O valor da superexpressão do p16 nas lesões precursoras do câncer de colo uterino em mulheres privadas de liberdade
DOI:
https://doi.org/10.34119/bjhrv6n2-171Keywords:
HPV, câncer de colo do útero, imunocitoquímicaAbstract
A infecção genital por HPVs de alto risco (HR-HPV) oncogênicos é fator de risco importante ao desenvolvimento do câncer de colo de útero. A partir da detecção do vírus por exames de rastreio e investigação de biomarcadores imuno-histoquímicos de alteração do ciclo celular, como proteína p16INK4a, possibilita-se melhor reprodutibilidade diagnóstica e condução terapêutica. As mulheres privadas de liberdade apresentam significativa incidência de infecção por HPV, sendo a utilização dos biomarcadores possível ferramenta de triagem para melhor diagnóstico, ao ser observada a quantificação de alteração a nível celular e, a partir desses valores, ser realizada associação a demais apresentações clínicas. Objetivo: Visa-se associar os resultados da detecção de HPV de alto risco em mulheres privadas de liberdade com a superexpressão do marcador proteína p16INK4a observada através dos exames imunocitoquímicos. Métodos: Estudo observacional, transversal, descritivo, analítico e epidemiológico de prevalência do diagnóstico de infecção por HPV, do qual participaram 268 Mulheres Privadas de Liberdade (MPL) no estado do Amazonas (AM), que foram submetidas à autocoleta utilizando o dispositivo Coari® e Teste Cobas® 4800 HPV CTNG (Roche®). As pacientes com resultado HPV positivo foram submetidas à colpocitologia em meio líquido, colposcopia, avaliação da imunocitoquímica através da proteína p16INK4a e biópsia, quando indicado. Resultados: Das 268 mulheres avaliadas, a idade variou de 19 a 64 anos (média ± desvio padrão: 33,5 ± 9,1 anos). O HPV foi detectado em 66 (24,6%) das mulheres. Duas mulheres apresentaram lesão de alto grau e 13 de baixo grau, no histopatológico. Oito mulheres apresentaram alteração na colpocitologia e 32 (64%) na superexpressão da proteína p16INK4a. Conclusão: A prevalência de HPV na MPL foi elevada e que essa população carcerária apresenta características peculiares com maior prevalência de outros tipos de HPV de alto. A superexpressão p16INK4a foi positiva – demonstrando dados inéditos na população carcerária –, porém, apresenta limitações dos resultados e, consequentemente, do seu uso isoladamente.
References
Instituto Nacional de Câncer [Internet].; 2018 Feb 5[cited 2021 Apr 13].Available from: https://www.inca.gov.br/imprensa/inca-estima-que-havera-cerca-de-600-mil-casos-novos-de-cancer-em-2018
Instituto Nacional de Câncer [Internet].; 2019 [cited 2021 Mar 29]. Available from: https://www.inca.gov.br/MortalidadeWeb/pages/Modelo03/consultar.xhtml;jsessionid=986238F918FEB56989EFDCD86B0ED730#panelResultado
– IARC. IARC Handbooks of Cancer Prevention. Volume 10: cervix cancer screening [E-book on the Internet]. Lyon: IARC Press, International Agency for Research on Cancer; 2005 [cited 2021 Apr 13]. 313p. Available from: https://publications.iarc.fr/Book-And-Report-Series/Iarc-Handbooks-Of-Cancer-Prevention/Cervix-Cancer-Screening-2005
Lorenzi AT, Syrjänen KJ, Longatto-Filho A. Human papillomavirus (HPV) screening and cervical cancer burden. A Brazilian perspective. Virol J [Internet]. 2015 Jul 25 [cited 2021 Apr 14];12:112. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514998/ doi: 10.1186/s12985-015-0342-0. PMID: 26208521; PMCID: PMC4514998.
Pimple S, Mishra G, Shastri S. Global strategies for cervical cancer prevention. Curr Opin Obstet Gynecol [Internet]. 2016 Feb [cited 2021 Apr 12];28(1):4-10. Available from: https://pubmed.ncbi.nlm.nih.gov/26642063/. doi: 10.1097/GCO.0000000000000241. PMID: 26642063.
Lessa PRA, Ribeiro SG, Lima DJM, Nicolau AIO, Damasceno AKC, Pinheiro AKB. Presença de lesões intraepiteliais de alto grau entre Mulheres Privadas de Liberdade: estudo documental. Rev Lat Am Enfermagem. 2012;20(2):1-9. doi: 10.1590/S0104-11692012000200019.
Smith, R.A., Andrews, K.S., Brooks, D., Fedewa, S.A., Manassaram‐Baptiste, D., Saslow, D. and Wender, R.C. Cancer screening in the United States, 2019: A review of current American Cancer Society guidelines and current issues in cancer screening [Internet]. 2019 [cited 2021 Apr 13];CA A Cancer J Clin, 69: 184-210. Available from: https://doi.org/10.3322/caac.21557
Jeronimo J, Castle PE, Temin S, Denny L, Gupta V, Kim JJ, Luciani S, Murokora D, Ngoma T, Qiao Y, Quinn M, Sankaranarayanan R, Sasieni P, Schmeler KM, Shastri SS. Secondary Prevention of Cervical Cancer: ASCO Resource-Stratified Clinical Practice Guideline. J Glob Oncol [Internet]. 2016 Oct 12 [cited 2021 Apr 13];3(5):635-657. Available from: https://pubmed.ncbi.nlm.nih.gov/29094101/ doi: 10.1200/JGO.2016.006577. PMID: 29094101; PMCID: PMC5646891.
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin [Internet]. 2021 Jan [cited 2021 Apr 14];71(1):7-33. Available from: https://pubmed.ncbi.nlm.nih.gov/33433946/ doi: 10.3322/caac.21654. Epub 2021 Jan 12. PMID: 33433946.
Youssef MA, Abdelsalam L, Harfoush RA, Talaat IM, Elkattan E, Mohey A, Abdella RM, Farhan MS, Foad HA, Elsayed AM, Elkinaai NA, Ghaith D, Rashed ME, Ghafar MA, Khamis Y, Hosni AN. Prevalence of human papilloma virus (HPV) and its genotypes in cervical specimens of Egyptian women by linear array HPV genotyping test. Infect Agent Cancer [Internet]. 2016 Feb 17 [cited 2021 Apr 13];11:6. Available from: https://pubmed.ncbi.nlm.nih.gov/26889206/ doi: 10.1186/s13027-016-0053-1. PMID: 26889206; PMCID: PMC4756400.
Modibbo F, Iregbu KC, Okuma J, Leeman A, Kasius A, de Koning M, Quint W, Adebamowo C. Randomized trial evaluating self-sampling for HPV DNA based tests for cervical cancer screening in Nigeria. Infect Agent Cancer [Internet]. 2017 Feb 6 [cited 2021 Apr 13];12:11. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294803/ doi: 10.1186/s13027-017-0123-z. PMID: 28184239; PMCID: PMC5294803.
Yeh PT, Kennedy CE, de Vuyst H et al. Self-sampling for human papillomavirus (HPV) testing: a systematic review and meta-analysis. BMJ Global Health [Internet]. 2019 [cited 2021 Apr 13];4:e001351. Available from: https://gh.bmj.com/content/4/3/e001351.citation-tools doi:10.1136/ bmjgh-2018-001351
Hillemanns P, Soergel P, Hertel H, Jentschke M. Epidemiology and Early Detection of Cervical Cancer. Oncol Res Treat [Internet]. 2016 [cited 2020 Apr 13];39(9):501-6. Available from: https://pubmed.ncbi.nlm.nih.gov/27614953/ doi: 10.1159/000448385. Epub 2016 Aug 22. PMID: 27614953.
Wong EL, Chan PK, Chor JS, Cheung AW, Huang F, Wong SY. Evaluation of the Impact of Human Papillomavirus DNA Self-sampling on the Uptake of Cervical Cancer Screening. Cancer Nurs [Internet]. 2016 Jan-Feb [cited 2021 Apr 13];39(1):E1-E11. Available from: https://pubmed.ncbi.nlm.nih.gov/25730587/ doi: 10.1097/NCC.0000000000000241. PMID: 25730587; PMCID: PMC4892762.
Sawaya GF, Smith-McCune K, Kuppermann M. Cervical Cancer Screening: More Choices in 2019. JAMA [Internet]. 2019 May 28 [cited 2021 Apr 13];321(20):2018-2019. Available from: https://pubmed.ncbi.nlm.nih.gov/31135834/ doi: 10.1001/jama.2019.4595. PMID: 31135834; PMCID: PMC6656358.
Torres KL, Mariño JM, Pires Rocha DA, de Mello MB, de Melo Farah HH, Reis RDS, Alves VDCR, Gomes E, Martins TR, Soares AC, de Oliveira CM, Levi JE. Self-sampling coupled to the detection of HPV 16 and 18 E6 protein: A promising option for detection of cervical malignancies in remote areas. PLoS One [Internet]. 2018 Jul 23;13(7):e0201262. Available from: https://pubmed.ncbi.nlm.nih.gov/30036381/ doi: 10.1371/journal.pone.0201262. PMID: 30036381; PMCID: PMC6056043.
Ebisch, R., van der Horst, J., Hermsen, M. et al. Evaluation of p16/Ki-67 dual-stained cytology as triage test for high-risk human papillomavirus-positive women. Mod Pathol 30 [Internet]. 2017 Mar 17 [cited 2021 Apr 15];1021–1031. Available from: https://www.nature.com/articles/modpathol201716#citeas doi: https://doi.org/10.1038/modpathol.2017.16
Tjalma WAA. Diagnostic performance of dual-staining cytology for cervical cancer screening: A systematic literature review. Eur J Obstet Gynecol Reprod Biol [Internet]. 2017 Mar [cited 2021 Apr 13];210:275-280. doi: 10.1016/j.ejogrb.2017.01.009. Epub 2017 Jan 8. PMID: 28086168.
Bergeron C, Ronco G, Reuschenbach M, Wentzensen N, Arbyn M, Stoler M, von Knebel Doeberitz M. The clinical impact of using p16(INK4a) immunochemistry in cervical histopathology and cytology: an update of recent developments. Int J Cancer [Internet]. 2015 Jun 15 [cited 2021 Apr 12];136(12):2741-51. Available from: https://pubmed.ncbi.nlm.nih.gov/24740700/ doi: 10.1002/ijc.28900.
Verma L, Shamsunder S, Malik S, Arora R. To Evaluate the Role of p16Ink4a Immunocytochemistry for Detection of CIN2+ in Women Detected Screen Positive by Visual Inspection Using Acetic Acid. J Cytol [Internet]. 2020 Apr-Jun [cited 2021 Apr 12];37(2):82-86. Available from: https://pubmed.ncbi.nlm.nih.gov/32606495/ doi: 10.4103/JOC.JOC_89_18. Epub 2020 Apr 14. PMID: 32606495; PMCID: PMC7315916.
Liao GD, Sellors JW, Sun HK, Zhang X, Bao YP, Jeronimo J, Chen W, Zhao FH, Song Y, Cao Z, Zhang SK, Xi MR, Qiao YL. p16INK4A immunohistochemical staining and predictive value for progression of cervical intraepithelial neoplasia grade 1: a prospective study in China. Int J Cancer [Internet]. 2014 Apr 1 [cited 2021 Apr 13];134(7):1715-24. Available from: https://pubmed.ncbi.nlm.nih.gov/24105727/ doi: 10.1002/ijc.28485. Epub 2013 Oct 12. PMID: 24105727.
Nichiata L, Martins N, Viana L, Torres A, Silva G, Oliva N, et al. Prevalência de Infecções Sexualmente Transmissíveis em Mulheres Privadas de Liberdade. Rev Saúde. 2019;45(1):1-10. doi: https://doi.org/10.5902/2236583431848.
Darragh TM, Colgan TJ, Cox JT, Heller DS, Henry MR, Luff RD, et al. The lower anogenital squamous terminology standardization project for HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. J Low Genit Tract Dis. 2012;16(3):205-42. doi: 10.1097/LGT.0b013e31825c31dd.
Pinto AP, Crum CP, Hirsch MS. Molecular markers of early cervical neoplasia. Diagn Histopathol. 2010;16(10):445-54. doi: 10.1016/j.mpdhp.2010.06.012.
Instituto Nacional de Câncer José Alencar Gomes da Silva. Nomenclatura brasileira para laudos citopatológicos cervicais [Internet]. 3a ed. Rio de Janeiro: INCA; 2012 [citado 18 Out 2021]. Disponível em: https://www.inca.gov.br/publicacoes/livros/nomenclatura-brasileira-para-laudos-citopatologicos-cervicais.
R Core Team. R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2019.
Shapiro SS, Wilk MB. An analysis of variance test for normality (complete samples). Biometrika. 1965;3-4:591.
Montgomery DC. Design and analysis of experiments. 8th ed. Hoboken: John Wiley & Sons; 2012.
Martins DC, Pesce GB, Silva GM, Fernandes CAM. Comportamento sexual e Infecções Sexualmente Transmissíveis em mulheres de apenados. Rev Lat Am Enfermagem. 2018;26:e3043. doi: 10.1590/1518-8345.2568.3043.
Silva ERP, Souza AS, Souza TGB, Tsuha DH, Barbieri AR. Screening for cervical cancer in imprisoned women in Brazil. PLoS ONE. 2017;12(12):e0187873. doi: 10.1371/journal.pone.0187873.
Souza CM, Silva LR, Pessoni GC, Silva LD, Carneiro MAS, Santos SHR, et al. Alterações celulares em exame colpocitológico de reeducandas do complexo prisional da Região Metropolitana de Goiânia. DST J Bras Doenças Sex Transm. 2011;23(1):12-5. doi: 10.5533/2177-8264-201123104.
Barbosa JAG, Freitas MIF. Vulnerability of women with mental disorders to Sexually Transmitted Infections (STIS) and HIV/AIDS. REME Rev Min Enferm [Internet]. 2011 [cited 2021 Out 18];15(2):217-24. Available from: http://bases.bireme.br/cgi-bin/wxislind.exe/iah/online/?IsisScript=iah/iah.xis&src=google&base=ADOLEC&lang=p&nextAction=lnk&exprSearch=600173&indexSearch=ID. doi: 600173.10.
Hashiguchi M, Nakao Y, Honda A, Kawaguchi A, Hanashima K, Nishiyama S, et al. What has changed since the introduction of Human Papillomavirus testing with the cytology-based cervical cancer screening system in Japan a social experiment. Acta Cytol. 2019;63(5):385-90. doi: 10.1159/000500190.
Fonseca AJ, Taeko D, Chaves TA, Amorim LDC, Murari RSW, Miranda AE. HPV infection and cervical screening in socially isolated indigenous women inhabitans of the amazonian rainforest. PLoS ONE. 2015;10(7):e0133635. doi: 10.1371/journal.pone.0133635.
Chen K, Ouyang Y, Hillemanns P, Jentshke M. Excellent analytical and clinical performance of a dry self-sampling device for Human Papillomavirus detection in an urban Chinese referral population. J Obstet Gynaecol Res. 2016;42(12):1839-45. doi: 10.1111/jog.13132.
Darlin L, Borgfeldt C, Forslund O, Hénic E, Dillner J, Kannisto P. Vaginal self-sampling without preservative for Human Papillomavirus testing shows good sensitivity. J Clin Virol. 2013;56(1):52-6. doi: 10.1016/j.jcv.2012.09.002.
Sena AB. Análise do desempenho de tecnologias alternativas para rastreio de lesões precursoras e de câncer invasivo de colo de útero [dissertação]. Manaus: Universidade Federal do Amazonas; 2019.
Lobo LMGA, Almeida MM, Oliveira FBM. Uterine column cancer, HPV and Papanicolaou experiment: a reflection on women's knowledge. ReonFacema. 2018;4(1):889-95.
Prigenzi KCK, Heinke T, Salim RC, Focchi GRA. Dual p16 and Ki-67 expression in liquid-based cervical cytological samples compared to pap cytology findings, biopsies, and HPV testing in cervical cancer screening: a diagnostic accuracy study. Acta Cytol. 2018;62(2):104-14. doi: 10.1159/000487504.
Wu J, Li XJ, Zhu W, Liu XP. Detection and pathological value of papillomavirus DNA and p16INK4A and p53 protein expression in cervical intraepithelial neoplasia. Oncol Lett. 2014;7(3):738-44. doi: 10.3892/ol.2014.1791.
Vasconcelos CTM, Coelho CF, Cunha DFF, Aquino OS, Anjos SJSB, Pinheiro AKB. Prevenção do câncer de colo uterino: o presídio como um espaço promotor de saúde. Rev Gest Saúde [Internet]. 2013 [citado 18 Out 2021];4(3):972-84. Disponível em: http://www.repositorio.ufc.br/handle/riufc/6760.
Kisser A, Zechmeister-Koss I. A systematic review of p16/Ki-67 immuno-testing for triage of low grade cervical cytology. BJOG. 2015;122(1):64-70. doi: 10.1111/1471-0528.13076.
Lewitowicz P, Nasierowska-Guttmejer A, Rokita W, Adamczyk-Gruszka O, Gluszek S, Chrapek M, et al. HPV genotyping and p16/Ki-67 test significantly improve detection rate of high-grade cervical squamous intraepithelial lesion. Arch Med Sci. 2019;16(1):87-93. doi: 10.5114/aoms.2018.80697.
Baros A, Badea M, Bohiltea R, Cirstoiu M. New molecular markers for cervical precancer detection optimization. immunocytochemistry test: p16/ki67 dual staining (CINtec PLUS test). Gineco.eu. 2016;(12)180-2. doi: 10.18643/gieu.2016.180.
Bergeron C, Ronco G, Reuschenbach M, Wentzensen N, Arbyn M, Stoler M, et al. The clinical impact of using p16(INK4a) immunochemistry in cervical histopathology and cytology: an update of recent developments. Int J Cancer. 2015;136(12):2741-51. doi: 10.1002/ijc.28900.
Tsoumpou I, Arbyn M, Kyrgiou M, Wentzensen N, Koliopoulos G, Martin-Hirsch P, et al. p16(INK4a) immunostaining in cytological and histological specimens from the uterine cervix: a systematic review and meta-analysis. Cancer Treat Rev. 2009;35(3):210-20. doi: 10.1016/j.ctrv.2008.10.005.
Mustafa RA, Santesso N, Khatib R, Mustafa AA, Wiercioch W, Kehar R, et al. Systematic reviews and meta-analyses of the accuracy of HPV tests, visual inspection with acetic acid, cytology, and colposcopy. Int J Gynecol Obstet. 2016;132(3):259-65. doi: 10.1016/j.ijgo.2015.07.024.
Del Pino M, Alonso I, Rodriguez-Trujillo A, Bernal S, Geraets D, Guimerà N, et al. Comparison of the analytical and clinical performance of five tests for the detection of Human Papillomavirus genital infection. J Virol Methods. 2017;248:238-43. doi: 10.1016/j.jviromet.2017.07.009.
Alba I, Anton-Culver H, Hubbell FA, Ziogas A, Hess JR, Bracho A, et al. Self-sampling for Human Papillomavirus in a community setting: feasibility in Hispanic women. Cancer Epidemiol Biomark Prev. 2008;17(8):2163-8. doi: 10.1158/1055-9965.


