Conization of Cervix
Conization of the cervix is defined as excision of a cone-shaped or cylindrical wedge from the cervix uteri that includes the transformation zone and all or a portion of the endocervical canal. It is used for the definitive diagnosis of squamous or glandular intraepithelial lesions, for excluding microinvasive carcinomas, and for conservative treatment of cervical intraepithelial neoplasia (CIN).
While no recent changes have occurred in the technique of conization, a quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine (Gardasil) was introduced in 2006. Its widespread use is expected to reduce the number of cervical neoplasias, and, consequently the need for surgical interventions.
Conization can be performed with a scalpel (cold-knife conization), laser, or electrosurgical loop. The latter is called the loop electrosurgical excision procedure (LEEP) or large loop excision of the transformation zone (LLETZ). Combined conization usually refers to a procedure started with a laser and completed with a cold-knife technique. Laser conization can be excisional or destructive (by vaporization). Techniques for diagnostic and therapeutic conization are virtually identical. The extent of excision must be adjusted according to individual needs (see image below).
Each of these approaches has distinct benefits and disadvantages. Cold-knife conization provides the cleanest specimen margins for further histologic study, but it is typically associated with more bleeding than laser or LEEP, and it requires general anesthesia in most cases. Laser procedures are of longer duration and, especially if low-power density is used, may “burn” the margins, thus interfering with histologic diagnosis. The main advantage with this procedure is that dots produced by the laser energy can be used to accurately outline the exocervical margins. However, overall, the benefit of using laser for conization may not justify the high cost of the procedure.
LEEP procedures have several advantages, including rapidity, preservation of the margins for histologic evaluation, and virtual bloodlessness. Moreover, one can perform LEEP procedures in the office or in other outpatient settings.
Procedures that do not yield tissue for pathologic studies, such as electrocoagulation or cryosurgery, are not discussed in this article.
Procedures similar to conization were used in the early 19th century in an attempt to excise gross cervical tumors per vaginam. During the second half of the 20th century, conization evolved as an important tool for diagnosing the cause of positive cervical cytology in women without visible lesions and, later, as treatment of CIN. The diagnostic application of cold-knife conization was reduced following the widespread use of colposcopically directed cervical biopsies combined with endocervical curettage. However, conization remains an important diagnostic tool in selected situations. Therapeutic conization for CIN became an accepted modality in the management of CIN following publication of rigorous studies by Scandinavian and Austrian researchers. [1, 2, 3, 4] The precise origin of cold-knife conization is historically uncertain.
The incidence and mortality of carcinoma of the cervix have declined about 300% since the 1930s in most of North America and in Europe. The sharpest decline began in the 1950s, following the introduction of cytologic screening. Since cytology rarely provides precise diagnosis, conization of the cervix became an important tool for the determination of the accurate diagnosis of abnormal, cytologic, clinical, or colposcopic lesions. Additionally, it is a major method for the treatment of intraepithelial cervical lesions.
The frequency with which conization procedures are performed depends on the number of suggested or detected cases of CIN and can only be estimated. Approximately 10-20 million cases of human papillomavirus (HPV) infection may be responsible for causing CIN or cervical carcinoma. Although a large proportion of these (an estimated 80%) regress spontaneously, for a definitive diagnosis or treatment, detected cases require colposcopy and, at times, conization. In the United States, 10,370 new cases of cancer of the cervix (uterus) and 3,710 deaths from this disease were estimated for 2005.
Worldwide, cervical carcinoma is the third most common cause of cancer-induced death in women; 470,606 new cases and 233,372 deaths were reported in the late 1970s. It remains a major cause of mortality in regions without effective universal screening programs, particularly in developing countries.
Intraepithal neoplasia is induced by high-risk human papillomavirus infection. Types 16 and 18 are found in 50-80% of squamous intraepithelial lesions (SIL) and in up to 90% of invasive cancers. 
Human papillomavirus infection induces proliferation and atypia in the cervical epithelium. Most commonly, these changes occur in the transformation zone, or, at times, directly in the squamous or in the glandular epithelium.
The clinical diagnostic process usually begins by a pelvic examination and by taking a Papanicolaou smear. Suspicious lesions are biopsied, preferably under colposcopic control. Diagnostic conizations are performed if colposcopic biopsies require further evaluation. Therapeutic conizations are indicated if SILs (in particular HSIL) are detected.
Diagnostic conization is indicated in the following situations:
Finding epithelial cell abnormalities, in particular high-grade squamous intraepithelial lesions (HSIL) or low-grade squamous intraepithelial lesions (LSIL) in the absence of gross or colposcopic lesions of the cervix
Unsatisfactory colposcopy, defined as the examiner’s inability to view the entire transformation zone, including the squamocolumnar junction, in women with epithelial cell abnormalities
Uncertainty regarding the presence or absence of microinvasion or invasion following the diagnosis of CIN by directed biopsy
Finding CIN or microinvasive cancer during endocervical curettage
Cytologic or histologic evidence of premalignant or malignant glandular epithelium
Cytologic diagnosis inconsistent with histologic diagnosis based on directed biopsy findings
Therapeutic conization is currently the preferred modality to treat CIN grades 2 and 3. All described approaches (ie, cold-knife, laser, LEEP) are equally effective, as found by Mitchell and colleagues. 
Historically, carcinoma in situ (CIN grade 3), the first identified intraepithelial neoplasia, was treated with hysterectomy. During the last quarter of the 20th century, several large published series proved the effectiveness of the more conservative conization procedure. In 1976, Kolstad and Klem reported on 1122 patients with carcinoma in situ treated with conization, with a recurrence rate of 2.3% and an unexpected discovery of small invasive carcinomas in 0.9%.  Bjerre et al reported treatment failure in 7% of their patients who received therapeutic conization. 
Controversies exist as to the necessity of removing the entire endocervical canal, including the internal os, in all cases. This approach, recommended by at least 2 studies, may increase the risk of cervical incompetence in women who desire posttreatment pregnancy. The author believes that determining the probability of high endocervical involvement fairly accurately is possible by performing endocervical curettage or by obtaining cytology specimens with an endocervical brush. If the results of these tests are negative for CIN or glandular atypia and if the patient wishes to preserve her childbearing potential, the author preserves the cranial extremity of the endocervical canal.
In addition to conization, CIN can also be treated by hysterectomy or by other destructive methods, such as cryotherapy, laser vaporization conization, or radical electrocoagulation. The decision to use hysterectomy or conization is usually based on the grade and extent of the disease, the patient’s age, the desire for childbearing, and the history of recurrence after conservative management. Because destructive methods such as cryotherapy yield no specimen for histologic studies, their use should be limited to those women in whom an accurate preoperative diagnosis has been established by directed biopsy findings.
The cervix is typically 2.5 cm long. It communicates with the endometrial cavity of the corpus uteri through the internal os and with the vagina through the external os. The vaginal portion (also called exocervix or portio vaginalis) is covered by stratified squamous epithelium, and the cervical canal is covered by columnar epithelium, which also forms endocervical glands, more correctly called clefts. The 2 epithelia meet at the squamocolumnar junction. In most adult women, the squamocolumnar junction is not an abrupt meeting point, but a zone containing irregular areas of glandular and metaplastic squamous epithelium. The size of this transformation zone varies from 2-15 mm (see image below).
CIN usually arises in the transformation zone and usually extends to a depth of less than 7 mm. The blood supply of the cervix originates mainly from the cervical branches of the uterine artery and from branches of the vaginal and pudendal arteries.
Conization should be avoided during pregnancy if at all possible because it commonly causes significant (>500 mL) bleeding. Approximately 30% of pregnant patients who undergo conization develop delayed postoperative hemorrhage, and fetal loss has been reported in as many as 10%. Rare indications for performing this procedure include the possible presence of invasive cancer discovered during the first or second trimester.
Kolstad P, Klem V. Long-term followup of 1121 cases of carcinoma in situ. Obstet Gynecol. 1976 Aug. 48(2):125-9. [Medline].
Bjerre B, Eliasson G, Linell F, et al. Conization as only treatment of carcinoma in situ of the uterine cervix. Am J Obstet Gynecol. 1976 May 15. 125(2):143-52. [Medline].
Burghardt E. Die diagnostische Konisation der Portio Vaginalis Uteri. Geburtshilfe, Frauenheilunde. 1963. 23:1.
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 Mar. 97(3):428-30. [Medline].
Garcia AA, Hamid O, El-Khoueiry A. Cervical Cancer. Medscape Reference. Available at http://emedicine.medscape.com/article/253513-overview. Accessed: December 3, 2007.
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 Nov. 92(5):737-44. [Medline].
Kliemann LM, Silva M, Reinheimer M, Rivoire WA, Capp E, Dos Reis R. Minimal cold knife conization height for high-grade cervical squamous intraepithelial lesion treatment. Eur J Obstet Gynecol Reprod Biol. 2012 Sep 1. [Medline].
Bae HS, Chung YW, Kim T, Lee KW, Song JY. The appropriate cone depth to avoid endocervical margin involvement is dependent on age and disease severity. Acta Obstet Gynecol Scand. 2012 Oct 4. [Medline].
Felix JC, Muderspach LI, Duggan BD, Roman LD. The significance of positive margins in loop electrosurgical cone biopsies. Obstet Gynecol. 1994 Dec. 84(6):996-1000. [Medline].
Costa S, Negri G, Sideri M, Santini D, Martinelli G, Venturoli S, et al. Human papillomavirus (HPV) test and PAP smear as predictors of outcome inconservatively treated adenocarcinoma in situ (AIS) of the uterine cervix. Gynecol Oncol. 2007 Jul;106(1):170-6. July 2007. 106(1):170-6. [Medline].
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 Apr 18; [Epub ahead of print]. April 2007. [Medline].
Wun TH, Chiu WW,Wang CB et al. Age and prevalence of cervical carcinoma in subsequent hysterectomy following a conization procedure. Taiwan J Obstet Gynecol. Sep. 48-3:254-7. [Medline].
Noehr B, Frederiksen K,Tabor A et al. Loop electrosurgical excision of the cervix and risk for spontaneous preterm delivery in twin pregnancies. Obstet.Gynecol. Sep/2009. 114(3):511-5. [Medline].
Jacobson M, Gissler M, Paavonen J, Tapper AM. Loop electrosurgical excision procedure and the risk of preterm birth. Obstet. Gynecol. Sept 2009. 114(3):504-10. [Medline].
Roberta Z, Maria IM, Andrea T, Chiara D, Maria GD, Serena C, et al. Detection of Residual/Recurrent Cervical Disease after Successful LEEP Conization: the Possible Role of mRNA-HPV Test. Curr Pharm Des. 2012 Sep 24. [Medline].
Samson SL, Bentley JR, Fahey TJ, et al. The effect of loop electrosurgical excision procedure on future pregnancy outcome. Obstet Gynecol. 2005 Feb. 105(2):325-32. [Medline].
Sjoborg KD, Vistad I, Myhr SS, Svenningsen R, Herzog C, Kloster-Jensen A, et al. G, Hole S, Tanbo T.: Pregnancy outcome after cervical cone excision: a case-control study. 2007;86(4):. Acta Obstet Gynecol Scand. 4/2007. 86:423-8.). [Medline].
Nordland K, Skjeldestad FE, Hagen B. [Treatment of cervical intraepithelial neoplasia before and after introduction of laser conization]. Tidsskr Nor Laegeforen. 2005 Jan 20. 125(2):167-9. [Medline].
Baggish MS. Basic and Advanced Laser Surgery in Gynecology. 2nd ed. Norwalk, Conn: Appleton & Lange; 1999.
Bosch FX, Manos MM, Munoz N, et al. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst. 1995 Jun 7. 87(11):796-802. [Medline].
Duncan LD, Jacob SV. Atypical squamous cells, cannot exclude a high-grade squamous intraepithelial lesion: the practice experience of a hospital-based reference laboratory with this new Bethesda system diagnostic category. Diagn Cytopathol. 2005 Apr. 32(4):243-6. [Medline].
Ferenczy A, Franco E, Arseneau J, et al. Diagnostic performance of Hybrid Capture human papillomavirus deoxyribonucleic acid assay combined with liquid-based cytologic study. Am J Obstet Gynecol. 1996 Sep. 175(3 Pt 1):651-6. [Medline].
Gilles C, Manigart Y, Konopnicki D, et al. Management and outcome of cervical intraepithelial neoplasia lesions: a study of matched cases according to HIV status. Gynecol Oncol. 2005 Jan. 96(1):112-8. [Medline].
Hatch KD, Schneider A, Abdel-Nour MW. An evaluation of human papillomavirus testing for intermediate- and high-risk types as triage before colposcopy. Am J Obstet Gynecol. 1995 Apr. 172(4 Pt 1):1150-5; discussion 1155-7. [Medline].
Jordan MJ, Bader GM, Day E. Carcinoma in situ of the cervix and related lesions. An 11-year prospective study. Am J Obstet Gynecol. 1964. 80:160-82.
Kurman RJ, Solomon D. The Bethesda System for reporting cervical/vaginal cytologic diagnoses. New York, NY: Springer-Verlag; 1994. 30-78.
Lachman MF, Cavallo-Calvanese C. Qualification of atypical squamous cells of undetermined significance in an independent laboratory: is it useful or significant?. Am J Obstet Gynecol. 1998 Aug. 179(2):421-9. [Medline].
Lonky NM, Sadeghi M, Tsadik GW, et al. The clinical significance of the poor correlation of cervical dysplasia and cervical malignancy with referral cytologic results. Am J Obstet Gynecol. 1999 Sep. 181(3):560-6. [Medline].
Lorincz AT, Reid R, Jenson AB, et al. Human papillomavirus infection of the cervix: relative risk associations of 15 common anogenital types. Obstet Gynecol. 1992 Mar. 79(3):328-37. [Medline].
National Cancer Institute. Estimated new cancer causes and deaths in 2005. SEER Cancer Statistics Review, 1975-2002. [Full Text].
Numnum TM, Kirby TO, Leath CA, et al. A prospective evaluation of “see and treat” in women with HSIL Pap smear results: is this an appropriate strategy?. J Low Genit Tract Dis. 2005 Jan. 9(1):2-6. [Medline].
Nyirjesy I. Atypical or suspicious cervical smears. An aggressive diagnostic approach. JAMA. 1972 Nov 6. 222(6):691-3. [Medline].
Nyirjesy I, Billingsley FS. Potential hazards of following atypical and low-grade cervical cytology without colposcopy. 1998 Jul 1. 5(4):162. [Medline].
Nyirjesy I, Billingsley FS, Forman MR. Evaluation of atypical and low-grade cervical cytology in private practice. Obstet Gynecol. 1998 Oct. 92(4 Pt 1):601-7. [Medline].
Penna C, Fambrini M, Fallani MG, et al. Laser CO2 conization in postmenopausal age: risk of cervical stenosis and unsatisfactory follow-up. Gynecol Oncol. 2005 Mar. 96(3):771-5. [Medline].
Solomon D, Schiffman M, Tarone R, et al. Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial. J Natl Cancer Inst. 2001 Feb 21. 93(4):293-9. [Medline].
Stoler MH, Schiffman M. Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage Study. JAMA. 2001 Mar 21. 285(11):1500-5. [Medline].
Temkin SM, Hellmann M, Lee YC, Abulafia O. Dysplastic endocervical curettings: a predictor of cervical squamous cell carcinoma. Am J Obstet Gynecol. 2007 May. 196(5):469.e1-4. [Medline].
[Guideline] World Health Organization. WHO Guidelines for Treatment of Cervical Intraepithelial Neoplasia 2–3 and Adenocarcinoma in situ: Cryotherapy, Large Loop Excision of the Transformation Zone, and Cold Knife Conization. 2014. [Medline]. [Full Text].
Istvan Nyirjesy, MD, FACOG Former Clinical Professor, Honorary Staff, Department of Obstetrics and Gynecology, Georgetown University School of Medicine; Former Private Practice in Obstetrics and Gynecology
Istvan Nyirjesy, MD, FACOG is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, Association of Professors of Gynecology and Obstetrics, International College of Surgeons, Royal Society of Medicine
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Warner K Huh, MD Professor, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Senior Scientist, Comprehensive Cancer Center, University of Alabama School of Medicine
Warner K Huh, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American College of Surgeons, Massachusetts Medical Society, Society of Gynecologic Oncology, American Society of Clinical Oncology
Disclosure: I have received consulting fees for: Merck; THEVAX.
Conization of Cervix
Research & References of Conization of Cervix|A&C Accounting And Tax Services