Human Papillomavirus E6/E7 oncogene transcripts as biomarkers for the early detection of cervical cancer

Cancer of the cervix uteri is the fourth most common cancer worldwide with a high mortality rate. Due to limitations of the existing methods, alternative methods for triage are needed for early detection of cervical cancer precursors before progression to high-grade disease. The aim of this study was to evaluate human papillomavirus (HPV) E6/E7 oncogene expression as markers for early identification of cervical cancer risk in women with minor cytological abnormalities and in those with negative cytology. The detection of HPV was done using PCR and confirmed by southern hybridization. The high-risk (HR) and low-risk HPV types were identified by HPV typing. HPV DNA-positive patients were further tested for markers of oncogene expression by real-time PCR. Out of the women screened, 54/512 (10.54%) women tested positive for HPV infection. HR HPV DNA was found in 32/485 (6.60%) women with normal cytology (Pap negative) and 22/27 (81.5%) atypical squamous cells of undetermined significance/low-grade intraepithelial lesion cases. HR HPV E6/E7 oncogene transcripts were detected in 36/512 (7.03%) patients. The positivity rate of E6/E7 messenger RNA (mRNA) was 2.48% (12/485) in normal cervical cytology group and 88.9% (24/27) in abnormal cervical cytology group. The HPV E6/E7 mRNA test sensitivity was found to be 88.89% and specificity was 97.53%. In comparison, the sensitivity of the HPV DNA test was found to be 81.48% and specificity was 93.40%. In conclusion, E6 and E7 transcripts could provide a sensitive, early predictor of cervical cancer risk in women with normal cytology and minor cytological alterations.