Does CIN2 Have the Same Aggressive Potential As CIN3? A Secondary Analysis of High-Grade Cytology Recurrence in Women Treated with Cold-Coagulation Cervical Treatment

Abstract

Introduction To determine whether women with CIN2 versus CIN3 on pretreatment cervical punch biopsy have less high-grade cytology recurrence following cold-coagulation cervical treatment.

Materials and Methods This was a retrospective study of women having had cold coagulation between 2001–2011 in our colposcopy unit. Women with previous cervical treatment were excluded.

Results We identified 402 women with 260 (64.7 %) cases of CIN2 and 142 (35.3 %) cases of CIN3 on pretreatment cervical punch biopsy. In the total sample, the mean age of women was 27.5 years (SD = 4.9), 75.1 % were nulliparous and 36.6 % were smokers. Referral cytology and pretreatment colposcopic appearance were high-grade in 62.7 % and 57.1 %. The mean follow-up period was 2.8 years (SD = 2.1). Women with CIN2 on pretreatment cervical biopsy when compared to those with CIN3 had less frequently high-grade referral cytology and high-grade pretreatment colposcopic appearances, and had less pretreatment cervical biopsies taken. During the follow-up period, women with CIN2 on pretreatment cervical biopsy had less high-grade cytology recurrence when compared to those women with CIN3 (1.9 vs. 5.6 %, p = 0.046). Multiple stepwise Cox regression analysis showed that women with CIN3 on pretreatment cervical biopsy had 3.21 times greater hazard for high-grade cytology recurrence (HR = 3.21, 95 % CI: 1.05–9.89; p = 0.041) in comparison with CIN2 cases.

Conclusion We found that women with CIN2 on pretreatment cervical punch biopsy had less high-grade cytology recurrence following cold-coagulation treatment in comparison to those with CIN3. This finding lends support to the theory that CIN2 even though a high-grade abnormality might not have the same aggressive potential as CIN3.

Zusammenfassung

Einleitung Ziel der Studie war es, die Häufigkeit von hochgradigen Rezidiven bei Frauen mit CIN-II-Läsionen zu ermitteln, verglichen mit Frauen mit CIN III. Der CIN-II- bzw. CIN-III-Befund basierte auf Stanzbiopsien. Nach der Befundung bestand die Behandlung bei allen Frauen aus einer Kaltkoagulation.

Material und Methoden Es handelt sich um eine retrospektive Untersuchung von Frauen, die zwischen 2001 und 2011 in unserer Kolposkopie-Abteilung behandelt wurden. Frauen, die sich bereits zuvor einer anderen Zervixbehandlung unterzogen hatten, wurden von der Studie ausgeschlossen.

Ergebnisse Insgesamt wurden 402 Frauen untersucht; davon hatten laut Stanzbiopsie 260 Frauen (64,7 %) CIN-II- und 142 Frauen (35,3 %) CIN-III-Läsionen. Das Durchschnittsalter aller in der Studie eingeschlossenen Frauen war 27,5 Jahre (SD = 4,9); davon waren 75,1 % Nullipara und 36,6 % waren Raucherinnen. Basierend auf dem zytologischem Befund und dem kolposkopischen Erscheinungsbild vor der Behandlung hatten 62,7 bzw. 57,1 % der untersuchten Frauen hochgradige Läsionen. Die mittlere Nachbeobachtungszeit betrug 2,8 Jahre (SD = 2,1). Frauen, bei denen vor der Behandlung eine CIN II durch Stanzbiopsie ermittelt wurde, hatten seltener einen hochgradigen zytologischen Befund bzw. ein hochgradiges Erscheinungsbild verglichen mit Frauen mit CIN III, und die Anzahl der vor der Behandlung entnommenen Zervixbiopsien war geringer. Im Nachbeobachtungszeitraum gab es weniger hochgradige Rezidive bei Frauen mit CIN II verglichen mit Frauen, bei denen zuvor eine CIN III zytologisch nachgewiesen wurde (1,9 vs. 5,6 %, p = 0,046). Nach der schrittweisen multiplen Regression nach Cox war das Risiko bei Frauen, bei denen vor der Behandlung eine CIN III mit Stanzbiopsie nachgewiesen wurde, nach der Behandlung ein hochgradiges Rezidiv zu entwickeln, 3,21-mal höher (HR = 3,21, 95 %-KI: 1,05–9,89; p = 0,041) als bei Frauen mit CIN II.

Schlussfolgerung Unsere Ergebnisse zeigen, dass Frauen, bei denen vor der Behandlung eine CIN II durch Stanzbiopsie ermittelt wurde, weniger zytologisch nachweisbare hochgradige Rezidive nach der Behandlung mit Kaltkoagulation entwickelten als Frauen mit CIN III. Dieses Ergebnis stützt die Hypothese, dass, auch wenn die CIN II als hochgradige Anomalie eingestuft wird, CIN II nicht dasselbe aggressive Potenzial wie CIN III hat.

Key words

cold coagulation - cytology recurrence - CIN

Schlüsselwörter

Kaltkoagulation - zytologisch nachgewiesenes Rezidiv - CIN

• References

• 1 Katki HA, Schiffman M, Castle PE. et al. Five-year risks of CIN 3+ and cervical cancer among women with HPV-positive and HPV-negative high-grade Pap results. J Low Genit Tract Dis 2013; 17: S50-S55
• 2 Darragh TM, Colgan TJ, Cox JT. et al. Members of LAST Project Work Groups. 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: 205-242
• 3 Insinga RP, Dasbach EJ, Elbasha EH. Epidemiologic natural history and clinical management of Human Papillomavirus (HPV) Disease: a critical and systematic review of the literature in the development of an HPV dynamic transmission model. BMC Infect Dis 2009; 9: 119
• 4 Peto J, Gilham C, Fletcher O. et al. The cervical cancer epidemic that screening has prevented in the UK. Lancet 2004; 364: 249-256
• 5 Gustafsson L, Adami HO. Natural history of cervical neoplasia: consistent results obtained by an identification technique. Br J Cancer 1989; 60: 132-141
• 6 McCredie MR, 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: 425-434
• 7 Moore K, Cofer A, Elliot L. et al. Adolescent cervical dysplasia: histologic evaluation, treatment, and outcomes. Am J Obstet Gynecol 2007; 197: 141.e1-141.e6
• 8 McAllum B, Sykes PH, Sadler L. et al. Is the treatment of CIN 2 always necessary in women under 25 years old?. Am J Obstet Gynecol 2011; 205: 478.e1-478.e7
• 9 Munro A, Powell RG, ACohen AP. et al. Spontaneous regression of CIN2 in women aged 18–24 years: a retrospective study of a state-wide population in Western Australia. Acta Obstet Gynecol Scand 2016; 95: 291-298
• 10 Moscicki AB, Ma Y, Wibbelsman C. et al. Rate of and risks for regression of cervical intraepithelial neoplasia 2 in adolescents and young women. Obstet Gynecol 2010; 116: 1373-1380
• 11 Discacciati MG, de Souza CA, dʼOtavianno MG. et al. Outcome of expectant management of cervical intraepithelial neoplasia grade 2 in women followed for 12 months. Eur J Obstet Gynecol Reprod Biol 2011; 155: 204-208
• 12 Castle PE, Schiffman M, Wheeler CM. et al. Evidence for frequent regression of cervical intraepithelial neoplasia-grade 2. Obstet Gynecol 2009; 113: 18-25
• 13 Parry-Smith W, Underwood M, De Bellis-Ayres S. et al. Success rate of cold coagulation for the treatment of cervical intraepithelial neoplasia: a retrospective analysis of a series of cases. J Low Genit Tract Dis 2015; 19: 17-21
• 14 Milenković V, Sparić R, Dotlić J. et al. Reliability and relationship of colposcopical, cytological and histopathological findings in the diagnostic process. Vojnosanit Pregl 2012; 69: 869-873
• 15 NHSCSP. Colposcopy and Programme Management. Guidelines for the NHS cervical Screening Programme. 3rd ed. Sheffield, England: NHSCSP Publication No. 20; March 2016.
• 16 Castle PE, Stoler MH, Solomon D. et al. The relationship of community biopsy-diagnosed cervical intraepithelial neoplasia grade 2 to the quality control pathology-reviewed diagnoses: an ALTS report. Am J Clin Pathol 2007; 127: 805-815
• 17 Stoler MH, Schiffman M. Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage Study. JAMA 2001; 285: 1500-1505
• 18 Dalla Palma P, Giorgi Rossi P, Collina G. et al. The reproducibility of CIN diagnoses among different pathologists: data from histology reviews from a multicenter randomized study. Am J Clin Pathol 2009; 132: 125-132
• 19 Carreon JD, Sherman ME, Guillén D. et al. CIN2 is a much less reproducible and less valid diagnosis than CIN3: results from a histological review of population-based cervical samples. Int J Gynecol Pathol 2007; 26: 441-446
• 20 Massad LS, Einstein MH, Huh WK. et al. 2012 ASCCP Consensus Guidelines Conference. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol 2013; 121: 829-846
• 21 Sasieni P, Castanon A, Cuzick J. Effectiveness of cervical screening with age: population based case-control study of prospectively recorded data. BMJ 2009; 339: b2968
• 22 Ostör AG. Natural history of cervical intraepithelial neoplasia: a critical review. Int J Gynecol Pathol 1993; 12: 186-192
• 23 Chenoy R, Billingham L, Irani S. et al. The effect of directed biopsy on the atypical cervical transformation zone: assessed by digital imaging colposcopy. Br J Obstet Gynaecol 1996; 103: 457-462
• 24 Kyrgiou M, Mitra A, Arbyn M. et al. Fertility and early pregnancy outcomes after conservative treatment for cervical intraepithelial neoplasia. Cochrane Database Syst Rev 2015; (09) CD008478
• 25 Uleberg KE, Munk AC, Brede C. et al. Discrimination of grade 2 and 3 cervical intraepithelial neoplasia by means of analysis of water soluble proteins recovered from cervical biopsies. Proteome Sci 2011; 9: 36
• 26 Baak JPA, Kruse AJ, Robboy SJ. et al. Dynamic behavioural interpretation of cervical intraepithelial neoplasia with molecular biomarkers. J Clin Pathol 2006; 59: 1017-1028
• 27 Abulafia O, Pezzullo JC, Sherer DM. Performance of ThinPrep liquid-based cervical cytology in comparison with conventionally prepared Papanicolaou smears: a quantitative survey. Gynecol Oncol 2003; 90: 137-144