Molecular epidemiology and pathogenic potential of underdiagnosed human papillomavirus types

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.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.Human papillomavirus (HPV) infections of the genital tract are highly prevalent in the population worldwide; indeed, it is estimated that the great majority of sexually active individuals become infected with one or more of these viruses in their lifetimes. Most conditions are transient and are cleared without consequences. However, in a small proportion of cases, infections associated with the so-called high-risk (HR) HPV types can persist in typical lesions with a high viral load for years, and a fraction of such lesions eventually progress to invasive malignancies. Although many cofactors normally concur in this process, the HPV type implicated (the type-specific viral oncogenes) and the inability of the immune system to clear the infection are by far the m