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Cervical intraepithelial neoplasia: Treatment and follow-up

Jason D Wright, MD
Section Editor
Barbara Goff, MD
Deputy Editor
Sandy J Falk, MD, FACOG


Cervical intraepithelial neoplasia (CIN) is a premalignant condition of the uterine cervix [1]. The ectocervix (surface of the cervix that is visualized on vaginal speculum examination) is covered in squamous epithelium, and the endocervix, including the cervical canal, is covered with glandular epithelium. CIN refers to squamous abnormalities. Glandular cervical neoplasia includes adenocarcinoma in situ and adenocarcinoma. (See "Cervical cytology: Evaluation of atypical and malignant glandular cells" and "Cervical adenocarcinoma in situ" and "Invasive cervical adenocarcinoma".)

Screening tests for cervical cancer include cervical cytology and testing for oncogenic subtypes of human papillomavirus (table 1). Follow-up of abnormalities in screening tests with colposcopy and cervical biopsy may result in a diagnosis of CIN, glandular neoplasia, or cervical cancer [2].

CIN may be low grade (CIN 1) or high grade (CIN 2,3). Women with low-grade CIN have a low potential for developing cervical malignancy, while those with high-grade lesions are at higher risk of progression to malignancy. In managing women with CIN, the goal is to prevent possible progression to invasive cancer while avoiding overtreatment of lesions that are likely to regress.

Choosing a treatment option for CIN and follow-up after treatment is reviewed here. Evaluation and management of low-grade and high-grade CIN is discussed separately. (See "Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions".)

Other related issues include:


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Literature review current through: Sep 2016. | This topic last updated: Jul 11, 2016.
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  1. Montz FJ. Management of high-grade cervical intraepithelial neoplasia and low-grade squamous intraepithelial lesion and potential complications. Clin Obstet Gynecol 2000; 43:394.
  2. Massad LS, Einstein MH, Huh WK, et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis 2013; 17:S1.
  3. Martin-Hirsch PP, Paraskevaidis E, Bryant A, Dickinson HO. Surgery for cervical intraepithelial neoplasia. Cochrane Database Syst Rev 2013; :CD001318.
  4. Paraskevaidis E, Arbyn M, Sotiriadis A, et al. The role of HPV DNA testing in the follow-up period after treatment for CIN: a systematic review of the literature. Cancer Treat Rev 2004; 30:205.
  5. Chirenje ZM, Rusakaniko S, Akino V, Mlingo M. A randomised clinical trial of loop electrosurgical excision procedure (LEEP) versus cryotherapy in the treatment of cervical intraepithelial neoplasia. J Obstet Gynaecol 2001; 21:617.
  6. Ferenczy A, Choukroun D, Arseneau J. Loop electrosurgical excision procedure for squamous intraepithelial lesions of the cervix: advantages and potential pitfalls. Obstet Gynecol 1996; 87:332.
  7. Pearson SE, Whittaker J, Ireland D, Monaghan JM. Invasive cancer of the cervix after laser treatment. Br J Obstet Gynaecol 1989; 96:486.
  8. Yamaguchi S, Tsuda H, Takemori M, et al. Photodynamic therapy for cervical intraepithelial neoplasia. Oncology 2005; 69:110.
  9. Bodner K, Bodner-Adler B, Wierrani F, et al. Cold-knife conization versus photodynamic therapy with topical 5-aminolevulinic acid (5-ALA) in cervical intraepithelial neoplasia (CIN) II with associated human papillomavirus infection: a comparison of preliminary results. Anticancer Res 2003; 23:1785.
  10. Hefler LA, Grimm C, Speiser P, et al. The cyclooxygenase-2 inhibitor rofecoxib (Vioxx) in the treatment of cervical dysplasia grade II-III A phase II trial. Eur J Obstet Gynecol Reprod Biol 2006; 125:251.
  11. Garcia F, Petry KU, Muderspach L, et al. ZYC101a for treatment of high-grade cervical intraepithelial neoplasia: a randomized controlled trial. Obstet Gynecol 2004; 103:317.
  12. Velema JP, Ferrera A, Figueroa M, et al. Burning wood in the kitchen increases the risk of cervical neoplasia in HPV-infected women in Honduras. Int J Cancer 2002; 97:536.
  13. Vlastos AT, West LA, Atkinson EN, et al. Results of a phase II double-blinded randomized clinical trial of difluoromethylornithine for cervical intraepithelial neoplasia grades 2 to 3. Clin Cancer Res 2005; 11:390.
  14. Ruffin MT, Bailey JM, Normolle DP, et al. Low-dose topical delivery of all-trans retinoic acid for cervical intraepithelial neoplasia II and III. Cancer Epidemiol Biomarkers Prev 2004; 13:2148.
  15. Van Pachterbeke C, Bucella D, Rozenberg S, et al. Topical treatment of CIN 2+ by cidofovir: results of a phase II, double-blind, prospective, placebo-controlled study. Gynecol Oncol 2009; 115:69.
  16. Geisler S, Speiser S, Speiser L, et al. Short-Term Efficacy of Trichloroacetic Acid in the Treatment of Cervical Intraepithelial Neoplasia. Obstet Gynecol 2016; 127:353.
  17. Del Priore G, Gudipudi DK, Montemarano N, et al. Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervical dysplasia. Gynecol Oncol 2010; 116:464.
  18. Soutter WP, de Barros Lopes A, Fletcher A, et al. Invasive cervical cancer after conservative therapy for cervical intraepithelial neoplasia. Lancet 1997; 349:978.
  19. Jakobsson M, Gissler M, Paavonen J, Tapper AM. Long-term mortality in women treated for cervical intraepithelial neoplasia. BJOG 2009; 116:838.
  20. Kalliala I, Anttila A, Pukkala E, Nieminen P. Risk of cervical and other cancers after treatment of cervical intraepithelial neoplasia: retrospective cohort study. BMJ 2005; 331:1183.
  21. 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.
  22. Wang SS, Sherman ME, Hildesheim A, et al. Cervical adenocarcinoma and squamous cell carcinoma incidence trends among white women and black women in the United States for 1976-2000. Cancer 2004; 100:1035.
  23. Strander B, Andersson-Ellström A, Milsom I, Sparén P. Long term risk of invasive cancer after treatment for cervical intraepithelial neoplasia grade 3: population based cohort study. BMJ 2007; 335:1077.
  24. Melnikow J, McGahan C, Sawaya GF, et al. Cervical intraepithelial neoplasia outcomes after treatment: long-term follow-up from the British Columbia Cohort Study. J Natl Cancer Inst 2009; 101:721.
  25. Rebolj M, Helmerhorst T, Habbema D, et al. Risk of cervical cancer after completed post-treatment follow-up of cervical intraepithelial neoplasia: population based cohort study. BMJ 2012; 345:e6855.
  26. Mitchell MF, Tortolero-Luna G, Cook E, et al. 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.
  27. Demopoulos RI, Horowitz LF, Vamvakas EC. Endocervical gland involvement by cervical intraepithelial neoplasia grade III. Predictive value for residual and/or recurrent disease. Cancer 1991; 68:1932.
  28. 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.
  29. Manchanda R, Baldwin P, Crawford R, et al. Effect of margin status on cervical intraepithelial neoplasia recurrence following LLETZ in women over 50 years. BJOG 2008; 115:1238.
  30. Gök M, Coupé VM, Berkhof J, et al. HPV16 and increased risk of recurrence after treatment for CIN. Gynecol Oncol 2007; 104:273.
  31. Paraskevaidis E, Koliopoulos G, Alamanos Y, et al. Human papillomavirus testing and the outcome of treatment for cervical intraepithelial neoplasia. Obstet Gynecol 2001; 98:833.
  32. 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.
  33. Chua KL, Hjerpe A. Human papillomavirus analysis as a prognostic marker following conization of the cervix uteri. Gynecol Oncol 1997; 66:108.
  34. Nobbenhuis MA, Meijer CJ, van den Brule AJ, et al. Addition of high-risk HPV testing improves the current guidelines on follow-up after treatment for cervical intraepithelial neoplasia. Br J Cancer 2001; 84:796.
  35. Kaufman RH. Is there a role for human papillomavirus testing in clinical practice? Obstet Gynecol 2001; 98:724.
  36. Reich O, Pickel H, Lahousen M, et al. Cervical intraepithelial neoplasia III: long-term outcome after cold-knife conization with clear margins. Obstet Gynecol 2001; 97:428.
  37. Paterson-Brown S, Chappatte OA, Clark SK, et al. The significance of cone biopsy resection margins. Gynecol Oncol 1992; 46:182.
  38. Felix JC, Muderspach LI, Duggan BD, Roman LD. The significance of positive margins in loop electrosurgical cone biopsies. Obstet Gynecol 1994; 84:996.
  39. Park JY, Lee SM, Yoo CW, et al. Risk factors predicting residual disease in subsequent hysterectomy following conization for cervical intraepithelial neoplasia (CIN) III and microinvasive cervical cancer. Gynecol Oncol 2007; 107:39.
  40. Mohamed-Noor K, Quinn MA, Tan J. Outcomes after cervical cold knife conization with complete and incomplete excision of abnormal epithelium: a review of 699 cases. Gynecol Oncol 1997; 67:34.
  41. Husseinzadeh N, Shbaro I, Wesseler T. Predictive value of cone margins and post-cone endocervical curettage with residual disease in subsequent hysterectomy. Gynecol Oncol 1989; 33:198.
  42. Lapaquette TK, Dinh TV, Hannigan EV, et al. Management of patients with positive margins after cervical conization. Obstet Gynecol 1993; 82:440.
  43. Livasy CA, Maygarden SJ, Rajaratnam CT, Novotny DB. Predictors of recurrent dysplasia after a cervical loop electrocautery excision procedure for CIN-3: a study of margin, endocervical gland, and quadrant involvement. Mod Pathol 1999; 12:233.
  44. Phelps JY 3rd, Ward JA, Szigeti J 2nd, et al. Cervical cone margins as a predictor for residual dysplasia in post-cone hysterectomy specimens. Obstet Gynecol 1994; 84:128.
  45. Lopes A, Morgan P, Murdoch J, et al. The case for conservative management of "incomplete excision" of CIN after laser conization. Gynecol Oncol 1993; 49:247.
  46. Maluf PJ, Adad SJ, Murta EF. Outcome after conization for cervical intraepithelial neoplasia grade III: relation with surgical margins, extension to the crypts and mitoses. Tumori 2004; 90:473.
  47. Moore BC, Higgins RV, Laurent SL, et al. Predictive factors from cold knife conization for residual cervical intraepithelial neoplasia in subsequent hysterectomy. Am J Obstet Gynecol 1995; 173:361.
  48. Kalogirou D, Antoniou G, Karakitsos P, et al. Predictive factors used to justify hysterectomy after loop conization: increasing age and severity of disease. Eur J Gynaecol Oncol 1997; 18:113.
  49. Reich O, Lahousen M, Pickel H, et al. Cervical intraepithelial neoplasia III: long-term follow-up after cold-knife conization with involved margins. Obstet Gynecol 2002; 99:193.
  50. Livasy CA, Moore DT, Van Le L. The clinical significance of a negative loop electrosurgical cone biopsy for high-grade dysplasia. Obstet Gynecol 2004; 104:250.
  51. http://www.asccp.org/ (Accessed on March 22, 2012).
  52. Murdoch JB, Morgan PR, Lopes A, Monaghan JM. Histological incomplete excision of CIN after large loop excision of the transformation zone (LLETZ) merits careful follow up, not retreatment. Br J Obstet Gynaecol 1992; 99:990.
  53. Monk A, Pushkin SF, Nelson AL, Gunning JE. Conservative management of options for patients with dysplasia involving endocervical margins of cervical cone biopsy specimens. Am J Obstet Gynecol 1996; 174:1695.
  54. Buxton EJ, Luesley DM, Wade-Evans T, Jordan JA. Residual disease after cone biopsy: completeness of excision and follow-up cytology as predictive factors. Obstet Gynecol 1987; 70:529.
  55. Wright TC Jr, Massad LS, Dunton CJ, 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.
  56. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin number 66, September 2005. Management of abnormal cervical cytology and histology. Obstet Gynecol 2005; 106:645.
  57. Zielinski GD, Bais AG, Helmerhorst TJ, et al. HPV testing and monitoring of women after treatment of CIN 3: review of the literature and meta-analysis. Obstet Gynecol Surv 2004; 59:543.
  58. Zielinski GD, Rozendaal L, Voorhorst FJ, 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.
  59. Chao A, Lin CT, Hsueh S, et al. Usefulness of human papillomavirus testing in the follow-up of patients with high-grade cervical intraepithelial neoplasia after conization. Am J Obstet Gynecol 2004; 190:1046.
  60. Houfflin Debarge V, Collinet P, Vinatier D, et al. Value of human papillomavirus testing after conization by loop electrosurgical excision for high-grade squamous intraepithelial lesions. Gynecol Oncol 2003; 90:587.
  61. Coupé VM, Berkhof J, Verheijen RH, Meijer CJ. Cost-effectiveness of human papillomavirus testing after treatment for cervical intraepithelial neoplasia. BJOG 2007; 114:416.
  62. Park JY, Kim DY, Kim JH, et al. Human papillomavirus test after conization in predicting residual disease in subsequent hysterectomy specimens. Obstet Gynecol 2009; 114:87.
  63. Kocken M, Helmerhorst TJ, Berkhof J, et al. Risk of recurrent high-grade cervical intraepithelial neoplasia after successful treatment: a long-term multi-cohort study. Lancet Oncol 2011; 12:441.
  64. Committee on Practice Bulletins—Gynecology. ACOG Practice Bulletin Number 131: Screening for cervical cancer. Obstet Gynecol 2012; 120:1222.
  65. Saslow D, Solomon D, Lawson HW, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J Clin 2012; 62:147.
  66. Singhal R, Rubenstein LV, Wang M, et al. Variations in practice guideline adherence for abnormal cervical cytology in a county healthcare system. J Gen Intern Med 2008; 23:575.
  67. Saslow D, Runowicz CD, Solomon D, et al. American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA Cancer J Clin 2002; 52:342.
  68. US Preventive Services Task Force. Screening for cervical cancer: recommendations and rationale. Agency for Healthcare Research and Quality, Rockville, MD 2003. www.ahrq.gov/clinic/3rduspstf/cervcan/cervcanrr.pdf (Accessed on October 11, 2011).
  69. Stokes-Lampard H, Wilson S, Waddell C, et al. Vaginal vault smears after hysterectomy for reasons other than malignancy: a systematic review of the literature. BJOG 2006; 113:1354.
  70. Schockaert S, Poppe W, Arbyn M, et al. Incidence of vaginal intraepithelial neoplasia after hysterectomy for cervical intraepithelial neoplasia: a retrospective study. Am J Obstet Gynecol 2008; 199:113.e1.
  71. Kang WD, Choi HS, Kim SM. Is vaccination with quadrivalent HPV vaccine after loop electrosurgical excision procedure effective in preventing recurrence in patients with high-grade cervical intraepithelial neoplasia (CIN2-3)? Gynecol Oncol 2013; 130:264.
  72. Bleeker MC, Hogewoning CJ, Berkhof J, et al. Concordance of specific human papillomavirus types in sex partners is more prevalent than would be expected by chance and is associated with increased viral loads. Clin Infect Dis 2005; 41:612.
  73. Aynaud O, Ionesco M, Barrasso R. Penile intraepithelial neoplasia. Specific clinical features correlate with histologic and virologic findings. Cancer 1994; 74:1762.
  74. Barrasso R, De Brux J, Croissant O, Orth G. High prevalence of papillomavirus-associated penile intraepithelial neoplasia in sexual partners of women with cervical intraepithelial neoplasia. N Engl J Med 1987; 317:916.
  75. Hogewoning CJ, Bleeker MC, van den Brule AJ, et al. Condom use promotes regression of cervical intraepithelial neoplasia and clearance of human papillomavirus: a randomized clinical trial. Int J Cancer 2003; 107:811.
  76. Bleeker MC, Hogewoning CJ, Voorhorst FJ, et al. Condom use promotes regression of human papillomavirus-associated penile lesions in male sexual partners of women with cervical intraepithelial neoplasia. Int J Cancer 2003; 107:804.
  77. Marrazzo JM, Koutsky LA, Kiviat NB, et al. Papanicolaou test screening and prevalence of genital human papillomavirus among women who have sex with women. Am J Public Health 2001; 91:947.
  78. Marrazzo JM, Koutsky LA, Stine KL, et al. Genital human papillomavirus infection in women who have sex with women. J Infect Dis 1998; 178:1604.