J Gynecol Oncol.  2012 Oct;23(4):217-225. 10.3802/jgo.2012.23.4.217.

Early human papillomavirus testing predicts residual/recurrent disease after LEEP

Affiliations
  • 1Department of Obstetrics & Gynecology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea. khnam@schmc.ac.kr
  • 2Department of Pathology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.

Abstract


OBJECTIVE
The purpose of this study was to determine the predictive factors for residual/recurrent disease and to analyze the timing for Pap smears and human papillomavirus (HPV) testing during follow-up after loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN) 2 or worse.
METHODS
We retrospectively analyzed 183 patients (mean age, 39.3 years) with CIN 2/3 who were treated with LEEP. Post-LEEP follow-up was performed by Pap smear and HPV hybrid capture2 (HC2) testing. The definition of persistent/recurrent disease was biopsy-proven CIN 2 or worse.
RESULTS
Among 183 patients, punch biopsies were CIN 2 in 31 (16.9%) and CIN 3 in 152 (83.1%). HPV HC2 tests before LEEP were positive in 170 (95.5%) of 178 patients. During follow-up, 12 patients (6.6%) had residual/recurrent CIN 2+. LEEP margin status was a significant predictive factor for persistent/recurrent disease. Other factors such as age, HPV HC2 viral load (> or =100 relative light units), and HPV typing (type 16/18 vs. other types) did not predict recurrence. Early HPV HC2 testing at 3 months after LEEP detected all cases of residual/recurrent disease. The sensitivity and negative predictive value of the HPV HC2 test for residual/recurrent disease were both 100% at 3 and 6 months.
CONCLUSION
Margin involvement in conization specimens was a significant factor predicting residual/recurrent disease after LEEP. HPV test results at 3 and 6 months after treatment were comparable. Early 3-month follow-up testing after LEEP can offer timely information about residual/recurrent disease and alleviate patient anxiety early about treatment failure.

Keyword

Cervical intraepithelial neoplasia; Follow-up; Human papillomavirus; Loop electrosurgical excision procedure

MeSH Terms

Anxiety
Biopsy
Cervical Intraepithelial Neoplasia
Chimera
Conization
Follow-Up Studies
Humans
Light
Recurrence
Retrospective Studies
Treatment Failure
Viral Load

Cited by  2 articles

Posttreatment human papillomavirus testing for residual or recurrent high-grade cervical intraepithelial neoplasia: a pooled analysis
Mamiko Onuki, Koji Matsumoto, Manabu Sakurai, Hiroyuki Ochi, Takeo Minaguchi, Toyomi Satoh, Hiroyuki Yoshikawa
J Gynecol Oncol. 2016;27(1):e3.    doi: 10.3802/jgo.2016.27.e3.

Posttreatment human papillomavirus testing for residual or recurrent high-grade cervical intraepithelial neoplasia: a pooled analysis
Mamiko Onuki, Koji Matsumoto, Manabu Sakurai, Hiroyuki Ochi, Takeo Minaguchi, Toyomi Satoh, Hiroyuki Yoshikawa
J Gynecol Oncol. 2016;27(1):.    doi: 10.3802/jgo.2016.27.e3.


Reference

1. McCredie MR, Sharples KJ, Paul C, Baranyai J, Medley G, Jones RW, 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.
2. Pinto AP, Crum CP. Natural history of cervical neoplasia: defining progression and its consequence. Clin Obstet Gynecol. 2000. 43:352–362.
3. Prendiville W, Cullimore J, Norman S. Large loop excision of the transformation zone (LLETZ): a new method of management for women with cervical intraepithelial neoplasia. Br J Obstet Gynaecol. 1989. 96:1054–1060.
4. Lindeque BG. Management of cervical premalignant lesions. Best Pract Res Clin Obstet Gynaecol. 2005. 19:545–561.
5. Mitchell MF, Tortolero-Luna G, Cook E, Whittaker L, Rhodes-Morris H, Silva E. A randomized clinical trial of cryotherapy, laser vaporization, and loop electrosurgical excision for treatment of squamous intraepithelial lesions of the cervix. Obstet Gynecol. 1998. 92:737–744.
6. Ghaem-Maghami S, Sagi S, Majeed G, Soutter WP. Incomplete excision of cervical intraepithelial neoplasia and risk of treatment failure: a meta-analysis. Lancet Oncol. 2007. 8:985–993.
7. Soutter WP, Sasieni P, Panoskaltsis T. Long-term risk of invasive cervical cancer after treatment of squamous cervical intraepithelial neoplasia. Int J Cancer. 2006. 118:2048–2055.
8. Soutter WP. Invasive cancer after treatment of cervical intraepithelial neoplasia. Ann Acad Med Singapore. 1998. 27:722–724.
9. Soutter WP, de Barros Lopes A, Fletcher A, Monaghan JM, Duncan ID, Paraskevaidis E, et al. Invasive cervical cancer after conservative therapy for cervical intraepithelial neoplasia. Lancet. 1997. 349:978–980.
10. Strander B, Andersson-Ellstrom A, Milsom I, Sparen P. Long term risk of invasive cancer after treatment for cervical intraepithelial neoplasia grade 3: population based cohort study. BMJ. 2007. 335:1077.
11. Costa S, De Simone P, Venturoli S, Cricca M, Zerbini ML, Musiani M, et al. Factors predicting human papillomavirus clearance in cervical intraepithelial neoplasia lesions treated by conization. Gynecol Oncol. 2003. 90:358–365.
12. Alonso I, Torne A, Puig-Tintore LM, Esteve R, Quinto L, Campo E, et al. Pre- and post-conization high-risk HPV testing predicts residual/recurrent disease in patients treated for CIN 2-3. Gynecol Oncol. 2006. 103:631–636.
13. Nagai Y, Maehama T, Asato T, Kanazawa K. Persistence of human papillomavirus infection after therapeutic conization for CIN 3: is it an alarm for disease recurrence? Gynecol Oncol. 2000. 79:294–299.
14. Nam K, Chung S, Kim J, Jeon S, Bae D. Factors associated with HPV persistence after conization in patients with negative margins. J Gynecol Oncol. 2009. 20:91–95.
15. Wright TC Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D, et al. 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ. Am J Obstet Gynecol. 2007. 197:340–345.
16. Heley S. Pap test update. Aust Fam Physician. 2007. 36:112–115.
17. Nam K, Chung S, Kwak J, Cha S, Kim J, Jeon S, et al. Random biopsy after colposcopy-directed biopsy improves the diagnosis of cervical intraepithelial neoplasia grade 2 or worse. J Low Genit Tract Dis. 2010. 14:346–351.
18. Clavel C, Cucherousset J, Lorenzato M, Caudroy S, Nou JM, Nazeyrollas P, et al. Negative human papillomavirus testing in normal smears selects a population at low risk for developing high-grade cervical lesions. Br J Cancer. 2004. 90:1803–1808.
19. Sarian LO, Derchain SF, Andrade LA, Tambascia J, Morais SS, Syrjanen KJ. HPV DNA test and Pap smear in detection of residual and recurrent disease following loop electrosurgical excision procedure of high-grade cervical intraepithelial neoplasia. Gynecol Oncol. 2004. 94:181–186.
20. Kang WD, Oh MJ, Kim SM, Nam JH, Park CS, Choi HS. Significance of human papillomavirus genotyping with high-grade cervical intraepithelial neoplasia treated by a loop electrosurgical excision procedure. Am J Obstet Gynecol. 2010. 203:72.e1–72.e6.
21. Verguts J, Bronselaer B, Donders G, Arbyn M, Van Eldere J, Drijkoningen M, et al. Prediction of recurrence after treatment for high-grade cervical intraepithelial neoplasia: the role of human papillomavirus testing and age at conisation. BJOG. 2006. 113:1303–1307.
22. Kreimer AR, Guido RS, Solomon D, Schiffman M, Wacholder S, Jeronimo J, et al. Human papillomavirus testing following loop electrosurgical excision procedure identifies women at risk for posttreatment cervical intraepithelial neoplasia grade 2 or 3 disease. Cancer Epidemiol Biomarkers Prev. 2006. 15:908–914.
23. Wright TC Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D, et al. 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ. J Low Genit Tract Dis. 2007. 11:223–239.
24. Sarian LO, Derchain SF, Pitta Dda R, Morais SS, Rabelo-Santos SH. Factors associated with HPV persistence after treatment for high-grade cervical intra-epithelial neoplasia with large loop excision of the transformation zone (LLETZ). J Clin Virol. 2004. 31:270–274.
25. Houfflin Debarge V, Collinet P, Vinatier D, Ego A, Dewilde A, Boman F, et al. Value of human papillomavirus testing after conization by loop electrosurgical excision for high-grade squamous intraepithelial lesions. Gynecol Oncol. 2003. 90:587–592.
26. Jain S, Tseng CJ, Horng SG, Soong YK, Pao CC. Negative predictive value of human papillomavirus test following conization of the cervix uteri. Gynecol Oncol. 2001. 82:177–180.
27. Lin CT, Tseng CJ, Lai CH, Hsueh S, Huang KG, Huang HJ, et al. Value of human papillomavirus deoxyribonucleic acid testing after conization in the prediction of residual disease in the subsequent hysterectomy specimen. Am J Obstet Gynecol. 2001. 184:940–945.
28. Cricca M, Venturoli S, Morselli-Labate AM, Costa S, Santini D, Ambretti S, et al. HPV DNA patterns and disease implications in the follow-up of patients treated for HPV16 high-grade carcinoma in situ. J Med Virol. 2006. 78:494–500.
29. Zielinski GD, Rozendaal L, Voorhorst FJ, Berkhof J, Snijders PJ, Risse EJ, et al. HPV testing can reduce the number of follow-up visits in women treated for cervical intraepithelial neoplasia grade 3. Gynecol Oncol. 2003. 91:67–73.
30. Chua KL, Hjerpe A. Human papillomavirus analysis as a prognostic marker following conization of the cervix uteri. Gynecol Oncol. 1997. 66:108–113.
31. McCaffery K, Waller J, Forrest S, Cadman L, Szarewski A, Wardle J. Testing positive for human papillomavirus in routine cervical screening: examination of psychosocial impact. BJOG. 2004. 111:1437–1443.
32. Kola S, Walsh JC. Patients' psychological reactions to colposcopy and LLETZ treatment for cervical intraepithelial neoplasia. Eur J Obstet Gynecol Reprod Biol. 2009. 146:96–99.
33. Coupe VM, Berkhof J, Verheijen RH, Meijer CJ. Cost-effectiveness of human papillomavirus testing after treatment for cervical intraepithelial neoplasia. BJOG. 2007. 114:416–424.
34. Dalstein V, Riethmuller D, Pretet JL, Le Bail Carval K, Sautiere JL, Carbillet JP, et al. Persistence and load of high-risk HPV are predictors for development of high-grade cervical lesions: a longitudinal French cohort study. Int J Cancer. 2003. 106:396–403.
35. Franco EL, Villa LL, Sobrinho JP, Prado JM, Rousseau MC, Desy M, et al. Epidemiology of acquisition and clearance of cervical human papillomavirus infection in women from a high-risk area for cervical cancer. J Infect Dis. 1999. 180:1415–1423.
36. Park JY, Lee KH, Dong SM, Kang S, Park SY, Seo SS. The association of pre-conization high-risk HPV load and the persistence of HPV infection and persistence/recurrence of cervical intraepithelial neoplasia after conization. Gynecol Oncol. 2008. 108:549–554.
37. Bae JH, Kim CJ, Park TC, Namkoong SE, Park JS. Persistence of human papillomavirus as a predictor for treatment failure after loop electrosurgical excision procedure. Int J Gynecol Cancer. 2007. 17:1271–1277.
38. Gok M, Coupe VM, Berkhof J, Verheijen RH, Helmerhorst TJ, Hogewoning CJ, et al. HPV16 and increased risk of recurrence after treatment for CIN. Gynecol Oncol. 2007. 104:273–275.
39. Wu D, Zheng Y, Chen W, Guo C, Yu J, Chen G, et al. Prediction of residual/recurrent disease by HPV genotype after loop excision procedure for high-grade cervical intraepithelial neoplasia with negative margins. Aust N Z J Obstet Gynaecol. 2011. 51:114–118.
40. Paraskevaidis E, Kalantaridou SN, Paschopoulos M, Zikopoulos K, Diakomanolis E, Dalkalitsis N, et al. Factors affecting outcome after incomplete excision of cervical intraepithelial neoplasia. Eur J Gynaecol Oncol. 2003. 24:541–543.
41. Paraskevaidis E, Lolis ED, Koliopoulos G, Alamanos Y, Fotiou S, Kitchener HC. Cervical intraepithelial neoplasia outcomes after large loop excision with clear margins. Obstet Gynecol. 2000. 95:828–831.
Full Text Links
  • JGO
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr