Human papillomavirus mRNA testing for the detection of anal high‐grade squamous intraepithelial lesions in men who have sex with men infected with HIV

Abstract

Currently, screening for anal high-grade squamous intraepithelial lesions (anal HSIL) relies on anal cytology and high-resolution anoscopy. Since this approach has limited sensitivity and specificity for detecting anal HSIL, there is increasing interest in the role of biomarkers for predicting anal HSIL. The aim of this study is to evaluate the diagnostic accuracy of HPV E6/E7-mRNA expression for the detection of anal HSIL in MSM infected with HIV, in comparison to DNA-HR-HPV and anal cytology. This cross-sectional screening study included 101 MSM followed at the HIV-unit of La Paz University Hospital. Intra-anal swabs from patients participating in a screening program including cytology, high-resolution anoscopy and histology were analyzed. HR-HPV-DNA detection was performed by means of the CLART® HPV2 assay (GENOMICA S.A.U., Madrid, Spain). E6/E7-mRNA detection of HR-HPV-types 16, 18, 31, 33, and 45 was performed using the NucliSENS-EasyQ assay (BioMérieux, Marcy ĺEtoile, France). HR-HPV DNA and HPVE6/E7 mRNA were detected in 82% and 57% of the anal smears respectively. Anal cytology screening was abnormal in 70.3%. For the detection of HSIL sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 71.7%, 55.6%, 57.9%, and 69.8% for E6/E7-mRNA testing, respectively, compared to 100%, 31.5%, 55.4%, and 100% for HR-HPV-DNA testing and to 83%, 40.7%, 54.9%, 73.3% of cytology testing. In comparison with the other tests, HPVE6/E7 mRNA testing yielded a lower clinical sensitivity but a higher clinical specificity and PPV for the detection of anal HSIL in MSM infected with HIV.

Prevalence of Anal HPV and Anal Dysplasia in HIV-Infected Women From Johannesburg, South Africa

“…Other studies have found that the sensitivity of E6/E7 mRNA for cervical HSIL was similar to HR-HPV DNA assays. 31, 32 It is not clear why the sensitivity of E6/E7 mRNA for anal HSIL appeared lower in our study. Our estimated sensitivity was similar when considering HSIL on histology alone, HSIL on cytology or HSIL on either test (data not shown).…”

Strategies for screening and early detection of anal cancers: A narrative and systematic review and meta‐analysis of cytology, HPV testing, and other biomarkers

“…Four studies evaluated the performance of E6/E7 mRNA for the detection of anal precancer and cancer, including a mix of HIV‐positive and HIV‐negative MSM (Supporting Table 1) . The pooled sensitivity and specificity of E6/E7 mRNA was 74.3% (95% CI, 68.3%‐79.6%) and 65.5% (95% CI, 58.5%‐71.9%), respectively (Fig.…”

Histological outcomes of anal high‐grade cytopredictions

“…The observation that 12.6% of men with negative cytology at the baseline had a histological HSIL identified at that particular visit has been previously reported by our group . Others have reported false‐negative rates ranging from 11% to 81% . The high rate of histological HSILs in the anus with negative cytology may be related to the anatomical complexity of the anal canal, the size of the area sampled, and the blind sampling technique used in comparison with the sampling of the cervix under direct vision.…”

“…Several recent studies with a design similar to SPANC have reported performance characteristics of anal cytology, and these are presented in Table . None of these report changes in PPVs over time.…”

“…Knowledge of likely outcomes for each cytological report will enable the most appropriate management decisions to be made for each participant. Table compares PPVs in studies with a design similar to ours, in which cytology and histology are both performed at the same visit . SPANC is the largest such study to date and has longitudinal data (not included in the table), which may increase its relevance to clinical management decisions.…”