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. 2024 Dec 27;12(1):ofae735.
doi: 10.1093/ofid/ofae735. eCollection 2025 Jan.

Using Anal Cytology and Human Papillomavirus DNA and E6/E7 mRNA Detection to Optimize High-Resolution Anoscopy Referrals in Men Who Have Sex With Men With HIV

Ana C Silva-Klug  1 , Sònia Paytubi  2   3 , Montserrat Torres  2   3 , Loris Trenti  4 , Nuria Baixeras  5 , Monica Sanchez-Llamas  1 , Miquel A Pavon  2   3 , Silvia De Sanjose  6 , Isabel Catala  5 , August Vidal  5 , Mario Poljak  7 , Laia Alemany  2   3 , Daniel Podzamczer  1 , Sebastian Videla  8 , Maria Saumoy  1
Affiliations

Using Anal Cytology and Human Papillomavirus DNA and E6/E7 mRNA Detection to Optimize High-Resolution Anoscopy Referrals in Men Who Have Sex With Men With HIV

Ana C Silva-Klug et al. Open Forum Infect Dis. .

Abstract

Background: This study was conducted to evaluate screening procedures for anal high-grade squamous intraepithelial lesions (HSILs) with anal liquid-based cytology (aLBC) and biomarkers to identify candidates for high-resolution anoscopy (HRA).

Methods: This cross-sectional study included men who have sex with men with HIV. Participants underwent HRA, aLBC, and biomarker testing. Three screening procedures were compared with aLBC: biomarker alone, cytology and biomarker in all, and cytology and reflex biomarkers (biomarkers applied if aLBC results were atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion). Biomarkers included Linear Array (LA), LA for 14 high-risk human papillomavirus (LA 14 HR-HPV) genotypes, LA HPV-16, Hybrid Capture 2 (HC2), E6/E7 mRNA, and E6/E7 mRNA HPV-16.

Results: Of 354 participants, 179 (50.6%) had atypical squamous cells of undetermined significance or worse, requiring HRA (sensitivity, 80%; specificity, 57.3%; area under the curve, 0.687; reference, biopsy-proven HSIL). Cytology and reflex biomarkers per E6/E7 mRNA, LA 14 HR-HPV, and HC2 and the biomarker-alone procedure with HC2 showed comparable accuracy (sensitivities: 71.6%, 78.8%, 73.1%, 75.7%; specificities: 73.5%, 67.9%, 76.1%, 65.5%; areas under the curve: 0.726, 0.734, 0.746, 0.706) with fewer HRA referrals (number needed to diagnose: 2.2, 2.1, 2, 2.4).

Conclusions: Our findings suggest that E6/E7 mRNA, LA 14 HR-HPV, and HC2 in the cytology and reflex biomarkers procedure, as well as HC2 in the biomarker-alone procedure, can improve anal HSIL screening effectiveness.

Keywords: HPV; HSIL; anal cancer; anal dysplasia; men who have sex with men.

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Conflict of interest statement

Potential conflicts of interest. The Cancer Epidemiology Research Program, Catalan Institute of Oncology, has received sponsorship for grants from Merck & Co, Roche, GSK, IDT, Hologic, and Seegene that are not related to this study. Hologic generously provided the reagents for the Aptima assay and conducted the testing at no cost to our research project but did not play any role in the study design, conduction, or data analysis; in the writing of the report; and in the decision of submitting the article for publication. All other authors report no potential conflicts.

Figures

Figure 1.
Figure 1.
Screening procedures. aLBC, anal liquid-based cytology; ASC-H, atypical squamous cells that cannot exclude HSIL; ASC-US, atypical squamous cells of undetermined significance; HRA, high-resolution anoscopy; HSIL, high-grade squamous intraepithelial lesion; LSIL, low-grade squamous intraepithelial lesion; NILM, negative for intraepithelial lesion and malignancy.
See this image and copyright information in PMC

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