossible to create an optimal system to fit the unique needs of all countries for the delivery of cancer care, we summarise what has been published about the development and management of cancer centres in low-income and middle-income countries so far and highlight the need for clinical and political leadership.

Clinical Performance Validation of 4 Point-of-Care Cervical Cancer Screening Tests in HIV-Infected Women in Zambia.

OBJECTIVES: We sought to determine the clinical performance of visual inspection with acetic acid (VIA), digital cervicography (DC), Xpert human papillomavirus (HPV), and OncoE6 for cervical cancer screening in an HIV-infected population. MATERIALS AND METHODS: HIV-infected women 18 years or older were included in this cross-sectional validation study conducted in Lusaka, Zambia. The screening tests were compared against a histological gold standard. We calculated sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and odds ratios using cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) and grade 3 or worse (CIN 3+) thresholds. RESULTS: Between January and June 2015, a total of 200 women were enrolled. Fifteen percent were screen positive by VIA, 20% by DC, 47% by Xpert HPV, and 6% by OncoE6. Using a CIN 2+ threshold, the sensitivity and specificity of VIA were 48% (95% CI = 30%-67%) and 92% (95% CI = 86%-95%), respectively. Similarly, the sensitivity and specificity of DC were 59% (95% CI = 41%-76%) and 88% (95% CI = 82%-93%), respectively. The sensitivity and specificity of Xpert HPV were 88% (95% CI = 71%-97%) and 60% (95% CI = 52%-68%), respectively. Finally, the sensitivity and specificity of OncoE6 were 31% (95% CI = 16%-50%) and 99% (95% CI = 97%-100%), respectively. CONCLUSIONS: VIA and DC displayed moderate sensitivity and high specificity. Xpert HPV performed equivalently to currently approved HPV DNA tests, with high sensitivity and moderate specificity. OncoE6 displayed excellent specificity but low sensitivity. These results confirm an important role for VIA, DC, and Xpert HPV in screen-and-treat cervical cancer prevention in low- and middle-income countries, such as Zambia.

The burden of cervical pre-cancer and cancer in HIV positive women in Zambia: a modeling study.

BACKGROUND: HIV infection is associated with a higher incidence of precancerous cervical lesions and their progression to invasive cervical cancer (ICC). Zambia is a global epicenter of HIV and ICC, yet the overall burden of cervical pre-cancer [cervical intraepithelial neoplasia 3 (CIN3)] and ICC among its HIV positive adult female population is unknown. The objective of this study was to determine the burden of cervical disease among HIV positive women in Zambia by estimating the number with CIN3 and ICC. METHODS: We conducted a cross-sectional study among 309 HIV positive women attending screening in Lusaka (Zambia's most populated province) to measure the cervical disease burden by visual inspection with acetic acid enhanced by digital cervicography (DC), cytology, and histology. We then used estimates of the prevalence of CIN3 and ICC from the cross-sectional study and Spectrum model-based estimates for HIV infection among Zambian women to estimate the burden of CIN3 and ICC among HIV positive women nationally. RESULTS: Over half (52 %) of the study participants screened positive by DC, while 45 % had cytologic evidence of high grade squamous intraepithelial lesions (SIL) or worse. Histopathologic evaluation revealed that 20 % of women had evidence of CIN2 or worse, 11 % had CIN3 or worse, and 2 % had ICC. Using the Spectrum model, we therefore estimate that 34,051 HIV positive women in Zambia have CIN3 and 7,297 have ICC. CONCLUSIONS: The DC, cytology, and histology results revealed a large cervical disease burden in this previously unscreened HIV positive population. This very large burden indicates that continued scale-up of cervical cancer screening and treatment is urgently needed.

Identification of human papillomaviruses from formalin-fixed, paraffin-embedded pre-cancer and invasive cervical cancer specimens in Zambia: a cross-sectional study.

BACKGROUND: The most common human papillomavirus (HPV) genotypes isolated from cervical cancer in select African countries are HPV-16, HPV-18, HPV-35, and HPV-45, but the most common genotypes in Zambia are unknown. The overall objective of this study was to assess the potential impact of current HPV vaccines in preventing cervical cancer in Zambia, by determining the combined prevalence of HPV-16 and/or HPV-18 in invasive cervical cancer (ICC) and high-grade pre-cancer [cervical intraepithelial neoplasia 2 or 3 (CIN2/3)] cases. FINDINGS: We compared DNA extraction techniques to determine which assay performs well in the Zambian context, where unbuffered formalin is used to fix specimens. We then tested specimens with the Abbott RealTime High-Risk HPV test to estimate the prevalence of HPV-16/18 in formalin-fixed, paraffin-embedded ICC and CIN2/3 specimens. DNA extraction using heat (without xylene) was more successful than xylene-based extraction. Over 80% of specimens tested using heat extraction and the Abbott RealTime HPV test were positive for HPV. HPV-16 and/or HPV-18 were identified in 65/93 (69.9%) ICC specimens positive for HPV and in 38/65 (58.5%) CIN2/3 specimens positive for HPV. CONCLUSIONS: To our knowledge this is the first report to identify HPV genotypes in cervical cancers in Zambia. A combined HPV-16/18 prevalence of 69.9% in ICC specimens suggests that current vaccines will be highly protective against cervical cancer in Zambia.

Preference for human papillomavirus-based cervical cancer screening: results of a choice-based conjoint study in Zambia.

OBJECTIVE: The objective of this study was to assess the conditions under which Zambian women with a history of cervical cancer screening by visual inspection with acetic acid might switch to human papillomavirus-based testing in the future. MATERIALS AND METHODS: We conducted a choice-based conjoint survey in a sample of women recently screened by visual inspection in Lusaka, Zambia. The screening attribute considered in hypothetical-choice scenarios included screening modality, sex and age of the examiner, whether screening results would be presented visually, distance from home to the clinic, and wait time for results. RESULTS: Of 238 women in the sample, 208 (87.4%) provided responses sufficiently reliable for analysis. Laboratory testing on a urine sample was the preferred screening modality, followed by visual screening, laboratory testing on a self-collected vaginal specimen, and laboratory testing on a nurse-collected cervical specimen. Market simulation suggested that only 39.7% (95% CI = 33.8-45.6) of the respondents would prefer urine testing offered by a female nurse in her 30s over visual inspection of the cervix conducted by a male nurse in his 20s if extra wait time were as short as 1 hour and the option of viewing how their cervix looks like were not available. CONCLUSIONS: Our study suggests that, for some women, the level of preference for human papillomavirus-based screening strategies may depend highly on the process and conditions of service delivery.

The Effect of Cryotherapy on Human Papillomavirus Clearance Among HIV-Positive Women in Lusaka, Zambia.

OBJECTIVE: We sought to investigate the progression of human papillomaviruses (HPV) infection in HIV-positive women after cryotherapy. METHODS: We examined changes in detection of high-risk HPV (hrHPV) cervical infections among HIV-infected women over a 12-week period after cryotherapy using stored specimens from a cohort study conducted between June 2009 and March 2011 in Lusaka, Zambia. Samples from visits at baseline and weeks 4, 8, and 12 were tested using the Roche Linear Array assay. RESULTS: A total of 89 women were included in the analysis. The median age was 32 years (interquartile range [IQR], 28-36 years). The median CD4+ cell count was 350 cells/µL (IQR, 214-470 cells/µL), and 66% of women were receiving antiretroviral therapy. At baseline, the prevalence of hrHPV was 91% (95% confidence interval [CI], 83%-95%). HPV45 was the most common HPV type, present in (30%) women, followed by HPV16 (27%), HPV18 (27%), HPV51 (20%), and HPV58 (22%). Among women with valid results both at baseline and 12 weeks, 25% (17/67) cleared their initial hrHPV infection within 12 weeks of treatment, although 65% (11/17) had new hrHPV types detected. CONCLUSIONS: Cryotherapy led to clearance of 25% of hrHPV infections within 12 weeks of treatment. However, hrHPV infection remained persistent in most women, and new hrHPV types were detected often, explaining the high rate of persistence and recurrence of cervical disease in this population. Continued efforts to scale up HPV vaccination and cervical screening should remain a priority in high HIV burden settings such as Zambia.

Selecting and Tailoring Implementation Strategies to Improve Human Papillomavirus Vaccine Uptake in Zambia: A Nominal Group Technique Approach.

The human papillomavirus (HPV) vaccine is effective in cervical cancer prevention. However, many barriers to uptake exist and strategies to overcome them are needed. Therefore, this study aimed to select and tailor implementation strategies to barriers identified by multiple stakeholders in Zambia. The study was conducted in Lusaka district between January and February 2023. Participants were purposively sampled from three stakeholder groups namely, adolescent girls, parents, and teachers and healthcare workers. With each of the stakeholders' groups (10-13 participants per group), we used the nominal group technique to gain consensus to tailor feasible and acceptable implementation strategies for mitigating the identified contextual barriers. The identified barriers included low levels of knowledge and awareness about the HPV vaccine, being out of school, poor community sensitisation, lack of parental consent to vaccinate daughters, and myths and misinformation about the HPV vaccine. The lack of knowledge and awareness of the HPV vaccine was a common barrier across the three groups. Tailored strategies included conducting educational meetings and consensus-building meetings, using mass media, changing service sites, re-examining implementation, and involving patients/consumers and their relatives. Our study contributes to the available evidence on the process of selecting and tailoring implementation strategies to overcome contextual barriers. Policymakers should consider these tailored strategies to mitigate barriers and improve HPV vaccine uptake.

A portable thermal ablation device for cervical cancer prevention in a screen-and-treat setting: a randomized, noninferiority trial.

Implementing standard-of-care cryotherapy or electrosurgical excision to treat cervical precancers is challenging in resource-limited settings. An affordable technological alternative that is as effective as standard-of-care techniques would greatly improve access to treatment. This randomized controlled trial aims to demonstrate the noninferiority efficacy of a portable, battery-driven thermal ablation (TA) device compared to cryotherapy and electrosurgical excision (large loop excision of transformation zone (LLETZ)) to treat cervical precancer in a screen-and-treat program in Zambia. A total of 3,124 women positive on visual inspection with acetic acid and eligible for ablative therapy were randomized to one of the treatment arms. Human papillomavirus (HPV) testing was performed at baseline and at the follow-up. The primary outcome was treatment success, defined as either type-specific HPV clearance at the follow-up in participants positive for HPV at baseline, or a negative visual inspection with acetic acid test for those who had a negative HPV test at baseline. After a median follow-up of 12 months, treatment success rates were 74.0%, 71.1% and 71.4% for the TA, cryotherapy and LLETZ arms, respectively, thus demonstrating noninferiority (P = 0.83). TA was a safe and well-accepted procedure. Only 3.6% of those randomized to TA reported moderate-to-severe pain, compared to 6.5% and 1.9% for the cryotherapy and LLETZ arms, respectively. Thus, our randomized controlled trial demonstrates the safety and efficacy of TA, which is not inferior to cryotherapy or surgical excision.ClinicalTrials.gov registration: NCT02956239 .

Internal Validation of Automated Visual Evaluation (AVE) on Smartphone Images for Cervical Cancer Screening in a Prospective Study in Zambia.

Objectives: Visual inspection with acetic acid (VIA) is a low-cost approach for cervical cancer screening used in most low- and middle-income countries (LMICs) but, similar to other visual tests like histopathology, is subjective and requires sustained training and quality assurance. We developed, trained, and validated an artificial-intelligence-based "Automated Visual Evaluation" (AVE) tool that can be adapted to run on smartphones to assess smartphone-captured images of the cervix and identify precancerous lesions, helping augment performance of VIA. Design: Prospective study. Setting: Eight public health facilities in Zambia. Participants: 8,204 women aged 25-55. Interventions: Cervical images captured on commonly used low-cost smartphone models were matched with key clinical information including human immunodeficiency virus (HIV) and human papillomavirus (HPV) status, plus histopathology analysis (where applicable), to develop and train an AVE algorithm and evaluate its performance for use as a primary screen and triage test for women who are HPV positive. Main outcome measures: Area under the receiver operating curve (AUC); sensitivity; specificity. Results: As a general population screening for cervical precancerous lesions, AVE identified cases of cervical precancerous and cancerous (CIN2+) lesions with high performance (AUC = 0.91, 95% confidence interval [CI] = 0.89 to 0.93), which translates to a sensitivity of 85% (95% CI = 81% to 90%) and specificity of 86% (95% CI = 84% to 88%) based on maximizing the Youden's index. This represents a considerable improvement over VIA, which a meta-analysis by the World Health Organization (WHO) estimates to have sensitivity of 66% and specificity of 87%. For women living with HIV, the AUC of AVE was 0.91 (95% CI = 0.88 to 0.93), and among those testing positive for high-risk HPV types, the AUC was 0.87 (95% CI = 0.83 to 0.91). Conclusions: These results demonstrate the feasibility of utilizing AVE on images captured using a commonly available smartphone by screening nurses and support our transition to clinical evaluation of AVE's sensitivity, specificity, feasibility, and acceptability across a broader range of settings. The performance of the algorithm as reported may be inflated, as biopsies were obtained only from study participants with visible aceto-white cervical lesions, which can lead to verification bias; and the images and data sets used for testing of the model, although "unseen" by the algorithm during training, were acquired from the same set of patients and devices, limiting the study to that of an internal validation of the AVE algorithm.

Internal validation of Automated Visual Evaluation (AVE) on smartphone images for cervical cancer screening in a prospective study in Zambia.

OBJECTIVES: Visual inspection with acetic acid (VIA) is a low-cost approach for cervical cancer screening used in most low- and middle-income countries (LMICs) but, similar to other visual tests, is subjective and requires sustained training and quality assurance. We developed, trained, and validated an artificial-intelligence-based "Automated Visual Evaluation" (AVE) tool that can be adapted to run on smartphones to assess smartphone-captured images of the cervix and identify precancerous lesions, helping augment VIA performance. DESIGN: Prospective study. SETTING: Eight public health facilities in Zambia. PARTICIPANTS: A total of 8204 women aged 25-55. INTERVENTIONS: Cervical images captured on commonly used low-cost smartphone models were matched with key clinical information including human immunodeficiency virus (HIV) and human papillomavirus (HPV) status, plus histopathology analysis (where applicable), to develop and train an AVE algorithm and evaluate its performance for use as a primary screen and triage test for women who are HPV positive. MAIN OUTCOME MEASURES: Area under the receiver operating curve (AUC); sensitivity; specificity. RESULTS: As a general population screening tool for cervical precancerous lesions, AVE identified cases of cervical precancerous and cancerous (CIN2+) lesions with high performance (AUC = 0.91, 95% confidence interval [CI] = 0.89-0.93), which translates to a sensitivity of 85% (95% CI = 81%-90%) and specificity of 86% (95% CI = 84%-88%) based on maximizing the Youden's index. This represents a considerable improvement over naked eye VIA, which as per a meta-analysis by the World Health Organization (WHO) has a sensitivity of 66% and specificity of 87%. For women living with HIV, the AUC of AVE was 0.91 (95% CI = 0.88-0.93), and among those testing positive for high-risk HPV types, the AUC was 0.87 (95% CI = 0.83-0.91). CONCLUSIONS: These results demonstrate the feasibility of utilizing AVE on images captured using a commonly available smartphone by nurses in a screening program, and support our ongoing efforts for moving to more broadly evaluate AVE for its clinical sensitivity, specificity, feasibility, and acceptability across a wider range of settings. Limitations of this study include potential inflation of performance estimates due to verification bias (as biopsies were only obtained from participants with visible aceto-white cervical lesions) and due to this being an internal validation (the test data, while independent from that used to develop the algorithm was drawn from the same study).

Implementation Strategies Used to Increase Human Papillomavirus Vaccination Uptake by Adolescent Girls in Sub-Saharan Africa: A Scoping Review.

Barriers to successful implementation of the human papillomavirus vaccination exist. However, there is limited evidence on implementation strategies in sub-Saharan Africa (SSA). Therefore, this scoping review aimed to identify implementation strategies used in SSA to increase HPV vaccination uptake for adolescent girls. This scoping review was guided by Joanna Briggs Institute guidelines for scoping reviews and an a priori protocol and reported based on the Preferred Reporting Items for Systematic Reviews and Metanalysis for Scoping Reviews (PRISMA-ScR). We searched PubMed, EMBASE, CINAHL, Scopus, Google Scholar, and gray literature. Two independent reviewers screened article titles and abstracts for possible inclusion, reviewed the full text, and extracted data from eligible articles using a structured data charting table. We identified strategies as specified in the Expert Recommendation for Implementing Change (ERIC) and reported their importance and feasibility. We retrieved 246 articles, included 28 of these, and identified 63 of the 73 ERIC implementation strategies with 667 individual uses, most of which were highly important and feasible. The most frequently used discrete strategies included the following: Build a coalition and change service sites 86% (24/28), distribute educational materials and conduct educational meetings 82% (23/28), develop educational materials, use mass media, involve patients/relatives and families, promote network weaving and stage implementation scale up 79% (22/28), as well as access new funding, promote adaptability, and tailor strategies 75% (21/28). This scoping review shows that implementation strategies of high feasibility and importance were frequently used, suggesting that some strategies may be cross-cutting, but should be contextualized when planned for use in any region.

Correlates of Parental Consent to Human Papillomavirus Vaccine Uptake by Their Adolescent Daughters in ZAMBIA: Application of the Health Belief Model.

Parental consent for adolescent human papillomavirus (HPV) vaccine uptake is important; however, refusal is prevalent. Therefore, this study aimed to understand factors associated with parental consent for their adolescent daughter's HPV vaccination. A cross-sectional study was conducted in Lusaka, Zambia, between September and October 2021. We recruited parents from different social settings. The means and standard deviations or median and interquartile ranges were used as appropriate to summarise continuous variables. Simple and multiple logistic regression models were fitted with robust estimation of standard errors. The odds ratios are presented with 95% CI. Mediation analysis was conducted using a generalised structural equation model. The study enrolled 400 parents, mean age 45.7 years [95% CI, 44.3-47.1]. Two hundred and fifteen (53.8%) parents reported consenting to their daughters' HPV vaccination, and their daughters received it. None of the health belief model (HBM) construct scores showed an independent association with parental consent. Higher, compared to lower wealth index (AOR; 2.32, 95% CI: 1.29-4.16), knowing someone with genital warts (AOR = 2.23, 95 CI: 1.04-4.76), cervical cancer screening uptake (AOR = 1.93, 95% CI: 1.03-3.62) were associated with increased odds of parental consent. This study highlights factors influencing parental consent for their daughters' HPV vaccination. Ongoing sensitisation programs are important to improve their decision-making.

"When you get the HPV vaccine, it will prevent cervical cancer; it will act as a shield": adolescent girls' knowledge and perceptions regarding the human papillomavirus vaccine in Zambia.

Introduction: The human papillomavirus (HPV) vaccination is an important preventive measure for HPV-related conditions such as cervical cancer. In 2019, Zambia introduced a free national HPV vaccination program for 14-year-old girls. However, the adolescents' knowledge and perceptions regarding the HPV vaccine are not well understood. Therefore, this study aimed to understand adolescent girls' knowledge and perceptions regarding the HPV vaccine and discuss its acceptability and uptake implications. Methods: We conducted a qualitative study in the Lusaka district between June 2021 and November 2021 using semi-structured interviews with adolescent girls aged 15-18 years regardless of their HPV vaccination status. Interviews were transcribed verbatim, and NVIVO 12 was used for data management and analysis. We coded transcripts deductively and inductively based on emerging themes. Perceptions were coded using the health belief model constructs. Results: We interviewed 30 adolescent girls to reach saturation. Seventeen girls reported having received at least one dose of the HPV vaccine. Participants expressed variable knowledge and awareness about HPV and the HPV vaccine. Participants exhibited positive attitudes towards the HPV vaccine and perceived it as beneficial. However, there were multiple perceived barriers to vaccination, such as the need for parental consent, not being in school, concerns about vaccine side effects, and belief in myths and misinformation. Conclusion: The adolescent girls in this study showed variable knowledge and positive attitudes toward the HPV vaccine despite the many perceived barriers. To support increased HPV vaccine acceptability and uptake among adolescent girls in Zambia, it is critical to actively engage stakeholders involved in HPV vaccination, such as adolescents and their parents, and debunk myths and misconceptions about HPV vaccination. Health education in schools and communities should be implemented to increase knowledge about HPV and HPV vaccination among adolescents and their parents.

Determinants of the Implementation of Human Papillomavirus Vaccination in Zambia: Application of the Consolidated Framework for Implementation Research.

Cervical cancer can be prevented, primarily by the administration of the human papillomavirus (HPV) vaccine. Healthcare workers (HCWs) and teachers play important roles when schools are used for vaccine delivery; however, challenges exist. This study aimed to understand the barriers and facilitators to HPV vaccination that are perceived by HCWs and teachers. Guided by the consolidated framework for implementation research (CFIR), key informant interviews were conducted in Lusaka district between June 2021 and November 2021 using a semi-structured questionnaire. Recorded interviews were transcribed verbatim and imported into NVIVO 12 for data management and analysis. We coded transcripts inductively and deductively based on the adapted CFIR codebook. We reached saturation with 23 participants. We identified barriers and facilitators across the five CFIR domains. Facilitators included offering the HPV vaccine free of charge, HPV vaccine effectiveness, stakeholder engagement, and timely planning of the HPV vaccination. Barriers included vaccine mistrust due to its perceived novelty, low levels of parental knowledge, myths and misinformation about the vaccine, lack of parental consent to vaccinate daughters, lack of transport for vaccination outreach, lack of staff incentives, and inadequate sensitisation. Using the CFIR as a guiding framework, we have identified implementation barriers and facilitators to HPV vaccination among HCWs and teachers. Most of the identified barriers are modifiable, hence it is prudent that these are addressed for a high HPV vaccine uptake.

Accuracy of screening tests for cervical pre-cancer in women living with HIV in low-resource settings: a paired prospective study in Lusaka, Zambia.

Introduction: To provide evidence to improve cervical screening for women living with HIV (WLHIV), we assessed the accuracy of screening tests that can be used in low-resource settings and give results at the same visit. Methods: We conducted a paired, prospective study among consecutive eligible WLHIV, aged 18-65 years, receiving cervical cancer screening at one hospital in Lusaka, Zambia. The histopathological reference standard was multiple biopsies taken at two time points. The target condition was high-grade cervical intraepithelial neoplasia (CIN2+). The index tests were high-risk human papillomavirus detection (hrHPV, Xpert HPV, Cepheid), portable colposcopy (Gynocular, Gynius), and visual inspection with acetic acid (VIA). Accuracy of stand-alone and test combinations were calculated as the point estimate with 95% confidence intervals. A sensitivity analysis considered disease when only visible lesions were biopsied. Results: Among 371 participants with histopathological results, 27% (101/371) women had CIN2+ and 23% (23/101) was not detected by any index test. Sensitivity and specificity for stand-alone tests were: hrHPV, 67.3% (95% CI: 57.7-75.7) and 65.3% (59.4-70.7); Gynocular 51.5% (41.9-61.0) and 80.0% (74.8-84.3); and VIA 22.8% (15.7-31.9) and 92.6% (88.8-95.2), respectively. The combination of hrHPV testing followed by Gynocular had the best balance of sensitivity (42.6% [33.4-52.3]) and specificity (89.6% [85.3-92.7]). All test accuracies improved in sensitivity analysis. Conclusion: The low accuracy of screening tests assessed might be explained by our reference standard, which reduced verification and misclassification biases. Better screening strategies for WLHIV in low-resource settings are urgently needed. Registration number: The trial was registered prospectively at ClinicalTrials.gov (ref: NCT03931083 ). The study protocol has been previously published, and the statistical analysis plan can be accessed on ClinicalTrials.gov . Key messages: What is already known on this topic: The 2021 World Health Organization guidelines recommend that women living with HIV (WLHIV) receive screening for high risk human papillomavirus high-risk human papillomavirus (hrHPV) genotypes at three- to five-year intervals, followed by a triage test to determine whether treatment is needed but this is based on low and moderate certainty evidence.What this study adds: This study among WLHIV in Lusaka, Zambia evaluated three screening tests that allow same-day treatment; hrHPV test, portable colposcopy (Gynocular), and visual inspection with acetic acid (VIA), using strict methods to reduce verification and misclassification biases. The test accuracy of the different screening was poor, with sensitivities and specificity for stand-alone tests: hrHPV, 67.3% and 65.3%; Gynocular 51.5% and 80.0%; and VIA 22.8% and 92.6%; respectively.How this study might affect research, practice or policy: Our findings have implications for research and cervical cancer screening policies among WLHIV if test-accuracy in this high-risk population has been overestimated from a majority of exsisting studies that are affected by verification and misclassification biases. Methodologically robust studies are crucial to inform cervical cancer screening practices and policies for the successful implementation of a cervical cancer elimination plan in sub-Saharan Africa, where 85% of women with cervical cancer and HIV live.

Virtual reality and surgical oncology.

More than 80% of people diagnosed with cancer will require surgery. However, less than 5% have access to safe, affordable and timely surgery in low- and middle-income countries (LMICs) settings mostly due to the lack of trained workforce. Since its creation, virtual reality (VR) has been heralded as a viable adjunct to surgical training, but its adoption in surgical oncology to date is poorly understood. We undertook a systematic review to determine the application of VR across different surgical specialties, modalities and cancer pathway globally between January 2011 and 2021. We reviewed their characteristics and respective methods of validation of 24 articles. The results revealed gaps in application and accessibility of VR with a proclivity for high-income countries and high-risk, complex oncological surgeries. There is a lack of standardisation of clinical evaluation of VR, both in terms of clinical trials and implementation science. While all VR illustrated face and content validity, only around two-third exhibited construct validity and predictive validity was lacking overall. In conclusion, the asynchrony between VR development and actual global cancer surgery demand means the technology is not effectively, efficiently and equitably utilised to realise its surgical capacity-building potential. Future research should prioritise cost-effective VR technologies with predictive validity for high demand, open cancer surgeries required in LMICs.

Validation in Zambia of a cervical screening strategy including HPV genotyping and artificial intelligence (AI)-based automated visual evaluation.

BACKGROUND: WHO has recommended HPV testing for cervical screening where it is practical and affordable. If used, it is important to both clarify and implement the clinical management of positive results. We estimated the performance in Lusaka, Zambia of a novel screening/triage approach combining HPV typing with visual assessment assisted by a deep-learning approach called automated visual evaluation (AVE). METHODS: In this well-established cervical cancer screening program nested inside public sector primary care health facilities, experienced nurses examined women with high-quality digital cameras; the magnified illuminated images permit inspection of the surface morphology of the cervix and expert telemedicine quality assurance. Emphasizing sensitive criteria to avoid missing precancer/cancer, ~ 25% of women screen positive, reflecting partly the high HIV prevalence. Visual screen-positive women are treated in the same visit by trained nurses using either ablation (~ 60%) or LLETZ excision, or referred for LLETZ or more extensive surgery as needed. We added research elements (which did not influence clinical care) including collection of HPV specimens for testing and typing with BD Onclarity™ with a five channel output (HPV16, HPV18/45, HPV31/33/52/58, HPV35/39/51/56/59/66/68, human DNA control), and collection of triplicate cervical images with a Samsung Galaxy J8 smartphone camera™ that were analyzed using AVE, an AI-based algorithm pre-trained on a large NCI cervical image archive. The four HPV groups and three AVE classes were crossed to create a 12-level risk scale, ranking participants in order of predicted risk of precancer. We evaluated the risk scale and assessed how well it predicted the observed diagnosis of precancer/cancer. RESULTS: HPV type, AVE classification, and the 12-level risk scale all were strongly associated with degree of histologic outcome. The AVE classification showed good reproducibility between replicates, and added finer predictive accuracy to each HPV type group. Women living with HIV had higher prevalence of precancer/cancer; the HPV-AVE risk categories strongly predicted diagnostic findings in these women as well. CONCLUSIONS: These results support the theoretical efficacy of HPV-AVE-based risk estimation for cervical screening. If HPV testing can be made affordable, cost-effective and point of care, this risk-based approach could be one management option for HPV-positive women.

Gynaecologic oncology surgical cancellations in Zambia.

Introduction: Cancellations of elective surgery in low-and middle-income countries (LMIC) are common and a major hindrance for patients who are in need of surgical therapeutic modalities. This is especially important in the context of scaling up needed surgical interventions for gynaecological cancer care. There is a knowledge gap in the literature related to cancellation of gynaecologic oncology surgeries in LMIC, where there is enormous need for this specific cancer surgical capacity. We report in an observational descriptive fashion, our experience at the UTH/CDH in Lusaka, Zambia, on the causes of surgical cancellations in gynaecologic oncology. Methods: From January 1, 2021 through June 31, 2023, we retrospectively evaluated the surgical registry for gynaecologic oncology at the UTH/CDH in Lusaka, Zambia to assess the number and causes of surgical cancellations. Results: There were a total of 66 (16.96%) surgical cancellations out of 389 scheduled gynaecologic oncology cases. Lack of available blood and/or low haemoglobin was the most frequent cause of surgical cancellations, 27 cases (40.90%). Conclusion: We highlight in our series that the lack of blood, leading to surgical cancellations was the most frequent impediment related to performing scheduled gynaecologic oncology surgical procedures. As gynaecologic oncology services scale up in LMIC, given the radical nature of surgery and its association with blood loss, it is incumbent on the entire clinical ecosystem to address this issue and to develop mitigating strategies, specific to their respective resource setting.