Evaluating operational parameters of the careHPV, GeneXpert, AmpFire, and MA-6000 HPV systems for cervical precancer screening: Experience from Battor, Ghana.

In response to calls by the World Health Organization for cervical precancer screening services in low-resource settings to lean toward HPV DNA testing, a number of testing platforms have been made available. This study aimed to evaluate the operational parameters of four HPV testing systems in previous (careHPV) and current (GeneXpert, AmpFire, and MA-6000) use in a secondary healthcare setting in terms of 'appropriateness', ease of use, throughput, and diagnostic yield. This descriptive retrospective cohort analysis included 6056 women who presented to our facility between June 2016 and March 2022 for cervical precancer screening via HPV testing. A large majority of this cohort underwent AmpFire testing (55.8%), followed by careHPV (23.3%), MA-6000 (14.7%), and GeneXpert (6.1%). MA-6000 showed the highest hr-HPV positivity rate of 26.4% (95% CI, 23.6-29.5), followed by AmpFire (17.2%; 95% CI, 15.9-17.5). GeneXpert and careHPV showed similar hr-HPV positivity rates of 14.8% (95% CI, 11.3-18.8) and 14.8% (95% CI, 13.0-16.8), respectively. For the AmpFire and MA-6000 platforms, which utilize similar detection and reporting formats, we found a significant excess detection rate of 9.2% (95% CI, 6.1-12.4; p-value <0.0001) for MA-6000 compared to AmpFire. At the genotype level, MA-6000 also detected significantly higher rates of HPV 16 and other hr-HPV types (both p-values <0.001) than AmpFire; there was no difference in detection for HPV 18. Based on our experiences and preliminary analysis, we believe that the choice of HPV testing platform cannot be accomplished with a one-size-fits-all approach. Factors worth considering are the financial implications of platform acquisition, costs to clients, and throughput when screening programs are not sufficiently large. We describe our successes and challenges with the different platforms which we believe will be helpful to centers in low-income countries as they transition into using HPV DNA testing for cervical precancer screening.

Concurrent HPV DNA testing and a visual inspection method for cervical precancer screening: A practical approach from Battor, Ghana.

Cytology-based cervical cancer screening programs have been difficult to implement and scale up in developing countries. Thus, the World Health Organization recommends a 'see and treat' approach by way of hr-HPV testing and visual inspection. We aimed to evaluate concurrent HPV DNA testing and visual inspection in a real-world low-resource setting by comparing the detection rates of concurrent visual inspection with dilute acetic acid (VIA) or mobile colposcopy and hr-HPV DNA testing to standalone hr-HPV DNA testing (using the careHPV, GeneXpert, AmpFire, or MA-6000 platforms). We further compared their rates of loss to follow-up. This retrospective, descriptive cross-sectional study included all 4482 women subjected to cervical precancer screening at our facility between June 2016 and March 2022. The rates of EVA and VIA 'positivity' were 8.6% (95% CI, 6.7-10.6) and 2.1 (95% CI, 1.6-2.5), respectively, while the hr-HPV-positivity rate was 17.9% (95% CI, 16.7-19.0). Overall, 51 women in the entire cohort tested positive on both hr-HPV DNA testing and visual inspection (1.1%; 95% CI, 0.9-1.5), whereas a large majority of the women tested negative (3588/4482, 80.1%) for both and 2.1% (95% CI, 1.7-2.6) tested hr-HPV-negative but visual inspection 'positive'. In total, 191/275 (69.5%) participants who tested hr-HPV positive on any platform, as a standalone test for screening, returned for at least one follow-up visit. In light of factors such as poor socioeconomic circumstances, additional transportation costs associated with multiple screening visits, and lack of a reliable address system in many parts of Ghana, we posit that standalone HPV DNA testing with recall of hr-HPV positives will be tedious for a national cervical cancer prevention program. Our preliminary data show that concurrent testing (hr-HPV DNA testing alongside visual inspection by way of VIA or mobile colposcopy) may be more cost-effective than recalling hr-HPV-positive women for colposcopy.

Comparison of the AmpFire and MA-6000 polymerase chain reaction platforms for high-risk human papillomavirus testing in cervical precancer screening.

High-risk human papillomavirus (hr-HPV) testing for primary cervical precancer screening offers an opportunity to improve screening in low-middle income countries (LMICs). This study aimed to compare the analytic performances of the AmpFire and MA-6000 platforms for hr-HPV DNA testing in three groups of women screened for hr-HPV types in Ghana: group 1 with 33 GeneXpert-archived ThinPrep/liquid-based samples subjected to both tests, group 2 with 50 AmpFire-archived dry brush samples subjected to MA-6000 testing, and group 3 involving 143 cotton swab samples simultaneously subjected to both tests without archiving. The overall agreement rates were 73 %, 92 %, and 84 %, for groups 1-3, respectively, and 84 % (95 % CI, 78.6-88.6) for the entire group. Neither AmpFire nor MA-6000 was more likely to test hr-HPV positive in all three groups and the combined group. Group 1 showed fair agreement without statistical significance (κ = 0.224, 95 % CI, -0.118 to 0.565), while group 3 showed significant moderate agreement (κ = 0.591, 95% CI, 0.442-0.741). Group 2 showed an almost perfect significant level of agreement (κ = 0.802; 95 % CI, 0.616-0.987). Thus, both platforms showed statistically significant moderate to near-perfect agreement for detecting hr-HPV in cervicovaginal samples, with variation according to archiving conditions and duration between sample collection and retesting. For LMICs using these platforms for COVID-19 testing, as the COVID-19 pandemic subsides, the platforms can become available for running other tests such as hr-HPV DNA testing for cervical precancer screening.

A revolution in cervical cancer prevention in Ghana.

Though cervical cancer is largely preventable, success depends on sustained screening and treatment of precancer. This is not available in many low resource settings where screening and treatment services are not available due to a lack of government support. Our vision of setting up a comprehensive cervical cancer prevention scheme across Ghana that offers services tailored to fit every patient's needs, and relies on task shifting has been made possible through the setting up of the Cervical Cancer Prevention and Training Centre (CCPTC) to train and equip middle cadre staff (mostly nurses and midwives) to provide crucial cervical precancer screening and treatment services in many areas of the country that have never seen any such screening activities. To achieve this vision, we have learnt to produce crucial context relevant teaching materials and consumables locally, while adapting simple, readily available social media applications to raise crowd funds to support our work, use these apps to support routine work and to create a network of service providers at various service levels that can rely on each other and assure quality. Our vision has been supported by individuals and organizations that believe in it. They have allowed us to determine our growth and success. By sharing the experiences of the CCPTC we hope to encourage others to set up screening centers in low resource settings.

Application of the hub and spokes model in improving access to cervical cancer screening in Ghana.

Objective: To examine the contribution of lower-level health facilities in increasing access to cervical cancer screening in the North Tongu District. Design: A descriptive cross-sectional study design was used. The Cervical Cancer Prevention and Training Centre (CCPTC) of the Catholic Hospital, Battor, served as the hub, and six health facilities (3 health centres and 3 CHPS compounds) served as the spokes. From April 2018 to September 2019, the well-resourced CCPTC trained 6 nurses at selected Community-based Health Planning and Services (CHPS) / Health Centres (HCs) (spokes) to provide cervical cancer screening services. The nurses, after training, started screening with VIA and HPV DNA testing. Participants: A total of 3,451women were screened by the trained nurses. This comprised 1,935 (56.1%) from the hub and 1,516 (43.9%) from the spokes. Main outcome measure: The detection of screen positives. Results: The screen positives were 19.4% (375/1935) at the hub and 4.9% (74/1516) at the spokes. Conclusion: We have demonstrated that a hub and spokes model for cervical cancer screening is possible in limited resource settings. Designating and resourcing a 'hub' that supports a network of 'spokes' could increase women's access to cervical cancer screening. This approach could create awareness about cervical cancer screening services and how they can be accessed. Funding: None declared.

Application of the hub and spokes model in improving access to cervical cancer screening in Ghana

Objective: To examine the contribution of lower-level health facilities in increasing access to cervical cancer screening in the North Tongu District. Design: A descriptive cross-sectional study design was used. The Cervical Cancer Prevention and Training Centre (CCPTC) of the Catholic Hospital, Battor, served as the hub, and six health facilities (3 health centres and 3 CHPS compounds) served as the spokes. From April 2018 to September 2019, the well-resourced CCPTC trained 6 nurses at selected Community-based Health Planning and Services (CHPS) / Health Centres (HCs) (spokes) to provide cervical cancer screening services. The nurses, after training, started screening with VIA and HPV DNA testing. Participants: A total of 3,451women were screened by the trained nurses. This comprised 1,935 (56.1%) from the hub and 1,516 (43.9%) from the spokes. Main outcome measure: The detection of screen positives Results: The screen positives were 19.4% (375/1935) at the hub and 4.9% (74/1516) at the spokes. Conclusion: We have demonstrated that a hub and spokes model for cervical cancer screening is possible in limited resource settings. Designating and resourcing a 'hub' that supports a network of 'spokes' could increase women's access to cervical cancer screening. This approach could create awareness about cervical cancer screening services and how they can be accessed

Determining the prevalence of high-risk human papillomavirus infection using a novel cervical precancer screening approach in incarcerated women at the Nsawam Medium Security Prison, Ghana.

BACKGROUND: Across Ghana, females comprise 1.2% of the entire prison population (n = 15,463). Cervical cancer screening services are however nonexistent and the prevalence of high-risk human papillomavirus (hr-HPV) and cervical precancer is undocumented. We aimed to screen and treat inmates for cervical precancer and determine the prevalence of hr-HPV using the novel AmpFire HPV detection system combined with colposcopy by trained nurses using a mobile colposcope (the Enhanced Visual Assessment (EVA) system). METHODS: A descriptive cross-sectional study design was employed, involving all incarcerated women at the Nsawam Medium Security Prison, Ghana. After counselling and informed consent, women underwent a structured questionnaire-based interview entered into a Microsoft Excel spreadsheet. Women were co-tested for cervical pre-cancer and hr-HPV by two trained nurses using dry brush cervical samples for 15 hr-HPV types (AmpFire HPV test) after which mobile colposcopy with the EVA system was performed. EVA images were reviewed by a gynaecologist. Frequencies and percentages were used to describe categorical data, while means, standard deviations, medians and interquartile ranges (IQRs) were used to describe continuous data. RESULTS: 75% of the women were convicts with a median sentence of 5 years (IQR: 2-10 years). Their mean age was 41.1 years (standard deviation: 15.5 years, range: 19-97 years). The self-reported prevalence rate of HIV was 13.1% (95% confidence interval (CI): 7.5%-21.9%), all of whom were receiving treatment. The hr-HPV prevalence rate was 47.6% (CI: 36.9%-58.3%) in the general population of imprisoned women and 63.6% (CI: 35.4%-84.8%) among HIV positive women. Six percent (6%) had lesions on the cervix, of which 3.6% were treated with thermal coagulation and 2.4% were treated with loop electrosurgical excision procedure. The average age of hr-HPV positive women was 37.8 years. CONCLUSIONS: There is a high prevalence of hr-HPV infection among women in custody at the Nsawam Medium Security Prison. These women will benefit from structured cervical cancer prevention services, including treatment for abnormalities that are picked up during such screening.

Characterization of Human Papillomavirus prevalence and risk factors to guide cervical cancer screening in the North Tongu District, Ghana.

INTRODUCTION: This population-based study aimed to fill the knowledge gap on Human Papillomavirus (HPV) prevalence and associated sociodemographic risk factors of the general population in the North Tongu District, Ghana. These results are needed to guide cervical cancer prevention efforts, as the leading type of female cancers. METHODS: A cross-sectional study including 2002 women in the North Tongu District, Ghana investigated HPV prevalence and associated sociodemographic risk factors. Women were recruited by geographical distribution through the local community-based health system and samples collected using a self-sampling device. For HPV genotyping BSGP5+/6+-PCR with Luminex-MPG readout was used. Multivariate logistic regression analyzed sociodemographic risk factors for HPV positivity. RESULTS: Of 2002 self-collected samples, 1943 were eligible, contained sufficient DNA and provided valid HPV genotyping results. Prevalence of single high risk HPV types was 32.3% and of multiple high risk types 9.7%. The five most common detected HPV types were HPV16 (7.4%; 95%CI: 6.3-8.7), HPV52 (7.2%; 95%CI: 6.1-8.5), HPV35 (4.8%; 95%CI: 3.9-5.8), HPV59 (4.7%; 95%CI: 3.8-5.8), HPV56 (3.9%; 95%CI: 3.1-4.8). Highest prevalence was observed among women aged 18-24 years, while age 25-54 years was inversely associated with high risk HPV positivity in multivariate analysis. Sociodemographic risk factors identified were i) having any sexual partner, ii) more partners increased the odds for high risk HPV positivity, iii) independently from this marital status, in particular not being married. DISCUSSION & CONCLUSION: Most importantly, the high risk HPV prevalence detected from this study is higher than estimates reported for Western Africa. This needs be considered, when deciding on the cervical cancer screening algorithms introduced on a wider scale. Follow-up and triage, depending on the methods chosen, can easily overburden the health system. Self-sampling worked well and provided adequate samples for HPV-based screening. Women with increasing number of sexual partners and not being married were found to have higher odds of being high risk HPV positive, therefore could be a higher prioritized screening target group.

Dynamics of genotype-specific HPV clearance and reinfection in rural Ghana may compromise HPV screening approaches.

Persistent Human Papillomavirus (HPV) infection is a prerequisite for cervical cancer development. Few studies investigated clearance of high-risk HPV in low-and-middle-income countries. Our study investigated HPV clearance and persistence over four years in women from North Tongu District, Ghana. In 2010/2011, cervical swabs of 500 patients were collected and HPV genotyped (nested multiplex PCR) in Accra, Ghana. In 2014, 104 women who previously tested positive for high-risk HPV and remained untreated were re-tested for HPV. Cytobrush samples were genotyped (GP5+/6+ PCR & Luminex-MPG readout) in Berlin, Germany. Positively tested patients underwent colposcopy and treatment if indicated. Of 104 women, who tested high-risk HPV+ in 2010/2011, seven (6,7%; 95%CI: 2.7-13.4%) had ≥1 persistent high-risk-infection after ~4 years (mean age 39 years). Ninety-seven (93,3%; 95%CI: 86.6-97.3%) had cleared the original infection, while 22 (21.2%; 95%CI: 13.8-30.3%) had acquired new high-risk infections with other genotypes. Persistent types found were HPV 16, 18, 35, 39, 51, 52, 58, and 68. Among those patients, one case of CIN2 (HPV 68) and one micro-invasive cervical cancer (HPV 16) were detected. This longitudinal observational data suggest that single HPV screening rounds may lead to over-referral. Including type-specific HPV re-testing or additional triage methods could help reduce follow-up rates.