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. 2023 Feb 28;13(5):917.
doi: 10.3390/diagnostics13050917.

E6/E7 mRNA Expression of the Most Prevalent High-Risk HPV Genotypes in Cervical Samples from Serbian Women

Natasa Nikolic  1 , Branka Basica  1 , Aljosa Mandic  2   3 , Nela Surla  1 , Vera Gusman  1   4 , Deana Medic  1   4 , Tamas Petrovic  5 , Mirjana Strbac  1 , Vladimir Petrovic  1   6
Affiliations

E6/E7 mRNA Expression of the Most Prevalent High-Risk HPV Genotypes in Cervical Samples from Serbian Women

Natasa Nikolic et al. Diagnostics (Basel). .

Abstract

Cervical cancer caused by persistent infection with HR HPV genotypes is the second leading cause of death in women aged 15 to 44 in Serbia. The expression of the E6 and E7 HPV oncogenes is considered as a promising biomarker in diagnosing high-grade squamous intraepithelial lesions (HSIL). This study aimed to evaluate HPV mRNA and DNA tests, compare the results according to the severity of the lesions, and assess the predictive potential for the diagnosis of HSIL. Cervical specimens were obtained at the Department of Gynecology, Community Health Centre Novi Sad, Serbia, and the Oncology Institute of Vojvodina, Serbia, during 2017-2021. The 365 samples were collected using the ThinPrep Pap test. The cytology slides were evaluated according to the Bethesda 2014 System. Using a real-time PCR test, HPV DNA was detected and genotyped, while the RT-PCR proved the presence of E6 and E7 mRNA. The most common genotypes in Serbian women are HPV 16, 31, 33, and 51. Oncogenic activity was demonstrated in 67% of HPV-positive women. A comparison of the HPV DNA and mRNA tests to assess the progression of cervical intraepithelial lesions indicated that higher specificity (89.1%) and positive predictive value (69.8-78.7%) were expressed by the E6/E7 mRNA test, while higher sensitivity was recorded when using the HPV DNA test (67.6-88%). The results determine the higher probability of detecting HPV infection by 7% provided by the mRNA test. The detected E6/E7 mRNA HR HPVs have a predictive potential in assessing the diagnosis of HSIL. The oncogenic activity of HPV 16 and age were the risk factors with the strongest predictive values for the development of HSIL.

Keywords: E6; E7; HPV; Serbia; biomarker; cervical intraepithelial lesion.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Genotype-specific distribution of HR HPVs.
Figure 2
Figure 2
Age-specific analyses of the most prevalent HR HPV DNA in different cytological groups. NILM—negative for an intraepithelial lesion or malignancy; ASCUS—atypical squamous cells of unknown significance; LSIL—low-grade squamous intraepithelial lesions; HSIL—high-grade squamous intraepithelial lesions.
Figure 3
Figure 3
Flowchart presenting the study design. HR—high risk; HPV—human papillomavirus.
Figure 4
Figure 4
Prevalence of the most prevalent HR HPVs DNA and achieved oncogenic activity according to age (A) and cytology (B). NILM—negative for an intraepithelial lesion or malignancy; ASCUS—atypical squamous cells of unknown significance; LSIL—low-grade squamous intraepithelial lesions; HSIL—high-grade squamous intraepithelial lesions.
Figure 5
Figure 5
ROC curve of HR HPV and E6/E7 HR HPV tests in HSIL.
Figure 6
Figure 6
Correlation between the oncogenic activity of the HPV 16 genotype and cytology (A) and overall HPVs’ oncogenic activity and cytology (B). NILM (1), ASCUS (2), LSIL (3), HSIL (4), and Spearman’s correlation coefficient (ρ).
See this image and copyright information in PMC

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