TEST:

Xpert HPV Assay

hr-HPV infection and cervical abnormalities are common among WLHIV starting ART, especially those with low CD4 counts, highlighting that early HIV testing and treatment initiation must be prioritised together with cervical cancer screening. The diversity of hr-HPV types suggests a need for vaccines with expanded HPV type coverage in this setting.

Enrolled were 1104 women, mean age 41.3 years, 58.7% were HNW. The sensitivity/specificity/PPV/NPV of the different tests to detect CIN3+ in HNW were: Onclarity® 63.8%/82.3%/38.1%/94.7%; HC2 59.2%/83.8%/27.9%/95.1%; Roche cobas® 68.2%/81.6%/29.6%/95.8%; GeneXpert 64.1%/85.1%/33.6%/95.3%; Aptima 36.2%/90.0%/29.2%/92.5% and PreTect-Proofer-8 24.4%/87.6%/13.7%/93.5%. In HPW, respective sensitivity/specificity/PPV/NPV to detect CIN3+ were: Onclarity 80.8%/67.5%/44.7%/91.6%; HC2 77.1%/63.0%/36.0%/91.1%; Roche cobas® 82.1%/61.7%/39.4%/91.9%; GeneXpert 80.2%/64.4%/40.7%/91.4%; Aptima 42.2%/77.0%/36.8%/80.8% and PreTect-Proofer-8 46.4%/66.4%/28.5%/81.1%.

Our research confirms a widespread HR-HPV infection in our population and extends the importance of studies on the molecular prevalence of HPV, particularly in women with normal cytology and apparent good health, in view of the cruel lack of public awareness of HPV infections.

In this study of stored specimens, the ScreenFire HPV assay performed well in the detection of HPV and CIN2+ among WLWH compared to the Xpert HPV assay. If supported by larger validation studies, ScreenFire could be an affordable alternative point-of-care HPV assay for use in LMICs.

Ongoing investigations include evaluating SteriPack nylon flocked swabs in a clinical trial comparing healthcare provider-collected vs self-collected swab specimens for hrHPV detection. In summary, our research showcases advancements in hrHPV near point-of-care assays, coupled with cost-effective swabs, representing a significant stride forward for hrHPV diagnostics in LMICs.

Prevalence of hr-HPV among WLHIV was high compared to that reported for HIV negative women, suggesting that hr-HPV screening may be helpful as part of routine care for WLHIV, especially for women below the age of 45 years, women with younger age at sexual debut, and those with STI symptoms during clinic visits.

A multi-step screening algorithm utilizing HPV self-testing, VIA triage and thermal ablation treatment requires proper counseling and anticipatory guidance to improve patient understanding. Incorporating thorough counseling in CxCa screening programs can change women's perspectives about screening, build trust in healthcare systems, and influence healthcare seeking behavior towards routine screening and prevention.

The results suggest that the percentage of association between samples with abnormal cervical presentation and negative high-risk HPV diagnosis is noticeably increasing. This underscores the need for effective screening programs and an understanding of the impact of specific HPV genotypes on cervical abnormalities.

In Benin, anal HR-HPV was common among HIV-negative men who have sex with men. Among this highly vulnerable population, there is a need for integrated preventive and management strategies targeting HPV and other sexually transmitted infections.

Of the 9,014 women enrolled, 2,805 (31.1%) tested positive for at least one HR-HPV type: HPV16 (n=477, 17%), HPV18/45 (n=688, 24.5%) and non-16/18/45 (2,157, 76.9%). 23.2% of participants with HR-HPV had multiple types present. HR-HPV infection was more frequently observed among women living with HIV (WLWH) compared with HIV-negative women (39.5% vs, 24.2% respectively; p<0.001), with non-16/18/45 also being the most frequent type in this population (69.6%).

SAT programs need to weigh trade-offs between overtreatment versus delayed or no treatment for women who test positive for HPV. Treatment modalities for precancerous lesions need to be improved.

P=N/A; N=1000; Recruiting; Sponsor:Weill Medical College of Cornell University

Among women, high-risk HPV prevalence was low. However, the knowledge on epidemiology of HPV infection in this population should be improved

Urine-based Xpert® HPV test seems to be a suitable screening test for detection of HR-HPV infections associated with low- and high-grade lesions requiring follow-up monitoring or treatment. This methodology, relying on noninvasively collected samples and on available rapid testing platforms, could facilitate large, at-scale screening programs, particularly in LMICs and rural areas, thus reducing adverse outcomes of HPV infection and facilitating achievement of the WHO cervical cancer elimination goal.

The AmpFire HPV assay demonstrated excellent analytic performance in both detection of HPV and clinically significant cervical disease. AmpFire HPV is a promising option to increase access to affordable, type-specific HPV screening for cervical cancer in LMICs.

The magnitude of hr-HPV is still high compared to the global prevalence. HIV-positive women and those in multiple sexual relationships should be prioritized in cervical cancer screening programs. The presence of abnormal vaginal discharge in gynecology clinics should prompt HPV testing.

In the studied regions, HPV types 16,31,33,35,52 were most often detected, which should be taken into account when developing the country's national screening program. Also, given the age-specific prevalence of HPV, may be considered for the target group of cervical cancer screening of women aged 35 and 45 years, which is more acceptable for a developing country.

Presently, Xpert HPV appears to have limited use for oral HPV detection among PLHIV using oral samples. More research to improve the diagnostic capabilities of Xpert HPV for oral samples among PLHIV is needed.

In this study among Kenyan WLHIV, integrating Xpert HPV into HIV care was feasible with high uptake and prevalence of HR-HPV. WLHIV with HR-HPV almost universally completed referrals for VIA/VILLI which frequently detected cervical abnormalities. Xpert HPV could potentially enhance cervical cancer screening programs for WLHIV in high-burden settings.

Finally, a formal usability assessment was conducted with users in El Salvador and Mozambique; the assay was rated as acceptable to perform after minimal training. With additional optimization for higher cell concentrations and inclusion of an internal cellular control, the paper HPV DNA assay offers promise as a low-cost, point-of-care cervical cancer screening test in low-resource settings.

Overall, there was good to excellent agreement between the Xpert and AmpFire when testing hrHPV types among women living with HIV. AmpFire was more likely to test extra cases of HPV16, the most carcinogenic HPV type, but the clinical meaning of detecting additional HPV16 infections remains unknown.

Extended genotyping identified women who tested positive in the first 3 channels to be at highest risk for CIN2+. These women could be directly referred for treatment. Women testing positive for channels 4 and 5 should either be subjected to a second triage test or followed up.

P=N/A; Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Jul 2022 --> Jul 2023

Copan MSwab is a transport and preservation medium that can be used to test the eluted vaginal sample up to 96 hours after elution even if stored at extreme temperatures. Copan MSwab can be considered a useful substitute to expensive and difficult to handle alcohol-based media even in extreme settings, such as remote regions that are difficult to reach and where it is not always possible to maintain controlled temperatures and refrigeration.

Copan MSwab® is a optimal transport and elution media for HPV detection. In this study, we show that Copan MSwab® can maintain HPV nucleic acid integrity for long storage time in dry collection, wet collection and even when the sample is stocked dry for a long time and tested with a delay post-elution. Thanks to these properties, Copan MSwab® allows laboratory flow flexibility, adapting to different real-world testing needs from the small point of care settings to the big, automated laboratory pipelines.

Visual inspection after a positive HPV result is a good triage option with high sensitivity to identify women needing treatment even if inter-sites heterogeneity suggests differences in practice. While partial genotyping showed insufficient sensitivity, an algorithm combining partial genotyping and VIA/VILI appears to be the most efficient.

We will evaluate same-day completion of our algorithm, its performance in triaging women for treatment, and 24-week treatment efficacy of thermal ablation. We will also explore the performance of HPV and methylation tests in urine samples, as compared to provider- and self-collected cervicovaginal samples.

"Analysis of the valid results from our data indicates that L1 and E6/E7 targeting assays show similar performance for detection of hrHPV in high grade cervical lesions and cancers of cervix, penis and oropharynx."

A screening approach using HPV testing alone can be more easily implemented at the point-of-care.

The predominance of HPV-16 and HPV-18/45 genotypes in the study setting is a consideration that would benefit targeted prophylactic vaccination programs. HPV testing and cervical cancer screening for young and older women on a regular basis ought to be reinforced.

Xpert HPV is an alternative to anal cytology to screen for anal HSIL and can be optimized to reduce the number of unnecessary HRAs performed in WLWH.

Eleven hrHPV DNA assays fulfil all requirements for use in cervical cancer screening using clinician-collected specimens.

"The Xpert test has a high sensitivity for detecting the recurrence of cancer and a high negative predictive value for excluding HG cancer. In addition, the data suggest that patients with a positive Xpert assay in setting of negative cystoscopy are at high risk for recurrence and need close surveillance."

"The self-collected sample had good agreement with the clinician-collected sample for the detection of HPV, and restricting the HPV types may improve the specificity in HIV-positive women."