Diagnostic Utility of HPV16 E6 mRNA or E7 mRNA Quantitative Expression for Cervical Cells of Patients with Dysplasia and Carcinoma

Abstract

Current human papillomavirus (HPV)16 DNA testing has high sensitivity but low specificity, while mRNA testing (qualitative) improves the specificity. However, both techniques are not able to discriminate between transient and persistent infections. To overcome the disadvantages, we quantitatively detected E6 and E7 mRNAs by quantitative real-time polymerase chain reaction (qRT-PCR) in cervical brushing cells from 87 HPV16+ and 31 HPV16− patients. Our results showed that the expression levels of E6 mRNA or E7 mRNA were significantly increased in HPV16-positive cases than that in the negative cases. Furthermore, in HPV16+ cases, the expression levels of E6 mRNA were significantly increased in invasive cancer compared with high-grade squamous intraepithelial lesion (HSIL; p < 0.01), and HSIL compared with low-grade squamous intraepithelial lesion (LSIL; p < 0.01). There were no significant changes between LSIL and benign lesions. The expression levels of E7 mRNA presented no significant difference among the above-mentioned four groups. To test whether qRT-PCR can discriminate between transient and persistent infections, 57 HPV16+ patients were followed up for 1 year, and our results demonstrated that the expression levels of both E6 mRNA and E7 mRNA in the persistent infection group were significantly increased relative to the transient infection group (p < 0.01 or 0.05). Thus, a quantitative detection of the expression levels of E6 mRNA in cervical brushing cells may not only be used as an ancillary tool to cytological diagnosis of cervical neoplasia, but may also help to determine the severity of the lesions and the triage of transient infection.

Epidemiology and persistence of cervical human papillomavirus infection among outpatient women in Heilongjiang province: A retrospective cohort study

“…15 shown previously to be highly reliable, sensitive, and accurate. 24,25,31 We chose this method to minimize false-negative results and provide clinically relevant reference values.…”

“…3 However, 12 types (HPV16, 18,31,33,35,39,45,51,52, 56, 58, and 59) are the etiological agents of cancer, and International Agency for Research on Cancer classified these HPVs as Hr-HPVs. 2 A 2012 study of cervical cancer indicated that 90% of patients with cervical cancer were carrying HPV type 6,11,16,18,31,33,45,52, and/or 58, with 71% of patients carrying types 16 and 18 globally, which are considered to be particularly carcinogenic. 4 HPV exposure is very high, with some 80% of sexually active women acquiring an HPV infection during their lifetimes.…”

miR-4454 up-regulated by HPV16 E6/E7 promotes invasion and migration by targeting ABHD2/NUDT21 in cervical cancer

“…In HPV-positive cervical cancers, all of the malignant cells contain at least one copy of the viral genome with transcriptional activity [7,8]. Recent studies have shown that non-coding microRNAs (miRNAs) are also regulated by E6 and E7 at the transcriptional and post-transcriptional level [6,[9][10][11][12][13].…”

Increased risk for development of severe cervical dysplasia among postmenopausal women with normal cytology and presence of HPV mRNA

“…There is evidence in the literature that the level of the mRNA copies increases proportionally to the severity of the cervical lesion (18). On the contrary, a negative HPV mRNA result in combination with a positive HPV-DNA outcome seems to reflect the presence of an inactive HR-HPV infection with low or absent viral replication.…”

“…HPV types:16,18,31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and the probable high-risk type 68 (A and B) as well as the possibly high-risk types 26, 53, 66, 67, 69, 73 and 82 as described by IARC classification from year 2012(9). In the present study, probable and possible HR-HPV types were classified as HR-HPV types.The HPV E6/E7 mRNA (APTIMA) assay (Hologic, Inc.) detects qualitatively E6/E7 mRNA from 14 HR-HPV types:16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.…”