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.

Frequency

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, the American Cancer Society predicted 13,170 new cases of invasive cervical cancer and 4,250 deaths due to cervical cancer in 2019.[5] The average age at diagnosis is between ages 35 and 44 years; it is rarely diagnosed in woman younger than 20 years.

Worldwide, cervical cancer is the second leading cause of cancer death in women. 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.[6]

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

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

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.[7]

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%.[1] Bjerre et al reported treatment failure in 7% of their patients who received therapeutic conization.[2]

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.

Cytology

In the United States and in many other countries, cytologic findings are reported according to the Bethesda System. Epithelial cell anomalies are reported as follows:

• Atypical squamous cells of undetermined significance (ASCUS): The ASCUS category was modified in 2001. The category has been renamed atypical squamous cells (ASC) and is subdivided into the following groups: (1) atypical squamous cells of undetermined significance (ASC-US) and (2) atypical squamous cells cannot exclude HSIL (ASC-H).

• Atypical glandular cells of undetermined significance (AGUS): In 2001, this category was renamed atypical glandular cells. This category is further specified by cell type (endocervical, endometrial, or otherwise not specified). The subcategory favor neoplastic is maintained.

• LSIL or LGSIL - Encompasses HPV (ie, koilocytosis), mild dysplasia, and CIN grade 1 (CIN-1)

• HSIL or HGSIL - Encompasses moderate and severe dysplasia, carcinoma in situ, CIN grade 2 (CIN-2), and CIN grade 3 (CIN-3)

• Squamous cell carcinoma

• Endocervical adenocarcinoma

• Endometrial adenocarcinoma

• Extrauterine adenocarcinoma

• Adenocarcinoma, not otherwise specified

• Other malignant neoplasia

HSIL or LSIL cytology is the usual trigger to initiate colposcopy, diagnostic conization, or both. The presence of ASCUS or AGUS cytology, particularly when associated with high-risk HPV and no colposcopic anomaly, may also require the same approach (see Human Papillomavirus).

Cytologic categories must be carefully distinguished from histologic diagnoses. In general, cytology studies have a high sensitivity for CIN but a low specificity for determining its grade. Regrettably, cytologic and histologic diagnostic terms are often used interchangeably. Cytology results tend to lead to an underestimation of the severity of CIN. For example, high-grade (grades 2 and 3) CIN was preceded by HSIL in only 31% of cases in data compiled from 6 publications (see image below).

Testing for HPV

The presence of high-risk HPV (types 16,18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59), usually detected by performing the hybrid capture II test, reinforces the need for histologic diagnosis, even if cytology findings are reportedly normal or of undetermined significance.

Pathology

The most common pathologic terms used in histological diagnosis of cervical epithelial lesions are as follows:

• Cervical intraepithelial neoplasia, grade 1 - Mild dysplasia

• Cervical intraepithelial neoplasia, grade 2 - Moderate dysplasia

• Cervical intraepithelial neoplasia, grade 3 - Severe dysplasia, carcinoma in situ

• High-grade cervical intraepithelial neoplasia - CIN-2 or CIN-3 (carcinoma in situ = CIN-3)

• Microinvasive squamous cell carcinoma

• Squamous cell carcinoma

• Adenocarcinoma, endocervical

• Adenocarcinoma, endometrial

• Extrauterine adenocarcinoma

• Adenocarcinoma, not otherwise specified

• Other malignant neoplasia

Correlating preoperative and postoperative histologic diagnoses is indispensable to help determine the adequacy of the treatment and the type of follow-up care required.

A literature review estimates that errors of postconization pathologic diagnoses occur in 0.5-9% of the cases. Burghardt reported that errors increase significantly according to the number of sections made of the cone specimen and recommends the separate reading of 80-90 sections.[3]

In the United States, the intact cone specimen, ideally marked with a suture at the 12-o'clock position, is opened at this position, laid flat, and cut in 12 blocks in a radial manner. Each block is correlated to the hour of the clock and is separately embedded in paraffin. This routine permits the identification of the site of a positive margin. Determination of the original site of fragmented specimens is more difficult; therefore, removal of the specimen in one piece is recommended.

If pathology findings from the operative specimen do not correspond to those of the directed biopsies, more sections should be requested from the laboratory.

The only useful imaging study is colposcopic examination of the cervix. The meaning of changes visualized by colposcopy must be clarified by punch biopsy or conization.

Prior to selecting the method and extent of conization, consider the possibility of finding invasive cancer in the operative specimen. If the risk of invasion is high, such as in women with CIN-3, and colposcopy results have been less than satisfactory, consideration must be given to widening the margins both on the exocervix and in the cervical canal.

The desire for future childbearing must be discussed with each patient. In those who may desire future pregnancy, one must decide whether a shallow cone is adequate to accomplish the goal of conization because excision of the internal os could bring about cervical incompetence, resulting in late abortion or premature delivery.

The type of conization to be performed depends on the operator's training, on the available equipment, and on various circumstances discussed in Intraoperative details.

A randomized prospective trial by Mitchell et al found no statistically significant difference in outcomes among patients treated with cryotherapy, laser conization, or LEEP.[7] However, excisional methods yielded more tissue for histologic studies, while destructive procedures did not.

A thorough preoperative colposcopic evaluation with endocervical curettage, or at least endocervical cytology using an endocervical brush, should be performed prior to conization. Performing a Schiller test (painting the cervix with Lugol solution, which causes a deep brown stain of the healthy, glycogen-producing, squamous epithelium but leaves the dysplastic areas unstained) should allow correlation of the colposcopically visible exocervical margins with the iodine-negative areas. The presence of endocervical CIN indicates the need to excise more, perhaps even the entire cervical canal.

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[8] :

• 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).[8]

Cold-knife conization

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.[9]

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.

Laser conization

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).[10]

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[11] , 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.[12] 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.[13]

Wun et al reported that 11 of 248 patients (4.4%) had missed invasive carcinoma; close follow-up is therefore indispensable.[14]

From Denmark, Noehr et al reported preterm delivery in 43.4% of twin pregnancies that occurred following LEEP treatment.[15] Jacobson et al reported a preterm delivery in 6.5% before and 12% after the LEEP procedure.[16]

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.[17]

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.[18]

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.[19]

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.[20] 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.

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.

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.