Addition of digital VIA/VILI to conventional naked-eye examination for triage of HPV-positive women: A study conducted in a low-resource setting.

BACKGROUND: World Health Organization guidelines for cervical cancer screening recommend HPV testing followed by visual inspection with acetic acid (VIA) for triage if HPV positive. In order to improve visual assessment and identification of cervical intraepithelial neoplasia grade 2 and worse (CIN2+), providers may use visual aids such as digital cameras. OBJECTIVES: To determine whether combined examination by naked-eye and digital VIA (D-VIA) and VILI (D-VILI) improves detection of CIN2+ as compared to the conventional evaluation. MATERIALS AND METHODS: Women (30-49 years) living in Dschang (West Cameroon) were prospectively invited to a cervical cancer screening campaign. Primary HPV-based screening was followed by VIA/VILI and D-VIA/VILI if HPV-positive. Health care providers independently defined diagnosis (pathological or non-pathological) based on naked-eye VIA/VILI and D-VIA/VILI. Decision to treat was based on combined examination (VIA/VILI and D-VIA/VILI). Cervical biopsy and endocervical curettage were performed in all HPV-positive participants and considered as reference standard. Diagnostic performance of individual and combined naked-eye VIA/VILI and D-VIA/VILI was evaluated. A sample size of 1,500 women was calculated assuming a prevalence of 20% HPV positivity and 10% CIN2+ in HPV-positive women. RESULTS: Due to the COVID-19 pandemic, the study had to terminate prematurely. A total of 1,081 women with a median age of 40 (IQR 35.5-45) were recruited. HPV positivity was 17.4% (n = 188) and 26 (14.4%) had CIN2+. Naked-eye VIA and D-VIA sensitivities were 80.8% (95% CI 60.6-93.4) and 92.0% (95% CI 74.0-99.0), and specificities were 31.2% (95% CI 24-39.1) and 31.6% (95% CI 24.4-39.6), respectively. The combination of both methods yielded a sensitivity of 92.3% (95% CI 74.9-99.1) and specificity of 23.2% (95% CI 16.8-30.7). A trend towards improved sensitivity was observed, but did not reach statistical significance. CONCLUSION: Addition of D-VIA/VILI to conventional naked-eye examination may be associated with improved CIN2+ identification. Further studies including a larger sample size are needed to confirm these results.

Utility of extended HPV genotyping for the triage of self-sampled HPV-positive women in a screen-and-treat strategy for cervical cancer prevention in Cameroon: a prospective study of diagnostic accuracy.

OBJECTIVE: To explore the utility of extended Human Papillomavirus (HPV) genotyping to detect cervical intraepithelial neoplasia grade 2 or more (CIN2+) in a 'screen-and-treat' strategy for HPV-positive women in low-resource settings. DESIGN: Prospective study of diagnostic accuracy. SETTING: The study took place in West Cameroon between September 2018 and March 2020. PARTICIPANTS: 2014 women were recruited. Asymptomatic, non-pregnant women aged 30-49 years without history of CIN treatment, anogenital cancer or hysterectomy were eligible. INTERVENTIONS: Participants performed self-sampling for HPV testing with GeneXpert followed by visual inspection with acetic acid and Lugol's iodine (VIA) triage before treatment if required. MAIN OUTCOME MEASURES: Liquid-based cytology, biopsies and endocervical brushing were performed in HPV-positive women as quality control. We assessed the detection rate of CIN2+ by HPV genotyping (two pools of genotypes obtained from the Xpert system, pool_1 (HPV 16, 18, 45) and pool_2 (HPV 16, 18, 45, 31, 33, 35, 52, 58)), VIA and cytology. RESULTS: 382 (18.2%) women were HPV-positive among which 11.5% (n=44) were CIN2+. Of those 44 participants, 41 were triaged positive by extended genotyping, versus 35 by VIA and 33 by cytology. Overall, triage positivity was of 68.4% for extended genotyping, 59.3% for VIA and 14.8% for cytology, with false positive rates of 83.4%, 84.1% and 37.7%, respectively. Extended genotyping had a higher sensitivity for CIN2+ detection (93.2%, CI: 81.3 to 98.6) than VIA (79.5%, CI: 64.7 to 90.2, p=0.034) and cytology (75.0%, CI: 59.7 to 86.8, p=0.005). No significant difference was observed in the overtreatment rate in triaged women by extended genotyping or VIA (9.9%, CI: 8.6 to 11.3, and 8.8%, CI: 7.7 to 10.1), with a ratio of 6.0 and 6.3 women treated per CIN2+ diagnosed. CONCLUSION: Triage of HPV-positive women with extended HPV genotyping improves CIN2+ detection compared with VIA with a minor loss of specificity and could be used to optimize the management of HPV-positive women. TRIAL REGISTRATION NUMBER: NCT03757299.

Study protocol for a two-site clinical trial to validate a smartphone-based artificial intelligence classifier identifying cervical precancer and cancer in HPV-positive women in Cameroon.

INTRODUCTION: Cervical cancer remains a major public health challenge in low- and middle-income countries (LMICs) due to financial and logistical issues. WHO recommendation for cervical cancer screening in LMICs includes HPV testing as primary screening followed by visual inspection with acetic acid (VIA) and treatment. However, VIA is a subjective procedure dependent on the healthcare provider's experience. Its accuracy can be improved by computer-aided detection techniques. Our aim is to assess the performance of a smartphone-based Automated VIA Classifier (AVC) relying on Artificial Intelligence to discriminate precancerous and cancerous lesions from normal cervical tissue. METHODS: The AVC study will be nested in an ongoing cervical cancer screening program called "3T-study" (for Test, Triage and Treat), including HPV self-sampling followed by VIA triage and treatment if needed. After application of acetic acid on the cervix, precancerous and cancerous cells whiten more rapidly than non-cancerous ones and their whiteness persists stronger overtime. The AVC relies on this key feature to determine whether the cervix is suspect for precancer or cancer. In order to train and validate the AVC, 6000 women aged 30 to 49 years meeting the inclusion criteria will be recruited on a voluntary basis, with an estimated 100 CIN2+, calculated using a confidence level of 95% and an estimated sensitivity of 90% +/-7% precision on either side. Diagnostic test performance of AVC test and two current standard tests (VIA and cytology) used routinely for triage will be evaluated and compared. Histopathological examination will serve as reference standard. Participants' and providers' acceptability of the technology will also be assessed. The study protocol was registered under ClinicalTrials.gov (number NCT04859530). EXPECTED RESULTS: The study will determine whether AVC test can be an effective method for cervical cancer screening in LMICs.