Evaluation of HPV-Related Biomarkers in Anal Cytological Samples from HIV-Uninfected and HIV-Infected MSM

Men who have sex with men (MSM) harbor the highest risk for anal carcinoma, mainly caused by Human Papillomavirus (HPV). The use of HPV-related biomarkers in the screening for this neoplasia is still debated. We assessed the association between high-risk (hr)HPV DNA, HPV16/18 DNA, hrHPV E6/E7 mRNA, and p16/Ki-67 with cytological abnormalities (any grade) and high-grade intraepithelial lesions (HSIL) in HIV-uninfected and HIV-infected MSM. Overall, 150 cytological samples in PreservCyt (Hologic), with a negative to HSIL report, were analyzed for hrHPV DNA, hrHPV E6/E7 mRNA, and p16/Ki-67 using the Linear Array (Roche), Aptima (Hologic), and CINtec® PLUS (Roche) assays. In HIV-infected MSM, positivity for all the biomarkers significantly increased with the cytological grade. In both populations, the association of hrHPV E6/E7 mRNA and p16/Ki-67 positivity with HPV16 did not differ significantly compared to hrHPVs other than HPV16. In HIV-uninfected MSM, the odds of having an HSIL increased approximately six times for the p16/Ki-67 positive cases. In HIV-infected individuals, all the biomarkers showed a significant association with HSIL, except for hrHPV DNA, with the strongest association observed for p16/Ki-67. The odds of HSIL increased almost 21 times in those positive for this biomarker. Our results encourage further investigation on the use of p16/Ki-67 dual staining in anal cancer screening for HIV-uninfected and HIV-infected MSM.

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Comparative Evaluation of P16, Ki-67, and Shape-correlated Genes as Biomarkers for Cervical High-grade Squamous Intraepithelial Lesions

10.21203/rs.3.rs-33881/v1 ◽

2020 ◽

Author(s):

hengzi Sun ◽

Shuhong Li ◽

Dongyan Cao ◽

Jiaxin Yang ◽

Peng Peng ◽

...

Keyword(s):

Sensitivity And Specificity ◽

Comparative Evaluation ◽

Referral Rate ◽

The Other ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Ki 67 ◽

Intraepithelial Lesions ◽

Dual Staining

Abstract Background:Colposcopy was referred in cases with severe abnormalities in co-testing. However, approximately 60%-80% patients did not receive proper benefits. Although p16/Ki67 dual staining reduced the referral rate, its sensitivity and specificity need to be enhanced. Methods:The expression of p16, Ki-67, SMAD3, YAP1, RELA were evaluated inthe colposcopy referral population. Results:The sensitivity and specificity of p16+ combined with Ki-67+ for predicting CIN2+ were 62.1% and 89.5%, respectively. p16+ combined with YAP1+ and/or RELA+ provided a sensitivity and specificity of 70.9% and 89.5%, respectively, while 72.8% and 86.4% were achieved by p16+ combined with YAP1+ and/or SMAD3+ and/or RELA+. In HPV16/18+ and LSIL subgroups, the sensitivity and specificity of p16+ combined with Ki-67+ for predicting CIN2+ were 67.7% and 87.6%, respectively, for the former group and 58.6%, 88.8%, respectively, for the latter group, whereas those of RELA alone were 76.9% and 90.5%, respectively, and 82.8% and 92.1%, respectively. p16+, YAP1+/RELA+ showed a better performance for predicting CIN2+ with a better sensitivity (86.7% vs. 52.2%, p=0.028) and considerable specificity (86.7% vs. 90.0%, p=0.486) in the other HPV+ combined with ASCUS groupthan were achieved by p16+ combined with Ki-67+. RELA+ and the combination of p16 and RELA/YAP1 also provided the Max AUC area. Conclusions:Our study shows that RELA and the combination of p16 and RELA/YAP1 achieved better sensitivity and specificity for detecting morphologically CIN2+ lesions.

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Evaluation of p16/Ki-67 dual staining compared with HPV genotyping in anal cytology with diagnosis of ASC-US for detection of high-grade anal intraepithelial lesions

Journal of Cytology ◽

10.4103/joc.joc_131_18 ◽

2019 ◽

Vol 36 (3) ◽

pp. 152

Author(s):

Mojgan Devouassoux-Shisheboran ◽

Maxime Pichon ◽

Marie Joly ◽

Frédérique Lebreton ◽

Medhi Benchaïb ◽

...

Keyword(s):

High Grade ◽

Ki 67 ◽

Hpv Genotyping ◽

Anal Cytology ◽

Intraepithelial Lesions ◽

Dual Staining

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Comparison of Hybribio GenoArray and Roche Human Papillomavirus (HPV) Linear Array for HPV Genotyping in Anal Swab Samples

Journal of Clinical Microbiology ◽

10.1128/jcm.02274-14 ◽

2014 ◽

Vol 53 (2) ◽

pp. 550-556 ◽

Cited By ~ 5

Author(s):

Huey Chi Low ◽

Michelle I. Silver ◽

Brandon J. Brown ◽

Chan Yoon Leng ◽

Magaly M. Blas ◽

...

Keyword(s):

Human Papillomavirus ◽

Anal Cancer ◽

Linear Array ◽

Kappa Statistics ◽

Hpv Dna ◽

Resource Limited ◽

Hpv Genotypes ◽

Anal Swab ◽

Sex With Men ◽

Anal Cancer Screening

Human papillomavirus (HPV) is causally associated with anal cancer, as HPV DNA is detected in up to 90% of anal intraepithelial neoplasias and anal cancers. With the gradual increase of anal cancer rates, there is a growing need to establish reliable and clinically relevant methods to detect anal cancer precursors. In resource-limited settings, HPV DNA detection is a potentially relevant tool for anal cancer screening. Here, we evaluated the performance of the Hybribio GenoArray (GA) for genotyping HPV in anal samples, against the reference standard Roche Linear Array (LA). Anal swab samples were obtained from sexually active men who have sex with men. Following DNA extraction, each sample was genotyped using GA and LA. The overall interassay agreement, type-specific, and single and multiple genotype agreements were evaluated by kappa statistics and McNemar's χ2tests. Using GA and LA, 68% and 76% of samples were HPV DNA positive, respectively. There was substantial interassay agreements for the detection of all HPV genotypes (κ = 0.70, 86% agreement). Although LA was able to detect more genotypes per sample, the interassay agreement was acceptable (κ = 0.53, 63% agreement). GA had poorer specific detection of HPV genotypes 35, 42, and 51 (κ < 0.60). In conclusion, GA and LA showed good interassay agreement for the detection of most HPV genotypes in anal samples. However, the detection of HPV DNA in up to 76% of anal samples warrants further evaluation of its clinical significance.

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Relevance of the Pap Test: A Report of HPV-DNA Test-Negative High-Grade Squamous Intraepithelial Lesions of the Female Lower Genital Tract

Acta Cytologica ◽

10.1159/000448470 ◽

2016 ◽

Vol 60 (5) ◽

pp. 445-450 ◽

Cited By ~ 3

Author(s):

Yiang Hui ◽

Katrine Hansen ◽

Jayasimha Murthy ◽

Danielle Chau ◽

C. James Sung ◽

...

Keyword(s):

High Risk ◽

Pap Test ◽

Human Papillomaviruses ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Cytologic Examination ◽

Dna Test ◽

Hpv Dna ◽

Intraepithelial Lesions ◽

Hpv Dna Test

Objective: A vast majority of cervicovaginal intraepithelial lesions are caused by high-risk human papillomaviruses (HPVs). The Pap test has been the sole method used for the screening of cervicovaginal squamous intraepithelial lesions (SIL). Recently, the FDA approved an HPV-DNA assay as a method of primary screening. We report on a series of FDA-approved HPV-DNA test-negative SIL with HPV genotyping, using an alternative method on the corresponding surgical biopsy specimens. Study Design: A retrospective review identified cytology-positive HPV-negative cases over a 15-month period at a tertiary care gynecologic oncology institution. Corresponding biopsies were reviewed and genotyped for high-risk HPVs. Results: Of the 18,200 total cases, 17 patients meeting the study criteria were selected with 27 surgical specimens corresponding to their cytologic diagnoses. Four patients with high-grade lesions were identified, 3 of whom (75%) were positive for HPV. One of these 4 patients (25%) showed high-grade SIL on biopsies from 4 separate sites in the cervix and vagina. Multiviral HPV infections were frequent. Conclusions: We discuss the relevance of cotesting for screening cervical SILs and emphasize that false-negative results are possible with the FDA-approved HPV screening assay, also in patients with high-grade SIL. These cases may be detectable by cytologic examination and this suggests that the Pap test remains an important diagnostic tool.

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Determinants of high-grade anal intraepithelial lesions in HIV-positive men having sex with men

Papillomavirus Research ◽

10.1016/j.pvr.2018.07.008 ◽

2018 ◽

Vol 5 ◽

pp. S3

Author(s):

Isabelle Etienney ◽

Laurent Siproudhis ◽

Lionel Piroth ◽

Isabelle Poizot-Martin ◽

Sylvie Radenne ◽

...

Keyword(s):

Hiv Positive ◽

High Grade ◽

Sex With Men ◽

Intraepithelial Lesions ◽

Hiv Positive Men

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8. Human papillomavirus mRNA testing for the detection of anal high-grade squamous intraepithelial lesions in HIV-positive men who have sex with men

Sexual Health ◽

10.1071/shv10n6ab8 ◽

2013 ◽

Vol 10 (6) ◽

pp. 573

Author(s):

Elena Sendagorta Cudós ◽

Maria P. Romero Gomez ◽

Beatriz Hernandez Novoa ◽

Ander Mayor ◽

Jose I. Bernardino De La Serna ◽

...

Keyword(s):

Predictive Value ◽

Screening Program ◽

University Hospital ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Cross Sectional ◽

Hpv Dna ◽

Hpv E6 ◽

Anal Cytology ◽

Intraepithelial Lesions

Background Currently, screening for anal high-grade squamous intraepithelial lesions (HSIL) relies on anal cytology and high-resolution anoscopy (HRA). 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 HIV-infected patients, in comparison to DNA-HR-HPV and anal cytology. Methods: 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, HRA and histology were analysed. HR-HPV-DNA detection was performed by means of the CLART HPV2 assay (GENOMICA SAU.). E6/E7-mRNA detection of HR-HPV types 16, 18, 31, 33 and 45 was performed using the NucliSENS-EasyQ assay (BioMérieux, Marcy l’Etoile, France). Results: HR-HPV DNA and HPV E6/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 with 97.9%, 31.5%, 55.4% and 94.4%, respectively, for HR-HPV DNA testing and 83%, 40.7%, 54.9%, 73.3%, respectively, for cytology testing. Conclusions: In comparison with the other tests, the NucliSENS EasyQ HPV assay yielded a lower clinical sensitivity but a higher clinical specificity and PPV for the detection of anal HSIL in MSM HIV-infected patients.

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