Cold knife conization (CKC) is a diagnostic excisional procedure for the removal of high grade cervical dysplasia, both cervical intraepithelial neoplasia (CIN) on the outer part of the cervix and adenocarcinoma in situ (AIS) in the column of gland cells that line the cervical canal.1,2 Using a scalpel, a circumferential incision is made to excise the portion of both the outer and inner cervix containing abnormal tissue. Local application of vasoconstrictive solution helps minimize blood loss during the procedure.3 If there is bleeding, the surgeon may use sutures or electrocautery for hemostasis. Additionally, a piece of rolled gauze dipped in ferric subsulfate solution known as Monsel’s solution or paste may be packed into the biopsy site to reduce perioperative blood loss and cramping. The removed specimen is sent to a pathology laboratory for further analysis.
CKC requires either regional or general anesthesia and is done in an operating room. A colposcopic exam may be done immediately preceding the procedure to help the surgeon decide on the size and shape of the cone biopsy. Patients usually go home on the same day of the procedure or the next morning.
Following a CKC, patients may experience some lower abdominal and pelvic pain and may have bloody vaginal discharge for 7-10 days followed by yellowish discharge for up to one month.1 Fever, foul-smelling discharge, heavy vaginal bleeding (>1 pad in an hour or passing clots) are not expected and should prompt evaluation.
Patients should avoid intercourse, placing anything in the vagina, or immersing in water for 2-4 weeks. Patients are typically scheduled for a follow-up visit a few weeks after the procedure to ensure appropriate healing and to review histopathological results. The final pathology report is used to determine appropriate follow-up.
High Grade CIN
American Society for Colposcopy and Cervical Pathology (ASCCP) clinical practice guidelines recommend that if colposcopic biopsy results return with high grade CIN, all nonpregnant patients 25 and older receive treatment.2 Treatment aims to destroy or remove pre-cancerous areas of the cervix. For nonpregnant patients of all ages with CIN 3, they warn that observation alone is unacceptable. Excisional treatment (loop electrosurgical excision procedure [LEEP], CKC, or laser cone biopsy) is preferred, although ablation (including cryotherapy, laser ablation, and thermoablation) is acceptable under certain circumstances (lesion does not extend into the canal and covers less than 75% of the surface area of the ectocervix). Hysterectomy is unacceptable as a sole treatment.
For patients with CIN 2, observation is acceptable for those who are concerned about the effects of treatment on future pregnancy outcomes.2 For patients younger than 25 with CIN 2, observation is recommended, although treatment is also acceptable. Observation includes colposcopy and HPV testing at six and 12 months. If the lesion persists, surveillance at 6-month intervals should be continued for an additional year. If the lesion persists after two years of observation, a diagnostic excisional procedure is recommended. Conversely, if two consecutive evaluations indicate disease regression, HPV testing can be done annually. If test results continue to return negative for three years, HPV testing can be moved to three-year intervals for at least 25 years.
AIS
If colposcopy results confirm a diagnosis of AIS, a diagnostic excisional procedure such as CKC or LEEP is recommended for all patients regardless of pregnancy status, followed by a hysterectomy, the timing of which depends on the patient’s desire to preserve fertility. A diagnostic excisional procedure is recommended even when a hysterectomy is planned in order to rule out invasive adenocarcinoma, which may require further or different treatment.
If negative margins are not achieved on the first excision, a repeat excisional procedure is recommended if deemed safe and feasible.2,4 Once negative margins are achieved or repeat excisional procedures are no longer feasible, a simple hysterectomy is recommended. If negative margins could not be achieved, a simple or modified radical hysterectomy is acceptable. Hysterectomy is recommended even when negative margins are achieved due to the risk of recurrent AIS and development of invasive cancer, even with negative margins. A 2001 meta-analysis synthesized findings from 14 studies and found that even among those who achieved negative margins (n=147), 26% of patients had residual disease.6 They also found that among patients treated only with an excisional procedure and follow-up testing in order to maintain fertility (n=297), 9% suffered disease recurrence.
For patients who desire to preserve fertility, if the excisional procedure successfully removes the dysplastic tissue, guidelines recommend surveillance with Pap smears, HPV co-testing, and endocervical sampling every six months for three years, then annually until a simple hysterectomy can be performed.2,4 If co-testing and endocervical sampling are consistently negative during the first five years, foregoing a hysterectomy and instead continuing to test every three years indefinitely is considered acceptable. The risks and benefits of fertility-preserving treatment should be discussed with the patient.
Following hysterectomy, guidelines recommend continued long-term monitoring and testing, starting with HPV or contesting six months after treatment and continuing annually. If any tests return positive, colposcopy and appropriate biopsies are recommended. Once three consecutive tests have returned negative results, testing can continue every three years for at least 25 years, even past the age of 65 as long as the patient is in reasonably good health.
References
- WHO Guidelines Approved by the Guidelines Review Committee. Comprehensive Cervical Cancer Control: A Guide to Essential Practice. World Health Organization; Copyright © World Health Organization 2014.; 2014.
- Perkins RB, Guido RS, Castle PE, et al. 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors. J Low Genit Tract Dis. Apr 2020;24(2):102-131. doi:10.1097/LGT.0000000000000525
- Martin-Hirsch PL, Kitchener H. Interventions for preventing blood loss during the treatment of cervical intraepithelial neoplasia. Cochrane Database Syst Rev. 2000;(2):CD001421. doi:10.1002/14651858.CD001421
- Teoh D, Musa F, Salani R, Huh W, Jimenez E. Diagnosis and Management of Adenocarcinoma in Situ: A Society of Gynecologic Oncology Evidence-Based Review and Recommendations. Obstet Gynecol. Apr 2020;135(4):869-878. doi:10.1097/AOG.0000000000003761
- Jiang Y, Chen C, Li L. Comparison of Cold-Knife Conization versus Loop Electrosurgical Excision for Cervical Adenocarcinoma In Situ (ACIS): A Systematic Review and Meta-Analysis. PLoS One. 2017;12(1):e0170587. doi:10.1371/journal.pone.0170587
- Krivak TC, Rose GS, McBroom JW, Carlson JW, Winter WE, 3rd, Kost ER. Cervical adenocarcinoma in situ: a systematic review of therapeutic options and predictors of persistent or recurrent disease. Obstet Gynecol Surv. Sep 2001;56(9):567-75. doi:10.1097/00006254-200109000-00023
