Individualizovaná chirurgická léčba cervikálních prekanceróz

English version

Autoři: B. Sehnal ¹; D. Driák ¹ ; D. Cibula ²; M. Halaška ¹; P. Bolehovská ¹; J. Sláma ²
Působiště autorů: Onkogynekologické centrum, Gynekologicko-porodnická klinika 1. LF UK a Nemocnice Na Bulovce, Praha, přednosta prof. MUDr. M. Halaška, DrSc. ¹; Onkogynekologické centrum, Gynekologicko-porodnická klinika 1. LF UK a VFN, Praha, přednosta prof. MUDr. A. Martan, DrSc. ²
Vyšlo v časopise: Ceska Gynekol 2014; 79(5): 372-377

Souhrn

Cíl studie:
Přehled nových znalostí, které by mohly pomoci v rozhodování o individualizované léčbě prekanceróz děložního hrdla.

Typ studie:
Souhrnný přehled.

Název a sídlo pracoviště:
Onkogynekologické centrum, Gynekologicko-porodnická klinika, Nemocnice Na Bulovce a 1. LF UK, Praha; Onkogynekologické centrum, Gynekologicko-porodnická klinika Všeobecné fakultní nemocnice a 1. LF UK, Praha.

Metodika a výsledky:
Prekancerózy děložního hrdla jsou zastoupeny dlaždicobuněčnými cervikálními intraepiteliálními neoplaziemi (CIN) a žlázovými adenocarcinomy in situ (AIS). Obvyklou léčbou prekanceróz děložního hrdla je konizace. Avšak některé komplikace, zvláště nežádoucí následky v pozdější graviditě, mohou doprovázet jakoukoliv chirurgickou léčbu děložního hrdla. U žen, které si přejí otěhotnět a mají CIN s nízkým rizikem transformace do invazivního karcinomu, může být terapie odložena. Výskyt blíže specifikujících faktorů by mohl pomoci rozčlenit CIN podle jejich maligního potenciálu. Význam by mohlo mít stanovení HPV genotypu, protože osud CIN 2/3 závisí na genotypu asociované HPV infekce. Cervikální léze spojené s HPV 16, 18 a 45 mají výrazně vyšší riziko progrese do invazivního karcinomu než léze asociované s jinými HR HPV genotypy. V individuálních případech by chirurgická léčba CIN 2/3 mohla být odložena u žen, které si přejí otěhotnět, pokud by léze nebyla asociována s HPV 16, 18 a 45. Použití biologických a molekulárních markerů, především p16INK4a, se pokouší upřesnit zhodnocení cervikálních lézí. Mladší věk, probíhající těhotenství, příznivý kolposkopický nález, negativní p16^INK4aa neoslabená imunita jsou nezávislé faktory podporující konzervativní management. Léčba adenocarcinomu in situ se podstatně liší od managementu CIN.

Závěr:
Je důležité správně zhodnotit všechny upřesňující okolnosti a minimalizovat nežádoucí účinky v důsledku zbytečné či nadbytečné chirurgické léčby prekanceróz děložního hrdla.

Klíčová slova:
cervikální intraepiteliální neoplazie, adenocarcinoma in situ, konizace, individualizovaná léčba, genotyp lidského papilomaviru, p16

Zdroje

1. Albrechtsen, S., Rasmussen, S., Thoresen, S., et al. Preg-nancy outcome in women before and after cervical conisation: population based cohort study. BMJ, 2008, 337, a1343.

2. Arbyn, M., Kyrgiou, M., Simoens, C., et al. Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: meta-analysis. BMJ, 2008, 337(7673), p. 798–808.

3. Bosch, FX., Lorincz, A., Munoz, N., et al. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol, 2002, 55, p. 244–265.

4. Bray, F., Carstensen, B., Moller, H., et al. Incidence trends of adenocarcinoma of the cervix in 13 European countries. Cancer Epidemiol Biomarkers Prev, 2005, 14, p. 2191–2199.

5. Bull-Phelps, SL., Garner, EI., Walsh, CS., et al. Fertility-sparing surgery in 101 women with adenocarcinoma in situ of the cervix. Gynecol Oncol, 2007, 107, p. 316–319.

6. Castle, PE., Dockter, J., Giachetti, C., et al. A cross-sectional study of a prototype carcinogenic human papillomavirus E6/E7 messenger RNA assay for detection of cervical precancer and cancer. Clin Cancer Res, 2007, 13, p. 2599–2605.

7. Connor, JP. Noninvasive cervical cancer complicating pregnancy. Obstet Gynecol Clin North Am, 1998, 25, p. 331–342.

8. Costa, S., Venturoli, S., Negri, G., et al. Factors predicting the outcome of conservatively treated adenocarcinoma in situ of the uterine cervix: an analysis of 166 cases. Gynecol Oncol, 2012, 124, p 490–495.

9. de Sanjose, S., Quint, WGV., Alemany, L., et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective crosssectional worldwide study. Lancet Oncol, 2010, 11, p. 1048–1056.

10. Fuchs, K., Weitzen, S., Wu, L., et al. Management of cervical intraepithelial neoplasia 2 in adolescent and young women.J Pediatr Adolesc Gynecol, 2007, 20, p. 269–274.

11. Guo, M., Warriage, I., Mutyala, B., et al. Evaluation of p16 immunostaining to predict high-grade cervical intraepithelial neo-plasia in women with Pap results of atypical squamous cells of undetermined significance. Diagn Cytopathol, 2011, 39(7), p. 482–488.

12. Horn, LC., Reichert, A., Oster, A., et al. Immunostaining for p16INK4a used as a conjunctive tool improves interobserver agreement of the histologic diagnosis of cervical intraepithelial neoplasia. Am J Surg Pathol, 2008, 32(4), p. 502–512.

13. Iaconis, L., Hyjek, E., Ellenson, LH., Pirog, EC. p16 and Ki-67 immunostaining in atypical immature squamous metaplasia of the uterine cervix: correlation with human papillomavirus detection. Arch Pathol Lab Med, 2007, 131(9), p. 1343–1349.

14. IARC. Globocan 2008, Section of Cancer Information. Available at: http://globocan.iarc.fr/ factsheets/cancers/cervix.asp. X1.

15. Jolley, JA., Wing, DA. Pregnancy management after cervical surgery. Curr Opin Obstet Gynecol, 2008, 20(6), p. 528–533.

16. Jordan, J., Arbyn, M., Martin-Hirsch, P., et al. European guidelines for clinical management of abnormal cervical cytology, part 2. Cytopathology, 2009, 20(1), p. 5–16.

17. Katki, HA., Gage, JC., Schiffman, M., et al. Follow-up testing after colposcopy: five-year risk of CIN 2+ after a colposcopic diagnosis of CIN 1 or less. J Low Genit Tract Dis, 2013, 5, p. S69–S77.

18. Kim, TJ., Kim, HS., Park, CT., et al. Clinical evaluation of follow-up methods and results of atypical glandular cells of undetermined significance (AGUS) detected on cervicovaginal Pap smears. Gynecol Oncol, 1999, 73(2), p. 292–298.

19. Kyrgiou, M., Koliopoulos, G., Martin-Hirsch, P., et al. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet, 2006, 367(9509), p. 489–498.

20. Kyrgiou, M., Tsoumpou, I., Vrekoussis, T., et al. The up-to-date evidence on colposcopy practice and treatment of cervical intraepithelial neoplasia: the Cochrane colposcopy and cervical cytopathology collaborative group (C5 group) approach. Cancer Treat Rev, 2006, 32, p. 516–523.

21. Lee, H., Lee, KJ., Jung, CK., et al. Expression of HPV L1 capsid protein in cervical specimens with HPV infection. Diagn Cytopathol, 2008, 36, p. 864–867.

22. Liverani, CA., Ciavattini, A., Monti, E., et al. High risk HPV DNA subtypes and E6/E7 mRNA expression in a cohort of colposcopy patients from Northern Italy with high-grade histologically verified cervical lesions. Am J Transl Res, 2012, 4(4), p. 452–547.

23. Looi, ML., Karsani, SA., Rahman, MA., et al. Plasma proteome analysis of cervical intraepithelial neoplasia and cervical squamous cell carcinoma. J Biosci, 2009, 34(6), p. 917–925.

24. Martin-Hirsch, PPL., Paraskevaidis, E., Bryant, A., et al. Surgery for cervical intraepithelial neoplasia. Cochrane Database of Systematic Reviews, 2013. Available at: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001318.pub3

25. Massad, LS., Einstein, MH., Warner, KH., et al. American Society for Colposcopy and Cervical Pathology. 2012 Updated Consensus Guidelines for the Management of Abnormal Cervical Cancer Screening Tests and Cancer Precursors. J Low Genit Tract Dis, 2013, 17(5), p. S1–S27.

26. Matthews, KS., Rocconi, RP., Case, AS., et al. Diagnostic loop electrosurgical excisional procedure for discrepancy: do preoperative factors predict presence of significant cervical intraepithelial neoplasia? J Low Genit Tract Dis, 2007, 11(2), p. 69–72.

27. McCredie, MRE., Sharples, KJ., Paul, C., et al. Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncol, 2008, 9, p. 425–434.

28. Melsheimer, P., Kaul, S., Dobeck, S., Bastert, G. Immu-nocytochemical 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, p. 124–128.

29. Mitchell, MF., Tortolero-Luna, G., Wright, T., et al. Cervical human papillomavirus infection and intraepithelial neoplasia: a review. J Natl Cancer Inst Monogr, 1996, 21, p. 17–25.

30. Molden, T., Kraus, I., Karlsen, F., et al. Human papillomavirus E6/E7 mRNA expression in women younger than 30 years of age. Gynecol Oncol, 2006, 100, p. 95–100.

31. Moscicki, AB., Ma, Y., Wibblesman, C., et al. Rate of and risks for regression of cervical intraepithelial neoplasia 2 in adolescents and young women. Obstet Gynecol, 2010, 116, p. 1373–1380.

32. Murphy, N., Ring, M., Heffron, CC., et al. p16INK4A, CDC6, and MCM5: predictive biomarkers in cervical preinvasive neoplasia and cervical cancer. J Clin Pathol, 2005, 5(5), p. 525–534.

33. Negri, G., Vittadello, F., Romano, F., et al. p16INK4a expression and progression risk of low-grade intraepithelial neoplasia of the cervix uteri. Virchows Arch, 2004, 445(6), p. 616–620.

34. Nuovo, J., Melnikow, J., Willan, AR., Chan, BK. Treatment outcomes for squamous intraepithelial lesions. Int J Gynaecol Obstet, 2000, 68, p. 25–33.

35. Ostor, AG. Natural history of cervical intraepithelial neoplasia: A critical review. Intern J Gynecol Pathol, 1993, 12, p. 186–192.

36. Prendiville, W. The treatment of CIN: what are the risks? Cytopathology, 2009, 20, p. 145–153.

37. Safaeian, M., Schiffman, M., Gage, J., et al. Detection of precancerous lesions is differential by human papillomavirus type. Cancer Res, 2009, 69, p. 3262–3266.

38. Seoud, M., Tjalma, WA., Ronsse, V. Cervical adenocarcinoma: moving towards better prevention. Vaccine, 2011, 29, p. 9148–9158.

39. Sherman, ME., Wang, SS., Carreon, J., et al. Mortality trends for cervical squamous and adenocarcinoma in the United States. Relation to incidence and survival. Cancer, 2005, 103, p. 1258–1264.

40. Schiffman, M., Castle, PE., Jeronimo, J., et al. Human papillomavirus and cervical cancer. Lancet, 2007, 370, p. 890–907.

41. Schiffman, M., Wentzensen, N., Wacholder, S., et al. Human papillomavirus testing in the prevention of cervical cancer. J Natl Cancer Inst, 2011, 103, p. 368–383.

42. Sideri, M., Iqidbashian, S., Boveri, S., et al. Age distribution of HPV genotypes in cervical intraepithelial neoplasia. Gynecol Oncol, 2011, 212, p. 510–513.

43. Slama, J., Adamcova, K., Dusek, L., et al. Umbilication is a strong predictor of high-grade cervical intraepithelial neoplasia. J Low Genit Tract Dis, 2013, 17(3), p. 303–307.

44. Slama, J. The new colposcopic signs-ridge sign and inner border. Ces Gynek, 2012, 77(1), p. 22–24.

45. Spitzer, M., Apgar, BS., Brotzman, GL. Management of histologic abnormalities of the cervix. Am Fam Physician, 2006, 73, p. 105–112.

46. Spitzer, M., Chernys, AE., Shifrin, A., Ryskin, M. Indications for cone biopsy: pathologic correlation. Am J Obstet Gynecol, 1998, 178, p. 74–79.

47. Srivastava, S. p16INK4A and MIB-1: An immunohistochemical expression in preneoplasia and neoplasia of the cervix. Indian J Pathol Microbiol, 2010, 53, p. 518–524.

48. Systém pro vizualizaci onkologických dat. Institut biostatistiky a analýz Lékařské a Přírodovědecké fakulty Masarykovy univerzity (IBA MU). Available at: www.svod.cz

49. Tjalma, WA., Fiander, A., Reich, O., et al. Differences in human papillomavirus type distribution in high-grade cervical intraepithelial neoplasia and invasive cervical cancer in Europe Int J Cancer, 2013, 132, p. 854–867.

50. Uleberg, KE., Munk, AC., Skaland, I., et al. A protein profile study to discriminate CIN lesions from normal cervical epithelium. Cell Oncol, 2011, 34, p. 443–450.

51. van Hanegem, N., Barroilhet, LM., Nucci, MR., et al. Fertility-sparing treatment in younger women with adenocarcinoma in situ of the cervix. Gynecol Oncol, 2012, 124, p. 2–77.

52. Walboomers, JMM., Jacobs, MV., Manos, MM., et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol, 1999, 189, p. 12–19.

53. Walts, AE., Bose, S. p16, Ki-67, and BD ProEx™C immunostaining: a practical approach for diagnosis of cervical intraepithelial neoplasia. Hum Pathol, 2009, 40(7), p. 957–964.

54. Watson, LF., Rayner, JA., King, J., et al. Intracervical procedures and the risk of subsequent very preterm birth: a case-control study. Acta Obstet Gynecol Scand, 2012, 91(2), p. 204–210.

55. Waxman, AG., Chelmow, D., Darragh, TM., et al. Revised terminology for cervical histopathology and its implications for managment of high-grade squamous intraepithelial lesions of the cervix. Obstet Gyn Oncol, 2012, 120(6), p. 1465–1471.

56. Yemelyanova, A., Gravitt, PE., Ronnett, BM., et al. Immu-nohistochemical detection of Human Papillomavirus capsid proteins L1 and L2 in squamous intraepithelial lesions: Potential utility in diagnosis and management. Mod Pathol, 2013, 26(2), p. 268–274.

57.Yost, NP., Santoso, JT., McIntire, DD., Iliya, FA. Postpartum regression rates of antepartum cervical intraepithelial neoplasia II and III lesions. Obstet Gynecol, 1999, 93, p. 359–362.