Field experience with the 8-HPV-type oncoprotein test for cervical cancer screening among HPV-positive women living with and without HIV in LMICs.

Overexpression of HPV-oncoproteins E6 and E7 is necessary for HPV-driven cervical carcinogenesis. Hence, these oncoproteins are promising disease-specific biomarkers. We assessed the technical and operational characteristics of the 8-HPV-type OncoE6/E7 Cervical Test in different laboratories using cervical samples from HPV-positive women living with (WLWH) and without HIV. The 8-HPV-type OncoE6/E7 Test (for short: "OncoE6/E7 test") was performed in 2833 HIV-negative women and 241 WLWH attending multicentric studies in Latin America (ESTAMPA study), and in Africa (CESTA study). Oncoprotein positivity were evaluated at each testing site, according to HIV status as well as type-specific agreement with HPV-DNA results. A feedback questionnaire was given to the operators performing the oncoprotein test to evaluate their impression and acceptability regarding the test. The OncoE6/E7 test revealed a high positivity rate heterogeneity across all testing sites (I2: 95.8%, p < .01) with significant lower positivity in WLWH compared to HIV-negative women (12% vs 25%, p < .01). A similar HPV-type distribution was found between HPV DNA genotyping and oncoprotein testing except for HPV31 and 33 (moderate agreement, k = 0.57). Twenty-one laboratory technicians were trained on oncoprotein testing. Despite operators' concerns about the time-consuming procedure and perceived need for moderate laboratory experience, they reported the OncoE6/E7 test as easy to perform and user-friendly for deployment in resource-limited settings. The high positivity rate variability found across studies and subjectivity in test outcome interpretation could potentially results in oncoprotein false positive/negative, and thus the need for further refinements before implementation of the oncoprotein testing in screen-triage-and-treat approaches is warranted.

Cervical Cancer Screening and Treatment algorithms using Human Papillomavirus testing - lessons learnt from a South African pilot randomized controlled trial.

BACKGROUND: To report quantitative and qualitative results on cervical cancer (CC) HPV-based screening and treatment algorithms, with/out triage with visual inspection after acetic acid (VIA), followed by ablative treatment (AT). METHODS: Women 30-54 years-old from Durban, South Africa were recruited, regardless of HIV status, randomized into one of two study arms and screened for HPV. VIA-triage arm: HPV-positive women were triaged using VIA, biopsied and received AT if VIA-positive and eligible; no-triage arm: eligible HPV-positive women received AT. Women ineligible for AT were referred to colposcopy. Women were asked about side effects immediately and one week after AT. Retention to screening and treatment algorithms was compared between arms. RESULTS: 350 women (275 HIV-uninfected and 75 women living with HIV, (WLWH)) were allocated to receive HPV testing with VIA-triage (n=175) or no-triage (n=175). HPV prevalence was 28% (95%CI=23-33); WLWH: 52% (95%CI=40-64) vs HIV-uninfected: 21% (95%CI=17-27) (p<0.05). Among women who underwent VIA triage with histological diagnosis, 3/17 were VIA negative with CIN2+; 14/18 were VIA positive with

Cervical cancer screening by visual inspection and HPV testing in Eswatini.

In 2009, visual inspection with acetic acid (VIA) followed by cryotherapy (VIA-and-cryotherapy), was introduced into the Eswatini cervical cancer prevention programme. We present screening results of 654 women attending VIA-and-cryotherapy who participated in a sexually transmitted infections prevalence study, at which samples for HPV DNA testing and liquid-based cytology (LBC) were also collected. VIA positives (VIA+) ineligible for cryotherapy, suspected cancers and women with high-grade squamous intraepithelial or worse lesions (HSIL+) on LBC were referred for diagnosis and treatment. Women with negative VIA who were HPV positive (HPV+) and those VIA+ treated with cryotherapy were recalled for another VIA one-year later. The positivity rates of VIA, HPV, atypical squamous cells of undetermined significance or worse cytology abnormalities (LBC ASCUS+) and low-grade squamous intraepithelial or worse lesions (LBC LSIL+) were 9.7%, 42.6%, 13.2% and 5.3%, respectively. HPV testing detected 29 of 31 LSIL+ (93.6%, 95%CI: 78.6-99.2) while VIA only detected 11 (35.6%, 95%CI: 19.2-54.6). The HIV prevalence was 43% (95%CI: 39.2-46.9). HIV positives were at increased risk of being VIA+ (age-adjusted odds ratio: 2.5, 95%CI: 1.5-4.3), HPV+ (3.7, 2.6-5.3) and having LSIL+ (16.3, 4.9-54.8). The ineligibility rates for cryotherapy were 38% (24 of 63 VIA+), and 46% among HIV positives (18 of 39 VIA+). HPV testing was substantially more sensitive than VIA, thus, HPV followed by ablative treatment may be more effective. However, the high ineligibility for cryotherapy highlights the need for improving the assessment of eligibility for ablative treatment and for strengthening colposcopy, particularly in populations with high HIV prevalence.