Expanding management strategies for cervical precancerous lesions in resource-limited settings: insights from a training center in a district hospital in Ghana.

BACKGROUND: Cervical cancer continues to disproportionately burden women in low/middle-income countries like Ghana. We examined treatment patterns and histopathological outcomes among women screened using visual inspection with acetic acid (VIA) and/or mobile colposcopy who subsequently underwent thermal ablation, large loop excision of the transformation zone (LLETZ), or cold knife conization at the Cervical Cancer Prevention and Training Centre, Battor. We also assessed the prevalence of cervical intraepithelial neoplasia 2+ (CIN2+) or micro-invasive disease and their associated factors for women who underwent excisional treatments. The treatment choices for cervical precancerous lesions suitable for resource-limited settings have also been described from the perspective of a center that manages a heterogenous population. METHODS: We conducted an analysis of secondary data collected between June 2016 and June 2023 among women with positive findings on VIA or mobile colposcopy who subsequently underwent thermal ablation or large loop excision of the transformation zone (LLETZ). The prevalence of histopathology outcomes, including no dysplasia, CIN1 - 3, and micro-invasive disease, were estimated with 95% confidence intervals (CIs). Factors associated with histopathological findings were modeled using multinomial logistic regression. RESULTS: For the study period, 14 (10.6%) of the total 132 participants underwent cervical lesion treatment at outreach locations, all via thermal ablation. The remaining 118 (89.4%) were treated at the Catholic Hospital, Battor using LLETZ (n = 66, 55.9%), thermal ablation (n = 51, 43.2%), and cold knife conization (n = 1, 0.9%). Among 65 women with histopathology reports, the most frequent histopathological finding was no dysplasia (47.7%; 95% CI, 35.1 - 60.5), followed by CIN2 and CIN3 (20.0%; 95% CI, 11.1 - 31.8 each), CIN1 (7.7%; 95% CI, 2.5 - 17.0) and micro-invasion (4.6%; 95% CI, 1.0 - 12.9). Those with micro-invasive disease were significantly older than those with CIN1, CIN2, and CIN3 (p = 0.036, 0.022, 0.009, respectively), but not significantly older than those who showed no dysplasia (p = 0.088). For each unit increase in age, the likelihood of CIN3 was relatively significantly reduced compared to no dysplasia (crude relative risk ratio [RRR] = 0.93; 95% CI, 0.86 - 0.99). This association was neither observed with the remaining histopathological groups nor for parity and persisted after controlling for parity (adjusted RRR = 0.92; 95% CI, 0.85 - 0.99; p = 0.025). CONCLUSION: This paper largely demonstrates treatment options available to women and practitioners in LMICs. The high combined prevalence of high-grade precancerous lesions and micro-invasive disease underscores the need to increase cervical cancer awareness that would enhance screening attendance and hasten efforts at moving from opportunistic to organized screening in Ghana. This will enhance early cervical lesion detection and treatment, while simultaneously re-evaluating and cutting down on unnecessary treatment.

Quality assurance in cytology reporting in Ghana: an urgent call.

Introduction: In Ghana, the Papanicolaou (PAP) smear remains central to cervical cancer screening although human papilloma virus testing is recommended. The success of the PAP smear however depends on stringent quality processes. Unfortunately, PAP smear reporting in Ghana is uncoordinated with no clear quality guidelines. Methods: We applied quality guidelines to all PAP smear diagnoses of high-grade squamous intraepithelial lesion (HSIL) at Catholic Hospital Battor from 1 June 2016 to 31 August 2021. Available slides were independently reviewed by two pathologists, colposcopy findings were correlated with PAP smear results and histology cytology correlation was carried out after loop electrosurgical excision procedure (LEEP). Results: Of 17 women with HSIL, 3 available slides were reviewed and found to be normal (negative for intraepithelial lesion or malignancy), obviating the need for LEEP. Of the 11 that had LEEP after colposcopy, cytology histology correlation revealed that 54.6% (6) had no dysplasia, 27.3% (3) were cervical intraepithelial neoplasia (CIN) II and 18.2% (2) were CIN III. Cytology, colposcopy correlation showed that (out) of the 17 women, 52.9% (9) had no lesions, 29.4% (5) had minor changes and 17.7% (3) had major changes on their cervix. Of the nine that had no lesions on colposcopy, five had LEEP. Of these five, dysplasia (at least CIN II) was revealed in three (60%). Conclusion: The lack of quality processes in PAP smear reporting results in a high false positive rate with overtreatment of patients. Quality measures need to be adopted for the reporting of PAP smears in Ghana if gains are to be made in the fight against cervical cancer.

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.

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.

Antenatal and postnatal cervical precancer screening to increase coverage: experience from Battor, Ghana.

Background: Cervical precancer screening in low-resource settings is largely opportunistic with low coverage. Many women in these settings, where the burden of cervical cancer is highest, only visit health institutions when pregnant or after delivery. We explored screening during antenatal and postnatal visits aimed at increasing coverage. Methods: Pregnant women (in any trimester) attending antenatal care (ANC) and women attending postnatal care (PNC; 6-10 weeks) clinics were screened at Catholic Hospital, Battor and at outreach clinics from February to August 2022 (08/02/2022 to 02/08/2022). At the same visit, cervical specimens were obtained for high-risk human papillomavirus (hr-HPV) DNA testing (with the Sansure MA-6000 PCR platform) followed by either visual inspection with acetic acid (VIA) or mobile colposcopy with the enhanced visual assessment system. Results: Two hundred and seventy and 107 women were screened in the antenatal and postnatal groups, respectively. The mean ages were 29.4 (SD, 5.4) in the ANC group and 28.6 (SD, 6.4) years in the PNC group. The overall hr-HPV prevalence rate was 25.5% (95% confidence interval (CI), 21.1-29.9) disaggregated as 26.7% (95% CI, 21.4-31.9) in the ANC group and 22.4% (95% CI, 14.5-30.3) in the PNC group (p = 0.3946). Overall, 58.9% of pregnant women (28.3% hr-HPV+) and 66.4% of postnatal women (22.5% hr-HPV+) only visited a health facility when pregnant or after delivery (at Child Welfare Clinics). The VIA 'positivity' rate for all screened women was 5.3% (95% CI, 3.1-7.6), disaggregated into 5.2% (95% CI, 2.5-7.8) in the ANC group and 5.7% (95% CI, 1.3-10.1) in the PNC group (p-value = 0.853). Conclusion: A significant number of women in Ghana only visit a health facility during pregnancy or after delivery. ANC and PNC clinics would offer opportunities to increase coverage in cervical precancer screening in low-resource settings. Relying on community nurses ensures that such programs are readily integrated into routine care of women and no opportunity is missed.

Tritesting in Battor, Ghana: an integrated cervical precancer screening strategy to mitigate the challenges of multiple screening visits and loss to follow-up.

Background: Human papillomavirus (HPV) DNA testing is more sensitive than cytology for detecting cervical precancer; however, increasing reports of high-risk HPV (hr-HPV)-negative cases of cervical intraepithelial neoplasia (CIN) and even malignancy motivate the use of combined testing. We present our experience with 'tritesting', defined as the performance of HPV DNA testing, cytology and visual inspection in a single session at the Cervical Cancer Prevention and Training Centre, Ghana. We further determined the prevalence rates of hr-HPV infection, abnormal cytology and cervical lesions among women screened using tritesting. Methods: This descriptive retrospective cross-sectional study assessed all women screened via tritesting between April 2019 to April 2023. HPV DNA testing was performed using the Sansure MA-6000, GeneXpert or AmpFire platforms. Visual inspection was performed using enhanced visual assessment mobile colposcopy or visual inspection with acetic acid. Liquid-based cytology was performed using cervical samples taken with a Cervex-Brush® and fixed in PreservCyt, while samples for conventional cytology were taken using an Ayre spatula and cytobrush. Results: Among 236 women screened (mean age, 39.1 years (standard deviation, 10.9)), the overall prevalence rates of hr-HPV infection and cervical lesions were 17.8% (95% confidence interval (CI), 13.1-23.3) and 11.9% (95% CI, 8.0-16.7), respectively. Cytology yielded findings of atypical squamous cells of undetermined significance or worse in 2.5% (95% CI, 0.9-5.5) of women. Histopathology following loop electrosurgical excision procedure revealed CIN I (tritest positive) and CIN III (hr-HPV-positive, visual inspection 'positive', cytology-negative) in one woman each. Factors independently associated with hr-HPV infection among 'tritested' women were age ≥ 39 years, tertiary level of education and current contraceptive use. Twenty-seven out of 39 hr-HPV-positive women (69.2%; 95% CI, 52.4-83.0) showed a type 3 transformation zone and would have needed to be recalled for a cytologic sample to be taken in a 'see and triage' approach with HPV DNA testing and a visual inspection method. Conclusion: This study brings tritesting into the spotlight, as an alternative to other methods, particularly for women who prefer this due to the advantage of a single visit to a health facility and being more cost-effective, if they have to travel long distances to access cervical screening services.

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.

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.