Human Papillomavirus Molecular Testing in Women with Low Grade Cervical Lesions: Experience from an Italian Hospital

Background: In recent years, efforts have been made to identify molecular markers as potential screening tools in the early detection of cervical cancer precursors. Patients and Methods: One-hundred-eighty-two women admitted to the Colposcopy Unit of Tor Vergata University Hospital were enrolled in this study. The inclusion criteria were: i) Pap test with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL); ii) normal cytology but human papillomavirus (HPV) DNA test positive for at least one of the most frequently detected five high-risk HPV types (16, 18, 31, 33 and 45). HPV DNA was detected with the HPV Sign kit and the type was assigned by pyrosequencing using the PyroMark ID System. E6/E7 transcripts of the high-risk HPV types 16, 18, 31, 33 and 45 were detected by the NucliSense EasyQ HPV kit. Results: Overall, 90 (49.5%) patients were HPV-DNA negative, whereas 92 (50.5%) were HPV-DNA positive. Single infections were detected in 55 women: HPV 16 ranked first (56.4%), followed by HPV 18 (21.8%), HPV 31 (9%), HPV 33 (7.3%), and HPV 45 (5.5%). Co-infections were detected in 37/92 (40.2%) positive cases; HPV 16 was detected most frequently (27/37), followed by HPV 18 and 31. All patients underwent HPV RNA testing: 47/182 (25.8%) tested positively while 135/182 (74.2%) were negative. HPV 16 E6/E7 transcripts was the most frequently detected. Conclusion: Detection of HPV E6/E7 oncogenic transcripts may be used as a molecular biomarker in women with ASCUS or LSIL to help identify women at risk of disease progression. Cervical cancer is the second most common type of cancer in women worldwide. The majority of cases occur in the developing world, where, in some countries, cervical cancer represents the primary cause of cancer-related death (1). Human papillomavirus (HPV) is the recognized etiological agent of cervical cancer, being detected in almost all cervical cancer cases (2). To date, 120 human HPVs have been identified (3) and based on epidemiological studies, they are classified as low-risk types and high-risk types. Low-risk types are associated commonly with benign lesions such as warts and condylomata, while high-risk types are associated with high-grade lesions and cervical cancer (4).