Use of hTERT and HPV E6/E7 mRNA RT-qPCR TaqMan assays in combination for diagnosing high-grade cervical lesions and malignant tumors

Objectives: Human papillomavirus (HPV) is a major cause of cervical cancer, which is the second most common cancer in women. HPV E6 initiates degradation of cellular tumor suppressor protein p53, induces human telomerase reverse transcriptase (hTERT) activity, and then leads to progressive cervical carcinogenesis. Methods: In this study, the CervicGen HPV RT-qDX assay (Optipharm, Osong, Republic of Korea), which detects 16 HPV high-risk subtypes (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, and 69), and the CervicGen hTERT RT-qDX assay (Optipharm) were evaluated using 545 ThinPrep (Hologic, Bedford, MA) Papanicolaou samples. Results: The positivity for the HPV E6/E7 messenger RNA (mRNA) assay was 94.4%, 95.2%, 82.4%, 46.5%, 25.0%, and 1.1% in squamous cell carcinomas, high-grade squamous intraepithelial lesions (HSILs), atypical squamous cells - cannot exclude HSIL, low-grade squamous intraepithelial lesions, atypical squamous cells of undetermined significance, and normal cytology samples, respectively. Five cervical intraepithelial neoplasia grade 2+ samples were not detected by the HPV E6/E7 mRNA assay, but they exhibited positive signals in the hTERT mRNA assay. Notably, the hTERT mRNA expression level was increased in high-grade cervical lesions but was very low in all 288 normal samples. Conclusions: These data suggest that the combination of HPV E6/E7 and hTERT mRNA expression levels could be used in a complementary manner in diagnosing high-grade cervical lesions and malignant tumors and might be useful as a predictive marker in monitoring low-grade cervical lesions.