DOI QR코드

DOI QR Code

Pap Smear Combined with HPV Testing: A Reasonable Tool for Women with High-grade Cervical Intraepithelial Neoplasia Treated by LEEP

  • Mo, Ling-Zhao (Department of Gynecological Oncology, Tumor Hospital Affiliated to Guangxi Medical University) ;
  • Song, Hong-Lin (Department of Gynecological Oncology, Tumor Hospital Affiliated to Guangxi Medical University) ;
  • Wang, Jian-Li (Department of Gynecological Oncology, Tumor Hospital Affiliated to Guangxi Medical University) ;
  • He, Qing (Department of Gynecological Oncology, Tumor Hospital Affiliated to Guangxi Medical University) ;
  • Qiu, Zhang-Can (Department of Gynecological Oncology, Tumor Hospital Affiliated to Guangxi Medical University) ;
  • Li, Fei (Department of Gynecological Oncology, Tumor Hospital Affiliated to Guangxi Medical University)
  • Published : 2015.06.03

Abstract

Background: To evaluate HPV testing by Hybrid Capture II (HCII) in conjunction with cytology in detecting the residual/recurrence disease after treatment of high-grade cervical intraepithelial neoplasia (CIN II-III) with loop electrosurgical excision procedure (LEEP). Materials and Methods: A retrospective review of 158 patients with histologically confirmed CIN II-III who underwent LEEP between January 2011 and October 2012 was conducted. Post-treatment control was scheduled at the 3rd, 6th, 12th and 18th month. All patients were followed up by Pap smear and HR-HPV genotype and viral load testing. Results: Pre-treatment, HR-HPV DNA, was detected in all specimens of the patients. At follow-up, 25 patients were diagnosed as the residual/recurrent disease during the FU visit, among whom, 16 patients with positive margin: 13 patients (52%) with HR-HPV DNA+/cytology+, 2 patients (8%) with HR-HPV DNA+/cytology-, 1 patient (4%) with cytology+/HR-HPV DNA-; 9 patients with clean margin - 5 patients (55.6%) with HR-HPV DNA+/cytology+; 2 patients (22.2%) with HRHPV DNA+/cytology-, 2 patients (22.2%) with cytology+/HR-HPV DNA-. None of them persisting HR-HPV DNA-/cytology-with positive or negative margin was identified as the residual/recurrent disease. The majority of residual/recurrent disease was detected at the 12th and 18th month FU, and there was almost no difference in the sensitivity and negative predictive value (NPV) between at the 3rd month and the 6th month FU visits. 14 residual/recurrence disease (14/46:30.4%) had pre-treatment high viral load (>5 000 RUL/PC) and 11 (11/112, 9.8%) with pre-treatment low viral load, P<0.05. Conclusions: (1) The persistence HR-HPV DNA is the root cause of the residual/recurrent disease for the women treated for high-grade CIN; the pre-treatment viral load and margin can be seen as the predictor. (2) The FU visit beginning at the 6th month post-treatment and lasting at least 24 months with the combination of cytology and HPV testing. (3) Patients with high pre-treatment HPV load, which is considered as one risk of developing the residual/recurrent disease, should be paid more attention (especially above 500RUL/PC) to by clinicians.

Keywords

References

  1. Alonso I, Torne A , Puig-Tintore LM, et al (2006). Pre- and post-conization high-risk HPV testing predicts residual/ recurrent disease in patients treated for CIN 2-3. Gynecol Oncol, 103, 631-6. https://doi.org/10.1016/j.ygyno.2006.04.016
  2. Bar-Am A, Gamzu R, Levin I, et al (2003). Follow-up by combined cytology and human papillomavirus testing for patients post-cone biopsy: results of a long-term follow-up. Gynecol Oncol, 91, 149-53. https://doi.org/10.1016/S0090-8258(03)00435-9
  3. Barron BA, Fischetti VA, Zabriskie JB (1970). Studies of the bacteriophage kinetics of multicellular systems: a statistical model for the estimation of burst size per cell in streptococci. J Appl Bacteriol, 33, 436-42. https://doi.org/10.1111/j.1365-2672.1970.tb02216.x
  4. Bosch X, Manos MM, Munoz N, et al (1995). Prevalence of human papillomavirus in cervical cancer : a woldwide perspective. J Natl Cancer Inst, 87, 796-802. https://doi.org/10.1093/jnci/87.11.796
  5. Colgan TJ, Percy ME, Suri M, et al (1989). Human papillomavirus infection of morphologically normal cervical epithelium adjacent to squamous dysplasia and invasive carcinoma. Hum Patho, 20, 316-9. https://doi.org/10.1016/0046-8177(89)90039-7
  6. Costa S, De Simone P, Venturoli S, et al (2003). Factors predicting human papillomavirus clearance in cervical intraepithelial neoplasia lesions treated by conization. Gynecol Oncol, 90, 358-65. https://doi.org/10.1016/S0090-8258(03)00268-3
  7. Cuzick J, Beverley E, Ho L, et al (1999). HPV testing in primary screening of older women. Br J Cancer, 81, 554-8. https://doi.org/10.1038/sj.bjc.6690730
  8. Dalstein V, Riethmuller D, Sautiere JL, et al (2005). Detection of cervical precancer and cancer in a hospital population; benefits of testing for human papillomavirus. Eur J Cancer, 40, 1225-32.
  9. Du LB, Li HZ, Wang XH, et al (2014). Analysis of cancer incidence in Zhejiang cancer registry in China during 2000 to 2009. Asian Pac J Cancer Prev, 15, 5839-43. https://doi.org/10.7314/APJCP.2014.15.14.5839
  10. Felix JC, Muderspach LI, Duggan BD, et al (1994). The significance of positive margins in loop electrosurgical cone biopsies. Obstet Gynecol, 84, 996-1000.
  11. Flannelly G, Bolger B, Fawzi H, et al (2001). Follow up after LLETZ: could schedules be modified according to risk of recurrence? BJOG, 108, 1025-30.
  12. Gardeil F, Turner MJ (1997). A study of treatment failures following large loop excision of the transformation zone for the treatment of cervical intraepithelial neoplasia. Br J Obstet Gynaecol, 104, 1325. https://doi.org/10.1111/j.1471-0528.1997.tb10985.x
  13. Hanau CA, Bibbo M (1997). The case for cytologic follow-up after LEEP. Acta Cytol, 41, 731-6. https://doi.org/10.1159/000332695
  14. Hoskins WJ, Bundy BN, Thigpen JT, et al (1992). The influence of cytoreductive surgery on recurrence-free interval and survival in small-volume stage III epithelial ovarian cancer: a gynecologic oncology group study. Gynecol Oncol, 47, 159-66. https://doi.org/10.1016/0090-8258(92)90100-W
  15. Houfflin Debarge V, Collinet P, Vinatier D, et al (2003). Value of human papillomavirus testing after conization by loop electrosurgical excision for high-grade squamous intraepithelial lesions. Gynecol Oncol, 90, 587-92 https://doi.org/10.1016/S0090-8258(03)00372-X
  16. Jakus S, Edmonds PDunton CKing SA (2000). Margin status and excision of cervical intraepithelial neoplasia: a review. Obstet Gynecol Surv, 55, 520-7. https://doi.org/10.1097/00006254-200008000-00025
  17. Kang SB, Roh JW, Kim JW, et al (2001). A comparison of the therapeutic efficacies of large loop excision of the transformation zone and hysterectomy for the treatment of cervical intraepithelial neoplasia III. Int J Gynecol Cancer, 11, 387-91. https://doi.org/10.1046/j.1525-1438.2001.01054.x
  18. Kulmala SM, Kulmala SM, Syrjanen S, et al (2004). Human papillomavirus testing with the hybrid capture 2 assay and PCR as screening tools. J Clin Microbiol, 42, 2470-5. https://doi.org/10.1128/JCM.42.6.2470-2475.2004
  19. Li PL, Tan HZ (2015). Expression of $PPAR_{\gamma}$, p27 and Ki67 in cervical cancer and its clinical significance. J Int Transl Med, 3, 513-9.
  20. Macnab JC, Walkinshaw SA, Cordiner JW, et al (1986). Human papillomavirus in clinically and histologically normal tissue of patients with genital cancer. N Engl J Med, 315, 1052-8. https://doi.org/10.1056/NEJM198610233151703
  21. Meisels A, Begin R, Schneider V (1977). Dysplasias of uterine cervix: epidemiological aspects: role of age at first coitus and use of oral contraceptives. Cancer, 40, 3076-81. https://doi.org/10.1002/1097-0142(197712)40:6<3076::AID-CNCR2820400647>3.0.CO;2-U
  22. Munoz N, Bosch FX, de Sanjose S, et al (1992). The causal link between human papillomavirus and invasive cervical cancer: a population-based case-control study in Colombia and Spain. Int J Cancer, 52, 743-9. https://doi.org/10.1002/ijc.2910520513
  23. Murdoch JB, Morgan PR, Lopes A, et al (1992). Histological incomplete excision of CIN after large loop excision of the transformation zone (LLETZ) merits careful follow up, not retreatment. Br J Obstet Gynaecol, 99, 990-3. https://doi.org/10.1111/j.1471-0528.1992.tb13704.x
  24. Nagai Y, Maehama T, Asato T, et al (2000). Persistence of human papillomavirus infection after therapeutic conization for CIN 3: is it an alarm for disease recurrence? Gynecol Oncol, 79, 294-9. https://doi.org/10.1006/gyno.2000.5952
  25. Nobbenhuis MA, Meijer CJ, van den Brule AJ, et al (2001). Addition of high-risk HPV testing improves the current guidelines on follow-up after treatment for cervical intraepithelial neoplasia. Br J Cancer, 84, 796-801. https://doi.org/10.1054/bjoc.2000.1689
  26. Paraskevaidis E, Koliopoulos G, Malamou-Mitsi V, et al (2001). Large loop excision of the transformation zone for treating cervical intraepithelial neoplasia: a 12-year experience. Anticancer Res, 21, 3097-9.
  27. Pinto AP, Crum CP (2000). Natural history of cervical neoplasia: defining progression and its consequence. Clin Obstet Gynecol, 43, 352-62. https://doi.org/10.1097/00003081-200006000-00015
  28. Prendiville W, Cullimore J, Norman S (1989). Large loop excision of the transformation zone (LLETZ). A new method of management for women with cervical intraepithelial neoplasia. Br J Obstet Gynaecol, 96, 1054-60. https://doi.org/10.1111/j.1471-0528.1989.tb03380.x
  29. Pretet JL, Dalstein V, Monnier-Benoit S, et al (2004). High risk HPV load estimated by Hybrid Capture II correlates with HPV16 load measured by real-time PCR in cervical smears of HPV16-infected women. J Clin Virol, 31, 140-7. https://doi.org/10.1016/j.jcv.2004.02.008
  30. Quinn M, Babb P, Jones J, et al (1999). Effect of screening on incidence of and mortality from cancer of cervix in England: evaluation based on routinely collected statistics. BMJ, 318, 904-8. https://doi.org/10.1136/bmj.318.7188.904
  31. Riethmuller D, Gay C, Bertrand X, et al (1999). Genital human papillomavirus infection among women recruited for routine cervical cancer screening or for colposcopy determined by Hybrid Capture II and polymerase chain reaction. Diagn Mol Pathol, 8, 157-64. https://doi.org/10.1097/00019606-199909000-00009
  32. Sarian LO, Derchain SF, Andrade LA, et al (2004). 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, 94, 181-6. https://doi.org/10.1016/j.ygyno.2004.03.036
  33. Shen XR, Feng R, Chai J, et al (2014). Modeling age-specific cancer incidences using logistic growth equations: implications for data collection. Asian Pac J Cancer Prev, 15, 9731-7. https://doi.org/10.7314/APJCP.2014.15.22.9731
  34. Song SH, Lee JK, Oh MJ, et al (2006). Persistent HPV infection after conization in patients with negative margins. Gynecol Oncol, 101, 418-22. https://doi.org/10.1016/j.ygyno.2005.10.028
  35. Tangtrakul S, Linasmita V, Israngura N, et al (2002). Detection of residual disease by cytology in patients with cervical intraepithelial neoplasia III post-large loop excision of the transformation zone. J Obstet Gynaecol Res, 28, 95-8. https://doi.org/10.1046/j.1341-8076.2002.00014.x
  36. Valasoulis G, Stasinou SM, Nasioutziki M, et al (2014). Expression of HPV-related biomarkers and grade of cervical intraepithelial lesion at treatment. Acta Obstet Gynecol Scand, 93, 194-200. https://doi.org/10.1111/aogs.12298
  37. Wang Y, Yu YH, Shen K, et al (2014). Cervical cancer screening and analysis of potential risk factors in 43, 567 women in Zhongshan, China. Asian Pac J Cancer Prev, 15, 671-6. https://doi.org/10.7314/APJCP.2014.15.2.671
  38. Zhang B, Zhou AF, Zhu CC, et al (2014). Risk factors for cervical cancer in rural areas of Wuhan China: a matched case-control study. Asian Pac J Cancer Prev, 14, 7595-600.
  39. Zielinski GD, Rozendaal L, Voorhorst FJ, et al (2003). HPV testing can reduce the number of follow-up visits in women treated for cervical intraepithelial neoplasia grade 3. Gynecol Oncol, 91, 67-73. https://doi.org/10.1016/S0090-8258(03)00415-3

Cited by

  1. miR-23b as a potential tumor suppressor and its regulation by DNA methylation in cervical cancer vol.10, pp.1, 2015, https://doi.org/10.1186/s13027-015-0037-6
  2. Incisal margin condition after LEEP for cervical intraepithelial neoplasia patients and prognosis vol.12, pp.2, 2016, https://doi.org/10.3892/etm.2016.3338