Carbon Dioxide Laser Surgery in Gynecology Treatment & Management

Anesthesia for CO₂ laser treatment of the cervix or external genitalia may be provided by local injection of lidocaine with or without epinephrine. ^{[36, 37]}  Prior to injecting local anesthetic, a topical preparation such as an anesthetic spray or gel may be applied to lessen pain from the injection. Use of local anesthetic with a vasoconstrictor solution (1% lidocaine with 1:100,000 epinephrine, 5-10 ml injected circumferentially around the cervical surface may be associated with less pain from the procedure and the vasoconstriction could lessen blood loss.

The surgical procedure may be accompanied by oral or injectable sedation, if desired by the physician or patient. When performed in a surgical suite with anesthesia personnel, additional intravenous, regional, or general anesthetic agents may be used.

Diagnostic laparoscopy with a 2-mm laparoscope may be an office procedure requiring only local anesthesia at incision sites. Moderate sedation protocols using oral or intravenous medications may supplement planned procedures. In office diagnostic laparoscopy may allow pain mapping to assist in formulating a management plan for pelvic pain. Documentation of disease presence and location may facilitate ongoing and future therapy

Treatment of endometriosis or adhesions in the pelvis using the CO₂ laser requires general anesthesia.

Positioning

For laser procedures of the cervix, the patient is placed in the dorsal lithotomy position, and a speculum of adequate size is used to fully visualize the cervix. A speculum with a dull surface that is specifically designed to prevent reflection of the laser beam should be used. A speculum of appropriate length and width should be chosen to prevent relaxation of the lateral vaginal walls that could limit cervical exposure and risk inadvertent laser damage.

Safety

For CO₂ laser of the external genitalia or cervix, the patient is draped in damp towels to absorb any misdirected laser beams, and the patient's eyes are protected with wet gauze or protective glasses. All personnel, except the physician operating the microscope, should also wear eye protection.

The cervix, vagina, or vulva is bathed in a 3% solution of acetic acid, and abnormalities are noted with the microscope before the laser is fired.

A smoke evacuator system is used to remove the vapor plume. This is accomplished most efficiently with (1) a suction catheter attached to the speculum with a conduit toward the cervix to maximize plume removal, or (2) a suction tip placed as far into the vagina as possible without interfering with the laser beam. Custom specula with smoke evacuation attachments are commercially available.

A small number of reports have noted that viral DNA sequences have been isolated from laser plume. Little information is known about the effects of this plume on operating room personnel. Contamination of objects in the operating room has also been noted. Animal studies have failed to demonstrate worrisome amounts of viral DNA or transmission of virus to animals. Assessment of laser plume for HPV transmission to humans is reassuring, though the number of studies is small. ^[38] Therefore, customary procedures for use of plume evacuation, including surgical masks, are currently the best practice. No present barrier technique will prevent all possible inspiration of debris or viral parts. The absence of documented infections in personnel is reassuring. Continued study of this situation is in progress. ^{[39, 40, 41]}

For intraoperative laser therapy, direct visualization of lesions consistent with endometriosis may be noted. Documentation of the findings are included in the operative dictation and with operative photography. Installation of sterile saline into the pelvis may assist visualization of some endometriotic lesions, particularly those with a cystic appearance.

Careful inspection of existing adhesions or endometriosis must not only include complete visualization of the lesions but careful visual evaluation of adjacent structures to minimize risk of injury with laser therapy. Irrigation fluid provides an excellent backstop to the laser beam and reduces injury to organs behind the site being treated. More recently CO2 laser therapies have been used in combined surgical procedures allowing ablations of disease at various depths and locations combined with resection of endometriosis involving the colon. ^{[22, 42]} The laser treatments can be delivered by robotic methods allowing precise delivery of therapy.  Intrapelvic use of the CO2 laser has also been used in laparoscopic myomectomy. ^[38]

Setting the laser

The desired power-density range for adequate ablation or excision of cervical lesions with minimal thermal damage to adjacent areas is 750-2000 W/cm² (generally, 20-30 W at a continuous setting), with an effective beam diameter of 1.5-2 mm to maximize ablation and hemostasis while minimizing lateral thermal damage. Super-pulse settings may also be used, and they are preferred by some to also reduce thermal damage. ^[43] The same laser settings may be used to coagulate an area being ablated or excised, but the overall power density delivered for coagulation may be reduced by enlarging the dot size or by reducing the watt setting on the laser, thus decreasing the watts used per cm². For treatment of the vagina or vulva/perianal area, 10 W is preferred to minimize scarring and lateral thermal damage.

For CO₂ laser procedures of the cervix, the entire transformation zone is identified and marked with an intermittent beam application, taking care to be at least 3-4 mm beyond the affected area of the cervix. If an adequate margin cannot be obtained, another type of treatment may be indicated. The entire circumference of the anticipated ablation area is outlined as if outlining a circle with dots. These dots are then connected, and the entire area is ablated with a consistent continuous movement of the laser beam. The area is measured periodically with a graduated probe used through the colposcope, and the ablation continues to a depth of 7-10 mm. Ablation to an additional depth of 2 mm may be performed at the endocervical margin to evert the endocervix and facilitate future evaluation of the transformation zone.

Any bleeding points encountered are treated with coagulation by increasing the dot size or decreasing the power setting. Additional ablation at the endocervix allows destruction of disease in gland crypts.

A lesion that is difficult to see may be observed in its entirety through the colposcope, through manipulation of the speculum, or with use of skin hooks to manipulate the cervix itself. A probe also may allow a change in angle to more completely visualize the endocervical opening. In addition, use of a vaginal sidewall retractor helps prevent redundant vaginal sidewalls from obscuring vision and helps avoid inadvertent thermal damage. All equipment used must be coated or treated to prevent reflection of stray laser beams.

For excisional procedures, the dots initially placed in a circumferential fashion are connected and the initial depth is taken to approximately 5 mm. Periodic measurements are performed using a graduated probe. Once a depth of 5 mm is reached, a skin-hook (with a dull surface) is used to pull the specimen medially from all directions while simultaneously firing the laser beam, thus creating a cone-shaped specimen. Once the endocervix is reached, many physicians make the final cut with a knife or scissors to allow the cephalad margin to be more easily evaluated by the pathologist and exclude thermal damage. Bleeding during the excisional procedure or after the specimen is removed from the site is controlled with the laser, by defocusing the beam (increasing the dot size), decreasing the wattage, or both.

For CO₂ laser procedures of the vagina, a Teflon-coated speculum with a built-in smoke evacuator is placed into the vagina and the entire area of interest is visualized, both with the operator's eye and then via the colposcope. Acetic acid application may assist visualization of condylomata, but Lugols solution may be preferable for visualization of dysplastic areas. Although these areas had been preoperatively visualized in the office, careful re-evaluation in the operating room should be made before using the laser. CO₂ laser therapy is ideally suited for management of multiple lesions with ablation procedures preferred over excisional procedures due to the thin layer of squamous epithelium of the vagina. Excision without careful control of depth may result in injury to the bladder or bowel. CO₂ laser of lesions may alternatively be used with a handheld device, but the colposcope provides more accurate depth control.

Lesions should be completely ablated and a 1-cm margin should be left on all sides of the lesions.

The laser is customarily set at 10 W via a super pulse or continuous setting. Laser depth is controlled by varying the spot size. Avoid pinpoint settings, which result in greater cutting and depth with less coagulation. Continuous movement of the beam also prevents inadvertent excess penetration. Coagulation of small vessels may be assisted with additional beam defocusing or reduced power settings. Excess laser use to control bleeding should be avoided. A suture may be required in some areas.

Altering the angle of speculum placement, turning the blades 90 degrees, using a lateral vaginal sidewall retractor, or even shooting the laser through the side of a bi-valve speculum may allow visualization and therapy of all affected areas. The procedure should be conducted from the vaginal apex outward to the introitus. Relaxing the 2 valves of the speculum allows the vaginal sidewalls to move toward each other and may also enhance visualization.

Individual condylomata are ablated and then the margins are treated. VAIN lesions are treated by the same principle of ablation of the individual lesions followed by creation of a 1-cm margin. Although a measuring tool or probe may be used with colposcopic visualization, the preferred depth of 2-3 mm within the vagina is generally easily noted with the operator's eyes and colposcope.

For CO₂ laser of the vulva, perineum, or perianal areas, a power setting of 10 W represents a good starting setting. Estrogen-deficient women (premenarchal or postmenopausal) may require decreased power density via increasing the spot size and decreasing the power settings. Children require no more than 2-5 W for laser therapy of condylomata. Higher power settings may result in excess depth and secondary scarring.

Preoperative application of 5% acetic acid improves lesion visualization. This may be applied using a damp gauze while final operative preparations are made and the patient is positioned. Damp towels should be placed around the areas for laser therapy and around the vaginal introitus for cervical, vaginal or vulvar ablations to minimize damage from stray laser beams.

Genital condylomata are ablated to the level of the skin surface and then to surgical plane 1 (see Table below). If fat is seen, the depth of ablation is too deep and destruction of skin structures or bleeding may result. Char should be removed via wiping with a damp gauze using sterile saline or acetic acid.

A hand-held laser device may be used on the vulva, but a colposcope may be preferable for accurate visualization of the individual lesions. An anoscope may assist visualization of both condylomatous or dysplastic lesions at the anal opening. Lesions of the urethral meatus may be treated by the colposcope; however, lesions within the urethra itself may require urologic consultation and urethroscopy.

On the vulva, perineum, or perianal areas, condylomatous and dysplastic lesions are initially treated with a 1-cm margin. Care should be taken not to exceed 2-3 mm of depth for dysplastic lesions and surgical plane 1 only for condylomatous lesions.

Table. The 4 Surgical Planes in Laser Surgery of the Vulva* (Open Table in a new window)

For intra-abdominal and intrapelvic applications of the CO₂ laser, lesions must be visualized and all anatomic landmarks identified. Ablation of lesions, lysis of adhesions, or excision of the peritoneum involving an endometriotic or adhesive lesion must be based on individual anatomic findings and operator experience. Failure to use thorough visualization of anatomic landmarks may result in injury to bowel, bladder, or vascular structures. Additional laser procedures, such as bilateral laser destruction of the medial portions of the uterosacral ligaments to decrease pelvic pain have been studied with variable results. Several lasers have been used for intra-abdominal applications. Operator experience may dictate the laser choice. Lasers with gynecologic applications include CO₂ laser, KTP laser, Argon laser, and Nd:YAG laser.

Preoperative medical therapy may also enhance visualization of endometriotic lesions and decrease the size of areas to be treated. Additional laparoscopic procedures considered for surgical intervention with laser therapy are as follows: ^[44]

• Ablation of endometriosis

• Lysis of adhesions

• Resection of endometriosis

• Ovarian cystectomy

• Salpingo-oophorectomy

• Partial salpingectomy

• Myomectomy

• Laparoscopically assisted vaginal hysterectomy

A subumbilical port is the customary place to locate the laser laparoscope. Smoke evacuation is via a secondary port, usually 5 mm in diameter. Adequate visualization of all areas to be treated may require multiple ports, customarily 5 mm. These should be placed by traditional laparoscopic procedure, under direct visualization and with consideration of local skin anesthesia injected before the entry of each port. Likewise, each site should be visualized when removing the trochar at the completion of the procedure. Installation of saline with or without heparin or other substances to decrease adhesions is controversial but warrants individual consideration. Rigorous hemostasis should be used, as this may reduce postoperative adhesion formation.

Preoperative antibiotic therapy is not recommended for intra-abdominal laser applications. Preoperative bowel prep is recommended to maximize safety and decrease complications in the event of a bowel injury. A sponge stick or uterine manipulator should be placed in the vagina or cervix, respectively, to assist movement of the uterus or vaginal apex to enhance visualization.

Intraoperative photography may enhance postoperative patient counseling. Trochar incision sites 10 mm or more require suture closure of the fascia, while those of smaller diameter may be closed with a stitch or skin glue. ^[24]

Pain management following laser procedures to the external genitalia, vagina, or cervix may consist of nonsteroidal anti-inflammatory agents (NSAIDS) and narcotics. Initial dosing should be given preoperatively with oral medications or intraoperatively with IV medications in the office setting and intravenous medications in the operative suite.

Pain management following intra-abdominal procedures may also be maximized with preoperative pain medications and antiemetics. Local anesthesia applied to incision sites decreases pain from trochar placement. Following laparoscopy, rapid progress to normal activity, regular diet, and normal bowel function should be expected or evaluated if absent. Worsening pain, increasing abdominal extension, nausea, or vomiting require prompt attention to exclude intra-abdominal damage of the bowel.

Pain management of vulva or perianal lesions may also be facilitated by topical lidocaine jelly (2%) or ointment (5%), silver sulfadiazine cream, ice packs, and sitz baths of warm water with or without Epsom salts.

Vaginal postoperative care of postmenopausal women not currently using systemic or topical hormone therapy, may include small amounts of estrogen cream, 0.5-1 g intravaginally at night to increase the rate of re-epithelialization of the vaginal tissue and decrease the risk of vaginal scars.

The frequency of postoperative cytologic testing should be correlated to the disease detected at the time of excisional procedures. Consensus guidelines for the management of abnormal cervical cancer screening and cancer precursors were updated in 2012 and published in 2013 in the Journal of Lower Genital Tract Disease. ^[24]

 

 

 

Postoperative patient instructions may vary from one provider to another and may also change in accordance with additional patient medical conditions. General postoperative instructions include (1) pelvic rest (ie, no tampons, douching, or intercourse) until the scheduled postoperative follow-up examination; (2) light activity for 3-5 days postoperatively, especially no heavy lifting or excessive strenuous activities; and (3) instructions to call if a foul vaginal discharge, pelvic pain, fever, or excess bleeding develops for 2-4 weeks.

Consensus guidelines developed in 2012 by the American Society for Colposcopy and Cervical Pathology (ASCCP) include the following ^[24] :

CIN grade 1

Cervical intraepithelial neoplasia (CIN) 1 lesions are heterogeneous; most are associated with the presence of high risk types of human papillomavirus (HPV). Others are heterogeneous with respect to markers of neoplasia. CIN 1 rarely progresses to CIN 2 or 3. The risk of having an undetected higher-grade lesion is greater if the biopsy diagnosis of CIN 1 was preceded by cytology showing high grade squamous intraepithelial lesions (HSIL); atypical squamous cells, cannot exclude HSIL (ASC-H); or atypical glandular cells (AGC).

Co-testing at 1 year is recommended; if both cytology and HPV tests are negative, then testing in 3 years is appropriate—using cytology if the patient is younger than 30 years or co-testing if older than 30 years. At that time, if testing is negative, the patient is returned to routine screening for her age. If any testing result is abnormal, then colposcopy is recommended.

When CIN 1 persists for at least 2 years, either continued follow-up or treatment is acceptable. If treatment is selected, then a colposcopy is performed and if adequate, an ablative or excisional procedure is acceptable. A diagnostic excisional procedure is needed if the colposcopy is inadequate, if the endocervical sampling reveals CIN 2 or higher (or ungraded CIN), or if the patient has been previously treated.

In women whose testing reveals CIN 1, or no lesion, preceded by HSIL or ASC-H, observation with co-testing at 12 and 24 months or management with a diagnostic excisional procedure may be undertaken. Observation may be chosen if the colposcopy finding is satisfactory and the endocervical sampling is negative for dysplasia. If the co-testing at 12 and 24 months is negative, then the patient is returned to routine screening for her age. If any tests are abnormal, then colposcopy should be performed. An excisional procedure should be performed if HSIL cytology is found at the 12- or 24-month visit.

For women age 21-24 years, cytology at 12-month intervals is performed; however, HPV testing is NOT recommended. For any cytology results reported as ASC-H or HSIL, colposcopy is recommended. Then, if CIN 1 is diagnosed, continued cytology and colposcopy at 6-month intervals is recommended. Biopsy is performed if a high-grade lesion or HSIL cytology is diagnosed. If the colposcopy study is inadequate, if CIN 2 or higher is found, or if CIN is identified in the endocervix sample, an excisional procedure is performed. Recommendations are similar for women younger than 21 years who have been screened inadvertently. For pregnant women with CIN 1, no treatment is recommended, but testing is repeated postpartum.

CIN grades 2 and 3

Although more than 40% of untreated CIN 2 lesions regress without interventional therapy, approximately one third will persist and 22% will progress to carcinoma in situ or invasive cervical disease. ^[45] The procedures for cervical ablation or excisional methods can be used to treat women with biopsy confirmed CIN 2, 3 and a satisfactory colposcopic examination. An excisional procedure with positive pathology at the margins followed by an unsatisfactory colposcopy is generally considered a risk factor for recurrent or persistent CIN.

At the time of a diagnostic procedure, endocervical sampling correlates with endocervical margin status. Positive evidence of disease at the endocervical margin is predictive of residual dysplasia in 10-33% of recent studies. ^[46] Women are recommended to be counseled about their increased risk for recurrent or persistent CIN when pathology results following treatment reveal positive margins. For those patients in whom further treatment is decided, an excisional procedure may be preferred with hysterectomy also a viable option for women who have completed child bearing.

After treatment for CIN 2 or 3, co-testing at 12 and 24 months is recommended. If both tests are negative, co-testing in 3 years is recommended. If all tests are negative, routine testing is recommended for at least 20 years. This testing should be continued even if it extends testing beyond age 65 years. If any abnormalities are identified, colposcopy with endocervical sampling is required.

When an endocervical curettage (ECC) sample is positive at the time of treatment, or margins are positive at the time of treatment, re-assessment with cytology and endocervical sampling should be performed. A repeat excisional procedure or hysterectomy (when repeat excision is not feasible) is acceptable.

Young women, aged 21- 24 years with CIN 2 or 3 histology may either be treated (as outlined above), or they may undergo observation. Observation for 12 months consists of cytology and adequate colposcopy at 6-month intervals. Repeat biopsy is indicated for worsening lesion appearance, evidence of a high-grade colposcopic finding, or HSIL cytology. Treatment is recommended for inadequate colposcopy, if CIN 2 or 3 persists for 24 months or if CIN 3 is diagnosed. Treatment guidelines are the same as those listed above for older women. During pregnancy, periodic cytology and observational colposcopy are sufficient for CIN 2 or 3—unless invasive disease is suspected. In the absence of findings suggesting invasive disease, postponing reevaluation until 6 weeks' or longer postpartum is acceptable.

Algorithms for the management of genital dysplasias are available from the American Society for Colposcopy and Cervical Cytology.

Adenocarcinoma in situ

The management of adenocarcinoma in situ is often difficult since this disease process frequently extends well into the endocervical canal and may be multifocal or possess "skip lesions." Invasion cannot be excluded without an excisional procedure, but negative margins performed after an excisional procedure do not guarantee the disease has been completely removed. In most patients, however, an excisional procedure is curative. The failure rate following an excisional procedure ranges from 0-9%. ^[47] Positive endocervical cytology at the time of an excisional procedure may also be indicative of residual disease, as is a positive margin in the excised specimen.

Hysterectomy is preferred as a management strategy in women who have completed childbearing and possessed the diagnosis of AIS at the time of an excisional procedure. Women who wish to maintain fertility may be observed. A negative HPV test at follow-up indicates a lower risk of persistent or recurrent disease. Reevaluation at 6 months with co-testing, colposcopy, and endocervical sampling should be performed. A reexcision is indicated if a positive endocervical sample or a positive margin is noted in the excised tissue excised Long-term follow-up is needed if hysterectomy is not performed.

 

Complications associated with ablative or excisional procedures performed using the carbon dioxide laser include bleeding, infection, cervical scarring or stenosis, altered fertility, anesthetic complications, premature labor, and cervical insufficiency.

Bleeding may occur at the time of the procedure or within 4-10 days postoperatively. Procedural blood loss may be minimized by scheduling the procedure during the follicular phase of the menstrual cycle.

Bleeding in the days following the procedure may stem from arterial recanalization. Inspection of the operative site should be performed at any point if the patient feels the amount of bleeding is worrisome. Topical treatments (eg, Monsel solution, silver nitrate) may be applied to any specific bleeding sites. Visualization of a clot in the surgical bed without evidence of active bleeding warrants observation only. Removing the clot often causes the bleeding to resume. The patient should be advised to call if persistent bleeding more than a heavy period occurs.

The rate of bleeding after laser procedures has been reported to be approximately 5%, which is similar to that following other excisional procedures of the cervix. ^[48]

Long-term complications following laser procedures of the uterine cervix include possible reduced ability to visualize the transformation zone. This can occur after any surgical procedure of the cervix.

Ablative or excisional laser procedures and recurrent or multiple procedures performed on the cervix are also associated with cervical stenosis and may be associated with a loss of endocervical glands due to lasering in the proximity of the internal os. This may be preventable by attempting to destroy a smaller volume of cervix (if feasible without compromising the treatment). In postmenopausal women, the incidence of stenosis may be reduced with the adjunctive administration of vaginal estrogen cream postoperatively. This may also reduce stenosis or foreshortening of the upper portion of the vagina following laser therapy for condylomata or dysplasia. ^[49]

Any surgical procedure on the uterine cervix, especially recurrent procedures or the destruction of a large volume of cervical tissue, is associated with a loss of cervical volume and may result in cervical insufficiency and secondary premature labor or pregnancy loss. ^{[50, 51]} However, fertility rates are not generally altered by a single procedure. Fertility rates may be reduced following multiple procedures, due to destruction of the endocervical glands and secondary reduction of endocervical mucous or cervical stenosis.

Postoperative repeat cytology following CO₂ laser therapy management of cervical dysplasia is dictated by the pathology noted on colposcopy-directed biopsies performed preoperatively or on the operative pathology of the excisional specimen of the transformation zone. Guidelines for follow-up may be obtained from the ASCCP recommendations.

Postoperative care following ablation of condylomata of the vulva, vagina, or cervix consist of evaluation for healing and follow-up based on patient symptoms or other gynecologic indications.

Laparoscopic management following adhesiolysis or endometriosis consists of observation. Continued medical therapy to prevent recurrence of endometriosis may be individualized.

Infection can occur after any ablative or excisional procedure on the cervix, vagina, or vulva. Normal healing following CO₂ laser procedures to the cervix or vagina is accompanied by a moderate, malodorous discharge associated with sloughing of dead cells. This discharge may be difficult to distinguish from infectious discharge and the altered chemical environment in the vagina may be associated with symptomatic bacterial vaginosis. Signs of true infection may include pelvic pain, fever, and other symptoms associated with endometritis or salpingitis. An infection may also be manifested by prolonged bleeding or delayed postoperative healing.

Postoperative bleeding from the cervix may be decreased by scheduling the procedure during the week following menses (ie, the follicular phase of the menstrual cycle). Careful visual inspection of the cervix and vagina, judicious testing for sexually transmitted infections, and wet mount examination of the vagina prior to surgery may allow preoperative eradication of potential agents associated with infection (eg, gonorrhea, chlamydia, bacterial vaginosis).

Anesthetic complications of office procedures include risks associated with local anesthesia and systemic absorption of the anesthetic agent. These include ringing in ears, dizziness, and rarely seizures and cardiac arrest. Care in these instances consists of systematic measures and if seizures or cardiac arrest occurs, transfer for hospitalization and evaluation. Office procedures should only be performed when staff and equipment are available to deal with any emergency, including items and persons for cardiopulmonary resuscitation and a crash cart. Patients with known pre-existing medical disorders (eg seizure disorder) should be considered for procedures in the surgical setting with anesthesia administered by a physician or nurse anesthetist.

Injuries to members of the operating team or to the patient may result from improper deployment of the laser or an accidental burn due to deflected laser beam. Appropriate draping with damp towels and eyewear by all members of the team, except the surgeon operating the microscope, is important.

Complications of the CO₂ laser procedures in the vagina include scarring and obliteration of the vaginal apex with secondary loss of length and configuration. Dyspareunia may result and foreshortening may limit adequate future evaluation.

Laser therapy of the vulva, perineum, or perirectal areas generally results in minimal scarring or loss of architecture, but excess depths of laser therapy increase the chance of alteration of anatomy due to scarring, dyspareunia, pain with defecation, or labial adhesions.

Intra-abdominal laser therapy may result in a failure to eradicate adhesions or endometriosis, new adhesion formation or dyspareunia. Intraoperative injury to bowel or bladder usually manifests itself in the early postoperative period and requires a high index of suspicion, prompt therapy, and possible surgical intervention with further therapy to injured organ.

Complications associated with any laparoscopic procedure are as follows:

• Injury to vessels or intra-abdominal structures

• Cardiorespiratory problems secondary to pneumoperitoneum

• Pneumothorax

• Decreased venous return

• Gas embolism

• Cardiac arrhythmias

• Abdominal wall hematomas

• Incisional infections

• Incisional hernias

Disease eradication and recurrence rates following carbon dioxide laser therapy compare favorably with other excisional or ablative procedures. Outcomes are compared with the assumption that similar preprocedural evaluations (eg, cervical cytology, colposcopy, biopsies) have been performed. ^[36]

Carbon dioxide laser procedures eradicate CIN in up to 90% of cases. ^[52] Likewise, eradication of VAIN or VIN is similar in comparison to other excisional or ablative procedures in these locations. However, because of the pathophysiology of HPV, an operative procedure results in a reduced viral load and excision of overtly diseased tissue, but does not completely eradicate the virus from the host. Complete eradication of the virus is a function of the patient's immune system.

A randomized trial of cryotherapy, carbon dioxide laser vaporization, and LEEP for CIN, showed relatively similar rates of disease persistence and recurrence with each of the modalities over follow-up periods of 6-37 months. Recurrences are more likely to occur in women (aged 30 years or older), women with HPV type 16, and women with prior dysplasia. Persistent disease was more common in women with larger lesions, a factor that in other studies has been shown to be better managed by carbon dioxide laser procedures than other modalities. ^[45] Many recurrences of cervical dysplasia are associated with prior positive ectocervical or endocervical margins. ^[48]

The 2012 Updated Consensus Guidelines for the Management of Abnormal Cervical Cancer Screening Tests and Cancer Precursors recommends that women with HIV or other immunosuppression be managed in the same fashion as immunocompetent women. ^[24]

In immunologically intact women, appropriate dysplasias treated with carbon dioxide laser procedures may result in complete eradication of the HPV genome. ^[53]

In a study by Kjellberg et al, cervical dysplasias ranging from mild to severe were evaluated with colposcopy and biopsy results, and the patients were treated with carbon dioxide laser conization. The presence of HPV in the removed specimen was documented by HPV testing and was positive in 73.2% of patients before excision. At follow-up, only 3 women were positive for HPV, but no women had the same HPV type at 2 follow-up visits over 22-46 months. Only 2 postoperative samples had squamous cell atypia. ^{[53, 54, 55, 56, 57, 58, 59, 60]}

Several investigators have found that the results of carbon dioxide laser procedures are similar to those of cold-knife conization procedures or LEEPs for the recurrence of neoplasia. Many recurrences are associated with positive ectocervical or endocervical margins at the prior procedure. ^[48]

Recurrence or persistence of endometriosis in pelvic organs may also be dependent on individual host factors and immune function. Both endometriosis and adhesions may result in altered pelvic anatomic relationships leading to dyspareunia, reduced fertility rates, and increased risk of ectopic pregnancy. Therapy following CO₂ laser treatment must be individualized based on patient presentation, clinical symptoms, and individual anatomic findings.

Extensive review of publications incorporated in the development of the 2012 Consensus Guidelines Conference and conference participants identified several areas important for the clinical care of women but which currently have insufficient evidence for definitive recommendations. ^[24]  Note the following:

1. More information is needed to determine post treatment outcomes and optimal long-term followup of women treated for CIN 2 and 3 managed with serial co-testing.
2. More evidence is needed before developing management guidelines for women with negative colposcopy evaluation, but with abnormal cytology or with CIN1. 
3. More followup studies of women whose management utilized HPV genotyping, immunostains or cytogenetics are needed to incorporate these new testing modalities into management guidelines.
4. Information about the long-term effects of HPV vaccinations on viral natural history and management of HPV related disease is currently not known.
5. Evidence of the safety of observation and fertility protection of young women with high grade histologic lesions and the rates of regression or progression of HPV disease of the cervix is not yet available.

As evidence in these areas emerges, management recommendations utilizing the CO₂ laser may also be modified. ^[61]

The utilization of the bivalent (human papillomavirus [HPV] types 16,18) or quadrivalent (HPV types 6,11,16,18) vaccines for HPV remain the best preventive strategy. ^[24] These vaccines provide clear benefit when administered to women and men ages 9-26 years, and they may be of benefit to other populations based on research in progress. Vaccines in development will include more HPV types.

The effects of vaccinations of large populations over the long term remain unknown. It is also unknown if vaccination alters the natural history of HPV disease or whether it should alter management strategies in cases of histologic abnormalities. Therefore, women who have received an HPV vaccine should undergo the current guidelines' recommended cytologic testing and treatment.