The role of L₁ and L₂ capsid proteins of human papillomavirus in the differential diagnosis of squamous intraepithelial lesions
- Autores: Dobrovolskaya D.A.1, Bayramova G.R.1, Asaturova A.V.1, Badlaeva A.S.1, Tregubova A.V.1
-
Afiliações:
- Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
- Edição: Nº 2 (2025)
- Páginas: 81-90
- Seção: Original Articles
- URL: https://journal-vniispk.ru/0300-9092/article/view/291071
- DOI: https://doi.org/10.18565/aig.2024.298
- ID: 291071
Citar
Resumo
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.
Texto integral
##article.viewOnOriginalSite##Sobre autores
Darya Dobrovolskaya
Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Autor responsável pela correspondência
Email: doc@ddoborovolskaya.ru
ORCID ID: 0000-0002-1409-9959
PhD student
Rússia, 4 Ac. Oparin str., Moscow, 117997
Guildana Bayramova
Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: bayramova@mail.ru
ORCID ID: 0000-0003-4826-661X
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
Rússia, 4 Ac. Oparin str., Moscow, 117997Alexandra Asaturova
Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: a_asaturova@oparina4.ru
ORCID ID: 0000-0001-8739-5209
Dr. Med. Sci., Head of the 1st Pathology Department
Rússia, 4 Ac. Oparin str., Moscow, 117997Alina Badlaeva
Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: a_badlaeva@oparina4.ru
ORCID ID: 0000-0001-5223-9767
PhD, Pathomorphologist at the 1st Pathoanatomical Department
Rússia, 4 Ac. Oparin str., Moscow, 117997Anna Tregubova
Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: dr.a.tregubova@gmail.com
ORCID ID: 0000-0003-4601-1330
Pathomorphologist at the 1st Pathoanatomical Department
Rússia, 4 Ac. Oparin str., Moscow, 117997Bibliografia
- Atla B., Uma P., Shamili M., Kumar S. Cytological patterns of cervical pap smears with histopathological correlation. Int. J. Res. Med. Sci. 2015; 3(8): 1911-6. https://dx.doi.org/10.18203/2320-6012.ijrms20150300.
- Koliopoulos G., Nyaga V.N., Santesso N., Bryant A., Martin-Hirsch P.P., Mustafa R.A. et al. Cytology versus HPV testing for cervical cancer screening in the general population. Cochrane Database Syst. Rev. 2017; 8(8): CD008587. https://dx.doi.org/10.1002/14651858.CD008587.pub2.
- Singhal A., Raina R., Verma S., Verma A. Predictive accuracy of cervical cytology and colposcopy in diagnosing premalignant and malignant cervical lesions: A hospital-based study from the sub-Himalayan region of Indian subcontinent. CHRISMED Journal of Health and Research. 2019, 6(1): 39-43. https:// dx.doi.org/10.4103/cjhr.cjhr_51_18.
- Wright T.C. Jr., Stoler M.H., Behrens C.M., Sharma A., Sharma K., Apple R. Interlaboratory variation in the performance of liquid-based cytology: insights from the ATHENA trial. Int. J. Cancer. 2014; 134(8): 1835-43. https:// dx.doi.org/10.1002/ijc.28514.
- Kyrgiou M., Athanasiou A., Kalliala I.E.J., Paraskevaidi M., Mitra A., Martin-Hirsch P.P. et al. Obstetric outcomes after conservative treatment for cervical intraepithelial lesions and early invasive disease. Cochrane Database Syst. Rev. 2017; 11(11): CD012847. https://dx.doi.org/10.1002/ 14651858.CD012847.
- Kyrgiou M., Koliopoulos G., Martin-Hirsch P., Arbyn M., Prendiville W., Paraskevaidis E. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet. 2006; 367(9509): 489-98. https://dx.doi.org/10.1016/ S0140-6736(06)68181-6.
- Nayar R., Wilbur D.C. The Pap test and Bethesda 2014. Cancer Cytopathol. 2015; 123(5): 271-81. https://dx.doi.org/10.1002/cncy.21521.
- Bin H., Ruifang W., Ruizhen L., Zhihong L., Juan L., Chun W. et al. Detention of HPV L1 capsid protein and hTERC gene in screening of cervical cancer. Iranian Journal of Basic Medical Sciences. 2013; 16(6): 797-802. https:// dx.doi.org/10.22038/ijbms.2013.997.
- Lee S.J., Lee A.W., Kang C.S., Park J.S., Park D.C., Ki E.Y. et al. Clinicopathological implications of human papilloma virus (HPV) L1 capsid protein immunoreactivity in HPV16-positive cervical cytology. Int. J. Med. Sci. 2013; 11(1): 80-6. https://dx.doi.org/10.7150/ijms.5585.
- Choi Y.J., Lee A., Kim T.J., Jin H.T., Seo Y.B., Park J.S. et al. E2/E6 ratio and L1 immunoreactivity as biomarkers to determine HPV16-positive high-grade squamous intraepithelial lesions (CIN2 and 3) and cervical squamous cell carcinoma. J. Gynecol. Oncol. 2018; 29(3): e38. https://dx.doi.org/10.3802/jgo.2018.29.e38.
- Norman I., Hjerpe A., Andersson S. High-risk HPV L1 capsid protein as a marker of cervical intraepithelial neoplasia in high-risk HPV-positive women with minor cytological abnormalities. Oncol. Rep. 2013; 30(2): 695-700. https://dx.doi.org/10.3892/or.2013.2538.
- Mehlhorn G., Obermann E., Negri G., Bubendorf L., Mian C., Koch M. et al. HPV L1 detection discriminates cervical precancer from transient HPV infection: a prospective international multicenter study. Mod. Pathol. 2013; 26(7): 967-74. https://dx.doi.org/10.1038/modpathol.2012.233.
- Melsheimer P., Kaul S., Dobeck S., Bastert G. Immunocytochemical detection of HPV high-risk type L1 capsid proteins in LSIL and HSIL as compared with detection of HPV L1 DNA. Acta Cytol. 2003; 47(2): 124-8. https:// dx.doi.org/10.1159/000326491.
- Huang M.Z., Li H.B., Nie X.M., Wu X.Y., Jiang X.M. An analysis on the combination expression of HPV L1 capsid protein and p16INK4a in cervical lesions. Diagn. Cytopathol. 2010; 38(8): 573-8. https://dx.doi.org/10.1002/dc.21258.
- Ki E.Y., Park J.S., Lee A., Kim T.J., Jin H.T., Seo Y.B. et al. Utility of human papillomavirus L1 capsid protein and HPV test as prognostic markers for cervical intraepithelial neoplasia 2+ in women with persistent ASCUS /LSIL cervical cytology. Int. J. Med. Sci. 2019; 16(8): 1096-101. https://dx.doi.org/10.7150/ijms.31163.
- Haltas H., Bayrak R., Yenidunya S., Yildirim U. The immunohistochemical detection of P16 and HPV L1 capsid protein on cell block sections from residual PapSpin liquid-based gynecology cytology specimens as a diagnostic and prognostic tool. Eur. Rev. Med. Pharmacol. Sci. 2012; 16(11): 1588-95.
- Yemelyanova A., Gravitt P.E., Ronnett B.M., Rositch A.F., Ogurtsova A., Seidman J. et al. Immunohistochemical detection of human papillomavirus capsid proteins L1 and L2 in squamous intraepithelial lesions: potential utility in diagnosis and management. Mod. Pathol. 2013; 26(2): 268-74. https:// dx.doi.org/10.1038/modpathol.2012.156.
- Negri G., Bellisano G., Zannoni G.F., Rivasi F., Kasal A., Vittadello F. et al. p16 ink4a and HPV L1 immunohistochemistry is helpful for estimating the behavior of low-grade dysplastic lesions of the cervix uteri. Am. J. Surg. Pathol. 2008; 32(11): 1715-20. https://dx.doi.org/10.1097/PAS.0b013e3181709fbf.
- Doorbar J. The papillomavirus life cycle. J. Clin. Virol. 2005; 32 Suppl 1: S7-15. https://dx.doi.org/10.1016/j.jcv.2004.12.006.
- Galgano M.T., Castle P.E., Atkins K.A., Brix W.K., Nassau S.R., Stoler M.H. Using biomarkers as objective standards in the diagnosis of cervical biopsies. Am. J. Surg. Pathol. 2010; 34(8): 1077-87. https://dx.doi.org/10.1097/PAS.0b013e3181e8b2c4.
- Izadi-Mood N., Sarmadi S., Eftekhar Z., Jahanteegh H.A., Sanii S. Immunohistochemical expression of p16 and HPV L1 capsid proteins as predictive markers in cervical lesions. Arch. Gynecol. Obstet. 2014; 289(6): 1287-92. https://dx.doi.org/10.1007/s00404-013-3124-1.
- Yu L., Wang L., Zhong J., Chen S. Diagnostic value of p16INK4A, Ki-67, and human papillomavirus L1 capsid protein immunochemical staining on cell blocks from residual liquid-based gynecologic cytology specimens. Cancer Cytopathol. 2010; 118(1): 47-55. https://dx.doi.org/10.1002/cncy.20061.
- Doorbar J., Quint W., Banks L., Bravo I.G., Stoler M., Broker T.R. et al. The biology and life-cycle of human papillomaviruses. Vaccine. 2012; 30 Suppl 5: F55-70. https://dx.doi.org/10.1016/j.vaccine.2012.06.083.
- Sarmadi S., Izadi-mood N., Pourlashkari M., Yarandi F., Sanii S. HPV L1 capsid protein expression in squamous intraepithelial lesions of cervix uteri and its relevance to disease outcome. Arch. Gynecol. Obstet. 2012; 285(3): 779-84. https://dx.doi.org/10.1007/s00404-011-2010-y.
- Viveros-Carreño D., Fernandes A., Pareja R. Updates on cervical cancer prevention. Int. J. Gynecol. Cancer. 2023; 33(3): 394-402. https:// dx.doi.org/10.1136/ijgc-2022-003703.
- Byun S.W., Lee A., Kim S., Choi Y.J., Lee Y.S., Park J.S. Immunostaining of p16(INK4a)/Ki-67 and L1 capsid protein on liquid-based cytology specimens obtained from ASC-H and LSIL-H cases. Int J Med Sci. 2013; 10(12): 1602-7. https://dx.doi.org/10.7150/ijms.6526.
- Lee S.J., Lee A.W., Kim T.J., Kim J.H., Bae J.H., Lee C.W. et al. Correlation between immunocytochemistry of human papilloma virus L1 capsid protein and behavior of low-grade cervical cytology in Korean women. J. Obstet. Gynaecol. Res. 2011; 37(9): 1222-8. https://dx.doi.org/10.1111/j.1447-0756.2010.01506.x.
- Rauber D., Mehlhorn G., Fasching P.A., Beckmann M.W., Ackermann S. Prognostic significance of the detection of human papilloma virus L1 protein in smears of mild to moderate cervical intraepithelial lesions. Eur. J. Obstet. Gynecol. Reprod. Biol. 2008; 140(2): 258-62. https://dx.doi.org/10.1016/ j.ejogrb.2008.05.003.
- Xiao W., Bian M., Ma L., Liu J., Chen Y., Yang B. et al. Immunochemical analysis of human papillomavirus L1 capsid protein in liquid-based cytology samples from cervical lesions. Acta Cytol. 2010; 54(5): 661-7. https://dx.doi.org/10.1159/000325229.
Arquivos suplementares
