Detection of Multiple Human Papillomavirus Genotypes in Anal Carcinoma

Sonia Ramamoorthy,John M Carethers,Linda Luo,Qing Lu,Katsumi Miyai,Yu-Tsueng Liu

doi:10.1186/1750-9378-5-17

Abstract

Infection with human papillomavirus (HPV) is a major risk factor for development of anal squamous cell carcinoma. Despite over 100 genotypes of the virus, HPV 16 and 18 are considered pathogenic as they are seen in the majority of cervical and anal cancers. We have employed a custom microarray to examine DNA for several HPV genotypes. We aimed to determine the accuracy of our microarray in anal cancer DNA for HPV genotypes compared to the DNA sequencing gold standard.MethodsWe utilized a sensitive microarray platform to classify 37 types of mucosal HPVs including 14 known high-risk and 23 low-risk types based on cervical cancer data. We utilized DNA from pathologically confirmed cases of anal squamous cell carcinoma. All samples underwent microarray HPV genotyping and PCR analysis.ResultsHPV was detected in 18/20 (90%) anal cancers. HPV genotypes 16 and 18 were present in the majority of specimens, with HPV 16 being the most common. Eighty percent of anal cancers had at least two HPV types. Ten percent of cases (2/20) tested negative using our microarray; DNA sequencing confirmed the lack of presence of HPV DNA in these samples.ConclusionsMicroarray technology is an accurate way to screen for various genotypes of HPV in anal cancer, with 100% correlation with genomic DNA detection of HPV. The majority of anal cancers in our study associated with pathogenic HPV 16 and/or 18. Other HPV genotypes are present simultaneously with HPV 16 and 18, and might contribute to its pathogenesis.

Highlights

Squamous cell cancer of the anus is increasing in frequency in the general population in the United States, Europe and South America [1]
Microarray technology is an accurate way to screen for various genotypes of human papillomavirus (HPV) in anal cancer, with 100% correlation with genomic DNA detection of HPV
The majority of anal cancers in our study associated with pathogenic HPV 16 and/or 18

Summary

Introduction

Squamous cell cancer of the anus (anal cancer) is increasing in frequency in the general population in the United States, Europe and South America [1]. There were an estimated 4000 new cases in 2003 in the United States [2], and that number was estimated to be 5290 for 2009 [3]. Despite the increasing numbers of patients with anal cancer, little has changed in the paradigm for the treatment and outcomes from this disease. Anal cancer was initially thought to develop from conditions of chronic inflammation such as perianal Crohn’s disease; genital viral infection with HPV with or without a concomitant immunocompromised condition has been shown to be the major risk factor for the development of anal dysplasia, a precursor lesion to cancer DNA for HPV types using DNA sequencing techniques as the gold standard

Objectives

Methods

Results

Conclusion