Publicado

2022-02-04

Análise histomorfométrica em lesões cervicais induzidas por HPV

Histomorphometric analysis in hpv-induced cervical lesions

Análisis histomorfométrico en lesiones cervicales inducidas por VPH

DOI:

https://doi.org/10.15446/rcciquifa.v50n3.85687

Palabras clave:

Linfócitos, células plasmocitárias, eosinófilos, câncer cervical (pt)
Linfocitos, células plasmocitarias, eosinófilos, cáncer de cuello uterino (es)
Lymphocytes, plasmocyte cells, eosinophils, cervical cancer (en)

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Autores/as

Introdução: Lesões intraepiteliais escamosas (SIL) do colo do útero envolvem alteração displásica ou maturação celular anormal e sua progressão pode resultar em carcinoma cervical. Alguns estudos relatam a importância do sistema imunológico no processo de progressão tumoral. Portanto, é importante caracterizar o infiltrado inflamatório como um possível marcador de prognóstico. Objetivo: analisar a densidade do infil-trado inflamatório em diferentes graus de SIL e no câncer cervical para compreender as alterações locais e sistêmicas nas interações entre as lesões cervicais associadas ao HPV e o sistema imunológico. Métodos: Cento e oito (108) espécimes de biópsia cervical foram obtidos de pacientes tratados no hospital terciário e foram estratificados em quatro grupos: Lesão intraepitelial escamosa de baixo grau (LSIL), Lesão intraepi-telial escamosa de alto grau (HSIL), câncer cervical (CC) e negativo para lesão intrae-pitelial e malignidade (NILM). A análise histomorfométrica foi realizada a partir da identificação e quantificação das células inflamatórias em dez (10) campos por amostra em imagens capturadas por um sistema digital e analisadas no software Leica Qwin Pro V 3.5.1, Leica Microsystems Ltd. As diferenças entre os grupos foram avaliadas por Anova seguida do teste de Tukey. Os testes com valores de p <0,05 foram conside-rados significativos. Resultados: encontramos um aumento significativo no número médio de linfócitos (células/mm² e células/campo) nas amostras de CC em relação aos demais grupos. Não foi observada diferença estatística em relação aos neutrófilos, plasmócitos e eosinófilos. Conclusão: as amostras de câncer cervical tinham significa-tivamente mais linfócitos do que NILM, ou LSIL e HSIL, sugerindo que este tipo de célula desempenha um papel central na imunidade celular contra o carcinoma cervical.

Introduction: squamous intraepithelial lesions (SIL) of the cervix involve dysplastic change, or abnormal cell maturation and their progression can result in cervical carcinoma. Some studies have reported the importance of the immune system in the process of tumor progression. Therefore, it is important to characterize the inflam-matory infiltration as a possible marker of prognosis. Aim: to analyze density of the inflammatory infiltrate in different degrees of SIL and in cervical cancer to under-stand local and systemic changes in the interactions between HPV associated cervical lesions and the immune system. Methods: one hundred and eight (108) cervical biopsy specimens were obtained from patients treated at the tertiary hospital and were stratified into four groups: Low-grade squamous intraepithelial lesion (LSIL), High-grade squamous intraepithelial lesion (HSIL), cervical cancer (CC) and nega-tive for intraepithelial lesion and malignancy (NILM). Histomorphometric analysis was performed from the identification and quantification of inflammatory cells in ten (10) fields per sample in images captured by a digital system and analyzed using the software Leica Qwin Pro V 3.5.1, Leica Microsystems Ltd. Differences between groups were evaluated by Anova followed by Tukey test. Tests yielding p values < 0.05 were considered significant. Results: we found a significant increase in the average number of lymphocytes (cells/mm² and cells/field) in samples of CC in relation to the other groups. No statistical difference was observed in relation to neutrophils, plasma cells and eosinophils. Conclusion: cervical cancer specimens had significantly more lymphocytes than NILM, or LSIL and HSIL, suggesting that this cell type plays a central role in cellular immunity against cervical carcinoma.

Introducción: las lesiones escamosas intraepiteliales (SIL) del cuello uterino implican cambios displásicos o maduración celular anormal y su progresión puede resultar en carcinoma cervical. Algunos estudios han informado de la importancia del sistema inmunológico en el proceso de progresión tumoral. Por tanto, es impor-tante caracterizar la infiltración inflamatoria como un posible marcador de pronós-tico. Objetivo: analizar la densidad del infiltrado inflamatorio en diferentes grados de SIL y en cáncer de cuello uterino para comprender los cambios locales y sistémicos en las interacciones entre las lesiones cervicales asociadas al VPH y el sistema inmu-nológico. Métodos: se obtuvieron ciento ocho (108) muestras de biopsia cervical de pacientes tratados en el hospital terciario y se estratificaron en cuatro grupos: Lesión intraepitelial escamosa de bajo grado (LSIL), Lesión intraepitelial escamosa de alto grado (HSIL), cáncer de cuello uterino (CC) y negativo para lesiones intraepiteliales y malignidad (NILM). El análisis histomorfométrico se realizó a partir de la iden-tificación y cuantificación de células inflamatorias en diez (10) campos por muestra en imágenes capturadas por un sistema digital y analizadas utilizando el software Leica Qwin Pro-V 3.5.1, Leica Microsystems Ltd. Anova seguido de la prueba de Tukey. Las pruebas que arrojaron valores de p <0,05 se consideraron significativas. Resultados: encontramos un aumento significativo en el número medio de linfo-citos (células/mm² y células/campo) en muestras de CC en relación con los otros grupos. No se observó diferencia estadística en relación con neutrófilos, células plas-máticas y eosinófilos. Conclusión:las muestras de cáncer de cuello uterino tenían significativamente más linfocitos que NILM o LSIL y HSIL, lo que sugiere que este tipo de células juega un papel central en la inmunidad celular contra el carcinoma de cuello uterino.

Referencias

Y. Chen, H. Wang, W. Lin, P. Shuai, ADAR1 overexpression is associated with cervical cancer progression and angiogenesis, Diagn. Pathol., 12(1), 12 (2017). DOI: https://doi.org/10.1186/s13000-017-0600-0

K.S. Tewari, B.J. Monk, New strategies in advanced cervical cancer: from angio-genesis blockade to immunotherapy, Clin. Cancer Res.,20(21), 5349-5358 (2014). DOI: https://doi.org/10.1158/1078-0432.CCR-14-1099

N.S.L. Yeo-Teh, Y. Ito, S. Jha, High-risk human papillomaviral oncogenes E6 and E7 target key cellular pathways to achieve oncogenesis, Int. J. Mol. Sci., 19(6), E1706 (2018). DOI: https://doi.org/10.3390/ijms19061706

R.F.A. Costa, A. Longatto-Filho, F. de Lima-Vazquez, C. Pinheiro, L.C. Zefer-ino, J.H.T.G. Fregnani, Trend analysis of the quality indicators for the Brazilian cervical cancer screening programme by region and state from 2006 to 2013, BMC Cancer, 18(1), 126 (2018). DOI: https://doi.org/10.1186/s12885-018-4047-9

INCA, Instituto Nacional de Câncer José Alencar Gomes da Silva, Estimativa 2018: incidência de câncer no Brasil, Coordenação de Prevenção e Vigilância. – Rio de Janeiro, 2017.

A. Pańczyszyn, E. Boniewska-Bernacka, G. Głąb, Telomeres and telomerase during human papillomavirus-induced carcinogenesis, Mol. Diagn. Ther., 22(4), 421-430 (2018). DOI: https://doi.org/10.1007/s40291-018-0336-x

Y.Q. Wang, J.L. Lu, Y.R. Liang, Q.S. Li, Suppressive effects of EGCG on cervical cancer, Molecules, 23(9), E2334 (2018). DOI: https://doi.org/10.3390/molecules23092334

S. Rashid, S. Labani, B.C. Das, Knowledge, awareness and attitude on HPV, HPV vaccine and cervical cancer among the college students in India, PLoS One, 11(11), e0166713 (2016). DOI: https://doi.org/10.1371/journal.pone.0166713

A.P. Ferreira-Costa, A.K. Gonçalves, P.R.L. Machado, L.B.C. Souza, A. Sarmento, R.N.O. Cobucci, P.C. Giraldo, S.S. Witkin, Immune response to human papillomavirus one year after prophylactic vaccination with AS04-adjuvanted HPV-16/18 vaccine: HPV-specific IgG and IgA antibodies in the circulation and the cervix, Asian Pac. J. Cancer Prev., 19(8), 2313-2317 (2018).

A. Albawardi, M.R. Quddus, S. Al Awar, S. Almarzooqi, Frequency of rare and multi viral high-risk HPV types of infection in cervical high grade squamous intraepithelial lesions in a non-native dominant Middle Eastern country: a poly-merase chain reaction-based pilot study, Diagn. Pathol., 13, 42 (2018). DOI: https://doi.org/10.1186/s13000-018-0716-x

X. Wang, X. Huang, Y. Zhang, Involvement of human papillomaviruses in cervi-cal cancer, Front. Microbiol., 9, 2896 (2018). DOI: https://doi.org/10.3389/fmicb.2018.02896

L. Yao, M. Yuan, J. Yuan, P. Zhou, L. Mei, J. Cheng, Analysis of cervical human papillomavirus infection in 2300 women in Urumqi, China, Medicine (Balti-more), 97(45), e13206 (2018). DOI: https://doi.org/10.1097/MD.0000000000013206

J. Zhang, C. Burn, K. Young, M. Wilson, K. Ly, M. Budhwani, A. Tschirley, A. Braithwaite, M. Baird, M. Hibma, Microparticles produced by human papillo-mavirus type 16 E7-expressing cells impair antigen presenting cell function and the cytotoxic T cell response, Sci. Rep., 8(1), 2373 (2018) . DOI: https://doi.org/10.1038/s41598-018-20779-2

A.A. Bashaw, G.R. Leggatt, J. Chandra, Z.K. Tuong, I.H. Frazer, Modulation of antigen presenting cell functions during chronic HPV infection, Papillomavirus Res., 4, 58-65 (2017). DOI: https://doi.org/10.1016/j.pvr.2017.08.002

A. Lechner, H. Schlößer, S.I. Rothschild, M. Thelen, S. Reuter, Zentis P, et al., Characterization of tumor-associated T-lymphocyte subsets and immune check-point molecules in head and neck squamous cell carcinoma, Oncotarget, 8(27), 44418-44433 (2017). DOI: https://doi.org/10.18632/oncotarget.17901

E. Ancuta, S. Buţureanu, F. Zugun-Eloae, C.R. Anton, C. Ancuta, D. Diţescu, E. Anton, Potential value of in situ cellular immune response in HPV subtype 16 and 18 positive cervical cancer, Rom. J. Morphol. Embryol., 55(3), 817-822 (2014).

J.P.P. Alve, T.A.A. de Medeiros-Fernandes, J.M.G. de Araújo, R.N.O. Cobucci, D.C.F. Lanza, F.L. Bezerra, V.S. Andrade, J.V. Fernandes, Th17 response in patients with cervical cancer, Oncol Lett., 16(5), 6215-6227 (2018). DOI: https://doi.org/10.3892/ol.2018.9481

S. Smola, Immunopathogenesis of HPV-associated cancers and prospects for immunotherapy, Viruses, 9(9), E254 (2017). DOI: https://doi.org/10.3390/v9090254

R.R. Zheng, M. Huang, C. Jin, H.C. Wang, J.T. Yu, L.C. Zeng, F.Y. Zheng, F. Lin, Cervical cancer systemic inflammation score: a novel predictor of progno-sis, Oncotarget, 7(12), 15230-15242 (2016). DOI: https://doi.org/10.18632/oncotarget.7378

B. Bojaxhiu, A.J. Templeton, O. Elicin, M. Shelan, K. Zaugg, M. Walser, R. Giger, D.M. Aebersold, A. Dal-Pra, Relation of baseline neutrophil-to-lympho-cyte ratio to survival and toxicity in head and neck cancer patients treated with (chemo-) radiation, Radiat. Oncol., 13(1), 216 (2018). DOI: https://doi.org/10.1186/s13014-018-1159-y

T. Schweiger, A.S. Berghoff, C. Glogner, O. Glueck, O. Rajky, D. Traxler, P. Birner, M. Preusser, W. Klepetko, K. Hoetzenecker, Tumor-infiltrating lympho-cyte subsets and tertiary lymphoid structures in pulmonary metastases from colorectal cancer, Clin. Exp. Metastasis, 33(7), 727-739 (2016). DOI: https://doi.org/10.1007/s10585-016-9813-y

Q.T. Huang, Q.Q. Man, J. Hu, Y.L. Yang, Y.M. Zhang, W. Wang, M. Zhong, Y.H. Yu, Prognostic significance of neutrophil-to-lymphocyte ratio in cervical cancer: A systematic review and meta-analysis of observational studies, Oncotar-get, 8(10), 16755-16764 (2017). DOI: https://doi.org/10.18632/oncotarget.15157

F. Noble, T. Mellows, L.H. McCormick-Matthews, A.C. Bateman, S. Harris, T.J. Underwood, et al., Tumour infiltrating lymphocytes correlate with improved survival in patients with oesophageal adenocarcinoma, Cancer Immunol. Immu-n o t h e r., 65(6), 651-662 (2016). DOI: https://doi.org/10.1007/s00262-016-1826-5

J. Lu, X.M. Chen, H.R. Huang, F.P. Zhao, F. Wang, X. Liu, X.P. Li, Detai-led analysis of inflammatory cell infiltration and the prognostic impact on nasopharyngeal carcinoma, Head Neck, 40(6), 1245-1253 (2018). DOI: https://doi.org/10.1002/hed.25104

M.Z. Wu, W.N. Li, N. Cha, L.X. Tian, Y.I. Zhang, X. Wu, K.J. Guo, G.P. Wu, Diagnostic utility of HPV16 E6 mRNA or E7 mRNA quantitative expression for cervical cells of patients with dysplasia and carcinoma, Cell Transplant., 27(9), 1401-1406 (2018). DOI: https://doi.org/10.1177/0963689718788521

S. Chun, K. Shin, K.H. Kim, H.Y. Kim, W. Eo, J.Y. Lee, J. Namkung, S.H. Kwon, S.B. Koh, H.B. Kim, The neutrophil-lymphocyte ratio predicts recurrence of cervical intraepithelial neoplasia, J. Cancer, 8(12), 2205-2211 (2017). DOI: https://doi.org/10.7150/jca.19173

V. Kaya, M. Yıldırım, G. Yazıcı, A.Y. Yalçın, N. Orhan, A. Güzel, Prognostic significance of indicators of systemic inflammatory responses in glioblastoma patients, Asian Pac. J. Cancer Prev., 18(12), 3287-3291 (2017).

Y. Liang, W. Lü, X. Zhang, B. Lü, Tumor-infiltrating CD8+ and FOXP3+ lym-phocytes before and after neoadjuvant chemotherapy in cervical cancer, Diagn. Pathol., 13(1), 93 (2018). DOI: https://doi.org/10.1186/s13000-018-0770-4

D. Das, B. Sarkar, S. Mukhopadhyay, C. Banerjee, S. Biswas-Mondal, An altered ratio of CD4+ and CD8+ T lymphocytes in cervical cancer tissues and periphe-ral blood – A prognostic clue? Asian Pac. J. Cancer Prev., 19(2), 471-478 (2018).

W.C. Chang, C.H. Li, L.H. Chu, P.S. Huang, B.C. Sheu, S.C. Huang, Regula-tory T cells suppress natural killer cell immunity in patients with human cervical carcinoma, Int. J. Gynecol. Cancer, 26(1), 156-162 (2016). DOI: https://doi.org/10.1097/IGC.0000000000000578

A.K. Mishra, T. Kadoishi, X. Wang, E. Driver, Z. Chen, X.J. Wang, J.H. Wang, Squamous cell carcinomas escape immune surveillance via inducing chronic acti-vation and exhaustion of CD8+ T Cells co-expressing PD-1 and LAG-3 inhibi-tory receptors, Oncotarget, 7(49), 81341-81356 (2016). DOI: https://doi.org/10.18632/oncotarget.13228

C.S. Silva, M.A. Michelin, R.M. Etchebehere, S.J. Adad, E.F. Murta, Local lympho-cytes and nitric oxide synthase in the uterine cervical stroma of patients with grade III cervical intraepithelial neoplasia, Clinics (Sao Paulo), 65(6), 575-581 (2010).

F. Xie, L.B. Liu, W.Q. Shang, K.K. Chang, Y.H. Meng, J. Mei, J.J. Yu, D.J. Li, M.Q. Li, The infiltration and functional regulation of eosinophils induced by TSLP promote the proliferation of cervical cancer cell, Cancer Lett., 364(2):106-117 (2015). DOI: https://doi.org/10.1016/j.canlet.2015.04.029

G. Varricchi, M.R. Galdiero, S. Loffredo, V. Lucarini, G. Marone, F. Mattei, G. Marone, G. Schiavoni, Eosinophils: The unsung heroes in cancer? Oncoimmuno-log y, 7(2), e1393134 (2017). DOI: https://doi.org/10.1080/2162402X.2017.1393134

K. Holub, A. Biete, Impact of systemic inflammation biomarkers on the survival outcomes of cervical cancer patients, Clin. Transl. Oncol., 21, 836-844 (2019). DOI: https://doi.org/10.1007/s12094-018-1991-4

G.W. Spiegel, M. Ashraf, J.J. Brooks, Eosinophils as a marker for invasion in cer-vical squamous neoplastic lesions, Int. J. Gynecol. Pathol., 21(2), 117-124 (2002). DOI: https://doi.org/10.1097/00004347-200204000-00003

W.J. Van Driel, P.C. Hogendoorn, F.W. Jansen, A.H. Zwinderman, J.B. Trimbos, G.J. Fleuren, Tumor-associated eosinophilic infiltrate of cervical cancer is indi-cative for a less effective immune response, Hum. Pathol., 27(9), 904-911 (1996). DOI: https://doi.org/10.1016/S0046-8177(96)90216-6

W.J. Van Driel, P. Kievit-Tyson, L.C. van den Broek, A.H. Zwinderman, B.J. Trimbos, G.J. Fleuren, Presence of an eosinophilic infiltrate in cervical squamous carcinoma results from a type 2 immune response, Gynecol. Oncol., 74(2), 188-195 (1999). DOI: https://doi.org/10.1006/gyno.1999.5431

Cómo citar

APA

Oliveira, E. B., de Carvalho, K. T. C., Cobucci, R. N. O., Gonçalves, A. K., Dantas, D. de S. y Crispim, J. C. de O. (2022). Análise histomorfométrica em lesões cervicais induzidas por HPV. Revista Colombiana de Ciencias Químico-Farmacéuticas, 50(3). https://doi.org/10.15446/rcciquifa.v50n3.85687

ACM

[1]
Oliveira, E.B., de Carvalho, K.T.C., Cobucci, R.N.O., Gonçalves, A.K., Dantas, D. de S. y Crispim, J.C. de O. 2022. Análise histomorfométrica em lesões cervicais induzidas por HPV. Revista Colombiana de Ciencias Químico-Farmacéuticas. 50, 3 (feb. 2022). DOI:https://doi.org/10.15446/rcciquifa.v50n3.85687.

ACS

(1)
Oliveira, E. B.; de Carvalho, K. T. C.; Cobucci, R. N. O.; Gonçalves, A. K.; Dantas, D. de S.; Crispim, J. C. de O. Análise histomorfométrica em lesões cervicais induzidas por HPV. Rev. Colomb. Cienc. Quím. Farm. 2022, 50.

ABNT

OLIVEIRA, E. B.; DE CARVALHO, K. T. C.; COBUCCI, R. N. O.; GONÇALVES, A. K.; DANTAS, D. de S.; CRISPIM, J. C. de O. Análise histomorfométrica em lesões cervicais induzidas por HPV. Revista Colombiana de Ciencias Químico-Farmacéuticas, [S. l.], v. 50, n. 3, 2022. DOI: 10.15446/rcciquifa.v50n3.85687. Disponível em: https://revistas.unal.edu.co/index.php/rccquifa/article/view/85687. Acesso em: 10 jul. 2024.

Chicago

Oliveira, Emanuelly Bernardes, Kleyton Thiago Costa de Carvalho, Ricardo Ney Oliveira Cobucci, Ana Katherine Gonçalves, Deyse de Souza Dantas, y Janaína Cristiana de Oliveira Crispim. 2022. «Análise histomorfométrica em lesões cervicais induzidas por HPV». Revista Colombiana De Ciencias Químico-Farmacéuticas 50 (3). https://doi.org/10.15446/rcciquifa.v50n3.85687.

Harvard

Oliveira, E. B., de Carvalho, K. T. C., Cobucci, R. N. O., Gonçalves, A. K., Dantas, D. de S. y Crispim, J. C. de O. (2022) «Análise histomorfométrica em lesões cervicais induzidas por HPV», Revista Colombiana de Ciencias Químico-Farmacéuticas, 50(3). doi: 10.15446/rcciquifa.v50n3.85687.

IEEE

[1]
E. B. Oliveira, K. T. C. de Carvalho, R. N. O. Cobucci, A. K. Gonçalves, D. de S. Dantas, y J. C. de O. Crispim, «Análise histomorfométrica em lesões cervicais induzidas por HPV», Rev. Colomb. Cienc. Quím. Farm., vol. 50, n.º 3, feb. 2022.

MLA

Oliveira, E. B., K. T. C. de Carvalho, R. N. O. Cobucci, A. K. Gonçalves, D. de S. Dantas, y J. C. de O. Crispim. «Análise histomorfométrica em lesões cervicais induzidas por HPV». Revista Colombiana de Ciencias Químico-Farmacéuticas, vol. 50, n.º 3, febrero de 2022, doi:10.15446/rcciquifa.v50n3.85687.

Turabian

Oliveira, Emanuelly Bernardes, Kleyton Thiago Costa de Carvalho, Ricardo Ney Oliveira Cobucci, Ana Katherine Gonçalves, Deyse de Souza Dantas, y Janaína Cristiana de Oliveira Crispim. «Análise histomorfométrica em lesões cervicais induzidas por HPV». Revista Colombiana de Ciencias Químico-Farmacéuticas 50, no. 3 (febrero 4, 2022). Accedido julio 10, 2024. https://revistas.unal.edu.co/index.php/rccquifa/article/view/85687.

Vancouver

1.
Oliveira EB, de Carvalho KTC, Cobucci RNO, Gonçalves AK, Dantas D de S, Crispim JC de O. Análise histomorfométrica em lesões cervicais induzidas por HPV. Rev. Colomb. Cienc. Quím. Farm. [Internet]. 4 de febrero de 2022 [citado 10 de julio de 2024];50(3). Disponible en: https://revistas.unal.edu.co/index.php/rccquifa/article/view/85687

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