Molecular epidemiology and pathogenic potential of underdiagnosed human papillomavirus types

Stefano Menzo¹ , Andrea Ciavattini² , Patrizia Bagnarelli¹ , Katia Marinelli¹ , Stefano Sisti³ and Massimo Clementi⁴

¹Institute of Microbiology, Università Politecnica delle Marche, Ancona, Italy

²Institute of Obstetrics and Gynecology, Università Politecnica delle Marche, Ancona, Italy

³Institute of Pathology, Università Politecnica delle Marche, Ancona, Italy

⁴Institute of Microbiology, Università Vita-Salute San Raffaele, Milano, Italy

author email corresponding author email

BMC Microbiology 2008, 8:112doi:10.1186/1471-2180-8-112


Published:	4 July 2008

Abstract

Background

Human papillomavirus (HPV) tests are crucial diagnostic tools for the prevention of neoplastic lesions of the uterine cervix. However most commercial methods are designed to detect high-risk (HR) HPV types and a limited selection of low-risk ones, thus missing a fair number of intermediate/low-risk types. As a result, many HPV infections remain undiagnosed, generating distrust in virological diagnosis among gynaecologists, who continue to rely preferentially on cytological and colposcopic findings.

Results

In this study, we tested 6,335 consecutive clinical samples, most of them from Italian patients with cytological abnormalities. The samples, collected in 2000–2007, were analyzed using PCR amplification of a 173–206 bp (depending on HPV type) conserved region in the L1 open reading frame, restriction endonuclease analysis and, where required, sequence analysis for type determination. Analysis of a smaller male sample and long term follow-up of a few female subjects was also performed. A total of 2,161 samples tested positive for HPV DNA (32.1%); 21.3% of them were mixed infections. Overall, 59 known and 2 unknown HPV types were detected. Their relative prevalence was calculated; notably, types not clearly identifiable using the most common commercial method accounted for 36% of infections. Clinical findings associated with the underdiagnosed types ranged from H-SIL to low-grade abnormalities, although none of these infections resulted in invasive cancer.

Conclusion

Given the high prevalence of some underdiagnosed HPV types in the population (principally HPV53, HPV66, HPV84, and HPV87) and their frequent association with cytological abnormalities, techniques capable of detecting and typing them would prove extremely useful.