The role of L1 and L2 capsid proteins of human papillomavirus in the differential diagnosis of squamous intraepithelial lesions
Dobrovolskaya D.A., Bayramova G.R., Asaturova A.V., Badlaeva A.S., Tregubova A.V.
Objective: To evaluate and analyze the expression of L1 and L2 proteins of human papillomavirus (HPV) using the techniques of immunohistochemistry (IHC) and L1 immunocytochemistry (ICC) for differential diagnosis of cervical squamous intraepithelial lesions.
Materials and methods: The cross-sectional study included 128 patients who presented to the Department of Outpatient Clinical Research Development of the National Medical Research Centre for Obstetrics, Gynecology and Perinatology in Moscow in the period from January 2022 to January 2023. The patients met the inclusion and exclusion criteria. Depending on the results of cervical cytology, all examined patients were divided into four groups: group 1 included 36 women with NILM cytology, group 2 consisted of 31 patients with ASC-US cytology, group 3 included 31 patients with LSIL cytology, and group 4 consisted of 30 patients with HSIL cytology. All patients underwent cytological, colposcopic and histological examination as well as IHC and ICC to determine the expression level of HPV L1 and L1/L2 viral proteins, respectively.
Results: The expression of HPV L1 was statistically significantly more frequent and revealed by ICC technique in the LSIL group (65.6%) compared to HSIL (20%) and NILM (19.4%) (Pearson’s χ2, p<0.001). LSIL was 2.1 times more likely to be detected by cytological examination among all L1-positive samples compared to L1-negative samples (95% CI: 1.98-10.87, p<0.001). The use of IHC technique made it possible to detect the expression of L1 viral protein in 72.9% of LSIL (CIN1) cases, which was statistically significantly more frequent than in other study groups (p<0.001). In the group of histologically verified LSIL (CIN1), positive expression of HPV L2 protein was observed in 48.8% of cases.
Conclusion: The use of HPV L1 and L2 capsid proteins can significantly improve the differential diagnosis of mild squamous intraepithelial lesions.
Authors’ contributions: Dobrovolskaya D.A., Bayramova G.R., Asaturova A.V. – developing the design of the study, review of publications on the issue of the study and their translation, statistical analysis of the obtained data, writing the text of the manuscript; Dobrovolskaya D.A., Badlaeva A.S., Tregubova A.V. – obtaining the data for analysis; Asaturova A.V., Bayramova G.R. – structuring and editing the article.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The study was carried out with the financial support of the Russian Foundation for Basic Research and the Moscow City Government within the framework of scientific project No. 21-315-70048, “Study of the role of viral replicative early response proteins of human papillomavirus in modulation of signaling pathways of cervical epitheliocytes in initial forms of cervical intraepithelial squamous lesions using neural network analysis methods”.
Ethical Approval: The study was approved by the Ethical Review Board of the Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow.
Patient Consent for Publication: The patients signed informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator.
For citation: Dobrovolskaya D.A., Bayramova G.R., Asaturova A.V., Badlaeva A.S., Tregubova A.V. The role of L1 and L2 capsid proteins of human papillomavirus in the differential diagnosis of squamous intraepithelial lesions.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (2): 81-90 (in Russian)
https://dx.doi.org/10.18565/aig.2024.298
Keywords
human papillomavirus (HPV)
cervical squamous intraepithelial lesions (SIL)
differential diagnosis of SIL
capsid viral proteins
immunocytochemistry
immunohistochemistry
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Received 20.11.2024
Accepted 13.02.2025
About the Authors
Darya A. Dobrovolskaya, PhD student, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 4 Ac. Oparin str., Moscow, 117997, Russia, +7(916)400-67-68,doc@ddoborovolskaya.ru, https://orcid.org/0000-0002-1409-9959
Guildana R. Bayramova, Dr. Med. Sci., Honored Physician of the Russian Federation, Professor at the Department of Obstetrics and Gynecology of the Department of Vocational Education, Head of Clinical Work at the Scientific Polyclinic Department, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 4 Ac. Oparin str., Moscow, 117997, Russia, +7(926)660-48-77, bayramova@mail.ru, https://orcid.org/0000-0003-4826-661X
Alexandra V. Asaturova, Dr. Med. Sci., Head of the 1st Pathology Department, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 4 Ac. Oparin str., Moscow, 117997, Russia, a_asaturova@oparina4.ru, https://orcid.org/0000-0001-8739-5209
Alina S. Badlaeva, PhD, Pathomorphologist at the 1st Pathoanatomical Department, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 4 Ac. Oparin str., Moscow, 117997, Russia, a_badlaeva@oparina4.ru, https://orcid.org/0000-0001-5223-9767
Anna V. Tregubova, Pathomorphologist at the 1st Pathoanatomical Department V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 4 Ac. Oparin str., Moscow, 117997, dr.a.tregubova@gmail.com, https://orcid.org/0000-0003-4601-1330
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