Conization of Cervix Treatment & Management
- Author: Istvan Nyirjesy, MD, FACOG; Chief Editor: Warner K Huh, MD more...
Cold-knife conizations have decreased considerably in frequency following the wide acceptance of LEEP, which yields equivalent results, is more cost effective, and appears to cause less intraoperative and postoperative bleeding. However, the cold-knife approach may be preferable in situations in which evaluation of the margins is particularly critical or in situations in which the use of a diathermic loop is impossible because of the proximity of the exocervical margin to the vaginal fornix.
In some centers, the cold-knife approach is used exclusively if microinvasion or a glandular lesion is suggested. Cold-knife conization must be performed in a fully equipped operating room under general, epidural, or spinal anesthesia. Local anesthesia may be adequate in relaxed highly cooperative patients, but unexpected movements and vaginal tightness may interfere with an optimal conclusion.
Cold-knife conization can cause significant bleeding. Consequently, performing a preconization cerclage, as described in Cold-knife conization, or injecting the cervix with a vasoconstricting solution such as dilute vasopressin, phenylephrine, or epinephrine is advised. The vasopressin solution is prepared by adding 10 units of Pitressin to 30 mL of sterile water for injection. A maximum of 10 mL of this solution is injected in 1-mL increments into the cervical stroma around the transformation zone. Phenylephrine (Neo-Synephrine) is used in a concentration of 1:200,000. Epinephrine typically is used in combination with lidocaine in a 1:100,000 dilution (Xylocaine 1% with epinephrine). The author prefers to perform preconization cerclage in most cases because, in contrast to vasoconstrictor injections, this technique does not induce tachycardia or sudden blood pressure changes and tends to reduce delayed hemorrhage.
Some evidence indicates that conization performed during the first, rather than the second, half of the menstrual cycle is less likely to be associated with significant blood loss.
In 2014, the World Health Organization (WHO) released guidelines for the treatment of CIN with cryotherapy, LEEP, and cold-knife conization. These included the following recommendations for women with histologically confirmed CIN2 or CIN3, regardless of their human immunodeficiency virus (HIV) infection status :
The use of either cryotherapy, LEEP, or cold-knife conization is preferable to providing no treatment (strong recommendation)
Cryotherapy or LEEP should be used in women in whom either of these techniques would be appropriate, with no clear evidence suggesting that one technique should be preferred over the other (conditional recommendation)
The use of cryotherapy should be preferred over cold-knife conization in women in whom either of these techniques would be appropriate (strong recommendation)
The use of LEEP should be preferred over cold-knife conization in women in whom either of these techniques would be appropriate (strong recommendation)
In women with histologically confirmed adenocarcinoma in situ, according to the guidelines, the use of cold-knife conization should be preferred over LEEP, regardless of patient HIV status (conditional recommendation).
Under adequate anesthesia, the patient is placed in a dorsal lithotomy position and prepared and draped in the usual manner. A weighted speculum is inserted into the vagina.
For preconization cerclage (recommended to create a bloodless operative field, not as a prevention for cervical incompetence), 1-0 chromic catgut sutures with attached general closure needles are inserted at the 3- and 9-o'clock positions close to the vaginal fornix (see image below).
Cutting needles can also be used, but, in the author's experience, they tend to cause more bleeding. The needle attached to the 3-o'clock suture is used to perform the anterior portion of the cerclage by imbricating the suture in the anterior lip and by tying it to the needle-free end of the suture already anchored at the 9-o'clock position. The needle-ended suture at the 9-o'clock suture is used to complete the cerclage posteriorly. Inserting a black silk suture in the cervix at the 12-o'clock position is useful to help the pathologist orient the specimen.
For conization, sound the cervical canal to determine its length and the position of the internal os. Paint the cervix with Lugol solution and apply lateral traction to the angle sutures. Conization is performed with a No. 11 blade, which should be pointed toward the planned apex of the cone. The preferred approach is to start the incision at the 3- or 9-o'clock position and to cut posteriorly first to avoid loss of visualization from bleeding. The exocervical incision should include the entire transformation zone, with a 2- to 3-mm margin. If deep endocervical extension of the lesion into the endocervical canal is not present, the apex of the cone should end approximately 1 cm caudal to the internal os. Deep extension may necessitate excision of the internal os. Remove the cone specimen in one piece, if possible.
Following completion of the conization, the endocervical canal is curetted with a Kevorkian endocervical curette to help exclude the presence of residual lesions. Because of the cerclage, blood loss is usually minimal. To reduce oozing, Monsel solution (ferric subsulfate, a long-acting astringent, Mallinckrodt Chemical, St. Louis, Mo) may be used.
Historically, conizations were completed using a Sturmdorf procedure, which covers the raw stump with an anterior and posterior exocervical flap. This procedure is thought to be unnecessary by most surgeons, and concerns exist that hiding the coned area may cover deep-seated residual lesions. Sturmdorf procedures have not been shown to reduce the risk of delayed bleeding.
Some operators insert a small rubber drain in the cervical canal to reduce the risk of cervical stenosis. The value of this procedure is uncertain, and the author has not used it in recent years.
One should observe the operative site for a few minutes following the procedure to look for excessive bleeding. Arterial bleeding, uncommon if the cerclage approach is used, can be controlled by coagulation or by inserting U or figure-8 sutures. General oozing, if significant, is best treated by painting the stump with Monsel solution and/or by inserting a tight vaginal soft gauze pack (eg, Curlex), preceded by a sulfonamide or sterile lubricating cream. The patient may remove the packing 12-24 hours following insertion. Leaving a 5-cm protrusion of the packing beyond the introitus eases removal.
While laser conization is effective for treating CIN, it offers few advantages over LEEP or cold-knife approaches. Potential disadvantages include costly equipment and a possible coagulative effect on the margins, which makes histologic evaluation difficult. Gynecologists performing any type of laser surgery should attend specific courses on laser physics, safety features, and operative techniques. The author confines the use of lasers to patients with definitive diagnosis of CIN-2 or CIN-3 in whom a large lesion is close to the vaginal fornix or extends into the vault.
The operation is performed with carbon dioxide laser, using a colposcopic micromanipulator. While local anesthesia is used in some settings, the author recommends general anesthesia to reduce the chance of laser injury due to unexpected motion. A preconization cerclage can be performed as described in Cold-knife conization, or one can inject a vasoconstricting agent. A smoke/vapor evacuator is indispensable.
The procedure is begun by outlining the exocervical margins with 0.5- to 1-mm dots produced by laser energy at a power setting of 20-50 W. A laser incision is then performed to connect the dots and extended to a depth of 3-5 mm (see image below).
Laser, scalpel, or Mayo scissors may be used to complete the procedure. If laser is used for the conclusion, the stromal edge of the incision must be grasped and lifted with a hook to permit penetration of the laser beam towards the apex. Bleeders in the raw stump can be coagulated with defocused 2-mm laser dots or with a diathermic coagulator. The author has found that switching to cold-knife techniques following the initial annular incision with the laser reduces the time required for completion.
One variety of laser conization is called vaporization conization. It involves vaporization to a depth of 7 mm of the entire transformation zone, including a 2- to 3-mm margin. To accomplish this procedure, a spot size of 2 mm and a power setting of 25 W are commonly used. A gauge must be used to determine the precise depth of the vaporized area. Dorsey recommends dividing the area to be vaporized into 4 quadrants and completing the procedure by vaporizing an additional 2-3 mm of the endocervical canal.
Because vaporization conization does not provide a specimen for histologic evaluation, it should only be used in cases in which the entire lesion is visible colposcopically and does not extend into the endocervical canal. Pretreatment histologic diagnosis based on directed biopsies is mandatory.
Loop electrosurgical excision procedure
LEEP (LLETZ) procedures use diathermy current for excising all or selected areas of the transformation zone. The thin wire loop electrodes (see image below) are insulated to prevent thermocoagulative artifacts; consequently, the excised tissues are preserved for histologic examination. The author prefers to use pure cutting rather than blended current because the cutting current causes fewer thermal artifacts in the excised specimen.
LEEP is a precise and inexpensive technique that results in less bleeding than cold-knife or laser conizations. The author believes that it has proven itself as the best approach to conization in the overwhelming majority of patients. In rare patients with CIN, the size of the transformation zone exceeds the size of the largest loop. In such cases and in patients with vaginal fornix involvement, laser conization may be a better approach. The equipment for the LEEP procedure consists of a generator that creates high-frequency (350-1200 kHz) low-voltage (200-500 V) electric current. The generator is connected to an insulated thin wire loop, which is available in various sizes.
Most loop electrosurgical procedures can be performed under local anesthesia in an outpatient setting. The patient is placed in a lithotomy position and is attached to a grounding pad. An insulated speculum, connected to smoke-evacuator tubing, is used to prevent electric shock, which can occur if a noninsulated metal speculum is touched inadvertently by an active loop. For local anesthesia, the author injects 2-5 mL of lidocaine with epinephrine at the 3-, 6-, 9-, and 12-o'clock positions 1-2 mm beneath the surface of the cervical epithelium using a 25-gauge spinal needle. The use of epinephrine (or dilute vasopressin) is crucial to prevent intraoperative bleeding that could obscure the field of vision. If a patient is unable to relax, a safer plan may be to perform the procedure under general anesthesia because accidental burns of the vaginal wall can occur in patients who move during the procedure.
The loop size, usually 1.5-2 cm in width and 0.8-1.0 cm in depth, should be appropriate to remove the entire transformation zone with a 3-mm margin in one pass (see image below).
In the first pass, tissue is ablated to a depth of approximately 1 cm. Using a 1-cm by 1-cm loop, more of the endocervical canal can be excised in a second pass from the crater base. Once the cervix is adequately exposed, LEEP procedures can be performed with extreme rapidity, usually in less than 1 minute. The loop can be directed in a transverse direction (eg, from the 9- to 3-o'clock position) or anteroposteriorly (see image below).
Following the loop excision, the surface of the cervix appears raw. Painting it with Monsel solution can usually control oozing. Larger bleeders should be cauterized with a ball cautery tool.
Loop electrosurgical excision in "see-and-treat" settings
Conization procedures are usually performed after finding HSIL or LSIL after cytologic examination and confirming the presence of CIN-2 or CIN-3 by colposcopically directed cervical biopsy. While this classic approach is reliable, it necessitates 3 or 4 encounters and thus carries the risk of losing patients who do not return for follow-up.
The see-and-treat approach bypasses the colposcopically directed cervical biopsy; the indication for LEEP, performed during the first or second encounter, is based solely on the cytology report. This approach has the advantage of guaranteeing treatment of most high-grade CINs. The only disadvantage is the possibility of performing a LEEP in those in whom colposcopy would have excluded lesions that necessitate therapy and those who could have opted for follow-up observation. Considering the high level of safety associated with the LEEP, the benefit of prompt treatment of CIN most likely outweighs the risk in women in whom the indication is ambiguous. The universal application of the see-and-treat approach is currently not accepted; however, this approach is most valuable when follow-up evaluations of women are unsuccessful, such as in the lowest socioeconomic groups in both the United States and in developing countries.
Following any method of conization, complete healing of the cervix takes as long as 6 weeks. Intercourse and/or the use of vaginal tampons during the early healing period may cause significant bleeding and infections, and these activities should be restricted for at least 2-3 weeks.
Conization sites usually heal in 6 weeks. Reexamination of patients 2 weeks postoperatively is useful to help determine whether restrictions, such as coitus, can be lifted. A final postoperative examination is recommended at 6 weeks. To ascertain the absence of residual or recurrent CIN, Papanicolaou tests should be performed every 3 months during the first postoperative year and every 6 months thereafter. A single follow-up Papanicolaou test shows positive results in fewer than 25% of women with residual disease. Multiple studies report that any of the conization techniques cure at least 95% of patients who have CIN. Recurrence or persistence is significantly more common; 16.5% versus 1.9% according to Felix et al , in patients who had a positive margin for CIN in the postoperative specimen.
A 2007 study by Costa et al suggested that adding repeat HPV tests in conjunction with cytology offers clear advantages over a single cytology in monitoring women who were treated conservatively for cervical intraepithelial neoplasia.  Residual CIN III, ectocervical or endocervical margins positive for CIN, and/or positive endocervical curettings on cold-knife conization subsequent to LEEP all indicate a higher likelihood of harboring or developing cervical carcinoma.
In another study, Bae JH et al investigated the meaning of postconization persistence of HPV. The only significant risk factor for redevelopment of CIN after conization was the persistence of the same HPV subtype ( P < 0.0001) that induced the initial disease. 
Wun et al reported that 11 of 248 patients (4.4%) had missed invasive carcinoma; close follow-up is therefore indispensable. 
Roberta et al reported that the inclusion of mRNA testing at follow-up would enable the earlier prediction of the risk of residual/recurrent abnormalities. 
Intraoperative and postoperative bleeding are the most common complications of cervical conization. Both of these can be eliminated or significantly reduced if the above-described cerclage technique is practiced (see Cold-knife conization). Intracervical injection of dilute epinephrine or vasopressin into the cervix, contraindicated in patients with hypertension and those with cardiac problems, reduces intraoperative bleeding but not delayed bleeding, which usually occurs 7-14 days postoperatively in approximately 2% of the patients who undergo cold-knife conization.
Delayed bleeding, uncommon after LEEP, may be managed successfully in most women with the use of vaginal packing. Failure to respond to packing necessitates resuturing of the operative area.
According to a Canadian study, women who had a LEEP were more likely to deliver preterm (7.9% vs 2.5%) and to deliver preterm after premature rupture of membranes (3.5% vs 0.9%). Deliveries earlier than 34 weeks were not increased in the LEEP group. The mean birth weight was 3,432 g in the LEEP group and 3,495 g in the comparison group. No significant increase of severe neonatal morbidity and mortality was present.
A recent Scandinavian study also reported increased risk of preterm delivery, low birth weight, and premature rupture of membranes in subsequent pregnancies in women who were treated by laser coagulation or LEEP.
Other authors reported similar problems. Women of childbearing age should be made aware of such potential complications; however, lack of treatment of CIN-3 is probably more hazardous than premature delivery after 34 weeks. Cervical stenosis may occur in a few women. Inserting a rubber drain following the procedure has a limited role in the prevention of this often negligible complication. Cervical incompetence can result if the apex of the cone involves the internal os. Women who become pregnant after conization should be closely monitored for this potential complication, which is treated with cerclage.
In one study, a 98% cure rate with both laser conization (n=439) and cold-knife conization (n=212) was reported. Complications (eg, postoperative bleeding, infections, cervical stenosis) were significantly more frequent in the cold-knife group. Several reports suggest that involved margins and persistence of high-risk HPV are associated with increased risk of persistence and recurrence of CIN.
Both laser conization and LEEP generate smoke. Inhalation of smoke may be dangerous for the operator because the smoke may contain HPV particles. Therefore, the use of smoke evacuators is indispensable, and wearing a mask during the procedure is recommended.
Outcome and Prognosis
Most reports indicate that conization cures CIN in more than 90% of cases. However, these excellent results are not universal, and cure rates as low as 60% have also been reported. The reasons for treatment failure are unknown in most cases; positive margins are implicated in some studies. Because of the possibility of residual or recurrent disease, close follow-up observation is mandatory for all patients.
Future and Controversies
In the 1930s, more American women died of cervical cancer than breast cancer. Since the universal adoption of effective screening programs that lead to the diagnosis and treatment of high-grade intraepithelial neoplasias, invasive cervical carcinoma has become a relative rarity.
Despite these successes, controversies remain. Knowledge of the natural history of cervical cancer precursors is still incomplete. The medical community now realizes that the presumed continuum from CIN-1 to CIN-3 to invasive cancer is absent in the majority of cases. No tests can help indicate which case of CIN-1 will progress and which will regress. What is known is that leaving CIN-3 untreated leads to invasive cancer and death.
Based mainly on economic considerations, some groups recommend reduction of screening frequency and intermittent cytologic follow-up only for women with ASCUS or LSIL. The cost-effectiveness of performing colposcopy on all women with ASCUS or LSIL cytology is being questioned. The author considers cytology a risk indicator rather than a diagnostic test and believes that physicians have an obligation to their patients to reach an accurate diagnosis.
Recent data on the usefulness of testing for high-risk HPV-DNA raise hope that performing this testing may reduce the need for directed biopsies and diagnostic conizations. Despite the existence of major disagreements among observers regarding the interpretation of cytologic and histologic specimens, cytology, in combination with HPV-DNA tests and histology for the diagnosis and grading of CIN, is expected to remain the cornerstone of screening protocols for years to come. The ultimate decision on evaluating and treating is still in the hands of the clinical gynecologists. The author believes that physicians can better serve their patients by diagnosing and treating any cytologic change associated with a reasonable probability of CIN-3. Colposcopically directed biopsies and LEEP conizations resolve most of these issues with rare complications and at a relatively low cost. Hopefully, however, better understanding of the natural history and pathogenesis of CIN will yield even less traumatic approaches sometime in the future.
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].