Does high-risk human papilloma virus genotyping of abnormal anal cytology improve detection of high-grade anal intraepithelial neoplasia?

Ann E Walts; Pradip Manna; Raymond C-K Chan; Spencer Kerley; Shikha Bose

doi:10.1016/j.jasc.2014.03.012

Does high-risk human papilloma virus genotyping of abnormal anal cytology improve detection of high-grade anal intraepithelial neoplasia?

J Am Soc Cytopathol. 2014 Sep-Oct;3(5):236-243. doi: 10.1016/j.jasc.2014.03.012. Epub 2014 Apr 4.

Authors

Ann E Walts¹, Pradip Manna², Raymond C-K Chan³, Spencer Kerley², Shikha Bose³

Affiliations

¹ Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California. Electronic address: walts@cshs.org.
² Molecular Pathology, Physicians Reference Laboratory, Overland Park, Kansas.
³ Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California.

PMID: 31051676
DOI: 10.1016/j.jasc.2014.03.012

Abstract

Introduction: High-risk (HR) human papillomavirus (HPV) testing is accepted as the standard of care for surveillance of cervical cancer. Its role in anal cancer is not clear. This study was therefore designed to determine if HR HPV genotyping is a useful adjunct in management of abnormal anal Papanicolaou (Pap) tests.

Materials and methods: HR HPV genotyping and virus quantification was performed on 101 residual anal Pap test samples (28 negative, 25 atypical squamous cells of undetermined significance [ASC], 34 low-grade squamous intraepithelial lesion [LSIL], 6 atypical squamous cells of undetermined significance, cannot exclude high-grade squamous intraepithelial lesion, and 8 high-grade squamous intraepithelial lesion) using multiplex real-time polymerase chain reaction. Results were correlated with cytodiagnosis and follow-up.

Results: HR HPV was detected in 82% (50% negative, 84% ASC, and 100% LSIL and above) cases. Multiple genotypes were present in 71% of cases. Genotype number and viral load correlated with the degree of anal cytologic abnormality. HPV 16, 18, and 45 were the most frequent genotypes detected. The high frequency of HR HPV in abnormal anal cytologies limits its use as an adjunct test. Anal Pap test samples with anal intraepithelial neoplasia 2/3 (AIN 2/3) on follow-up were positive for HPV 16 and/or 18 (HPV 16/18+) in 80% of cases. We hypothesize that testing for HPV 16/18 on the ASC and LSIL cases would have detected AIN 2/3 with a sensitivity of 81%, specificity of 43%, positive predictive value of 39%, and negative predictive value of 83%.

Conclusions: Our results with a small cohort suggest that genotyping for HPV 16/18 may be effective in identifying patients at high risk for anal cancer and in reducing the number of anoscopy referrals. Prospective studies with follow-up are warranted.

Keywords: Anal cytology; Anal intraepithelial neoplasia; Genotypes; Human papilloma virus; Multiplex polymerase chain reaction.