You are in: eMedicine Specialties > Obstetrics and Gynecology > Gynecologic Surgery Carbon Dioxide Laser Surgery for Cervical DysplasiaArticle Last Updated: Dec 5, 2007AUTHOR AND EDITOR INFORMATIONAuthor: Janice L Bacon, MD, Professor and Chair, Department of Obstetrics and Gynecology, University of South Carolina School of Medicine Janice L Bacon is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association, Association of Professors of Gynecology and Obstetrics, Association of Reproductive Health Professionals, North American Society for Pediatric and Adolescent Gynecology, and South Carolina Medical Association Editors: Karen Loeb Lifford, MD, Director of General Gynecology, Associate Program Director, Department of Obstetrics and Gynecology, Instructor, Brigham and Women's Hospital, Harvard Medical School; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Frederick B Gaupp, MD, Consulting Staff, Department of Family Practice, Hancock Medical Center; David Chelmow, MD, Professor of Obstetrics and Gynecology, Tufts University School of Medicine; Program Director, Tufts University Affiliated Hospitals OB/GYN Residency Program; Chair, Tufts University Health Sciences Campus Institutional Review Board Author and Editor Disclosure Synonyms and related keywords: CO2 laser surgery, laser surgery, cervical intraepithelial neoplasia, CIN, human papilloma virus, HPV, squamous cervical abnormality, squamous carcinoma, squamous cell cancer, squamous intraepithelial lesion, SIL, cervical neoplasia, cervical cancer, cervical malignancy, atypical squamous cells of undetermined significance, ASCUS, cervical atypia, squamous atypias INTRODUCTIONHistory of the ProcedureThe key mechanisms of action of the laser were first discovered by Albert Einstein in the early 1900s. Initial results from the use of a carbon dioxide laser for the management of cervical dysplasia were less successful than anticipated initially because of an inability to determine penetration to an appropriate depth for reduction of recurrent disease. Not until 1978 did Anderson and Hartley emphasize the actual mechanics for the depth of cervical involvement.1 This task was further refined and shown to be both practical and efficacious by Jordan in 19852 and by Dorsey in 19793, when the Greater Baltimore Medical Center published the first clinical experience with cervical conizations by carbon dioxide laser. The carbon dioxide laser has been considered an effective modality for multiple tasks related to the treatment of cervical intraepithelial neoplasia (CIN), but most commonly for large lesions and for multifocal manifestations of human papilloma virus (HPV) disease. The use of this technology is limited in some areas because of healthcare provider and physician training experience and because of a lack of availability of equipment. Many hospitals require that specific credentials be obtained before using this modality, including documentation of didactic instruction and clinical supervision of initial procedures. ProblemThe US National Breast Cancer and Cervical Cancer Early Detection Program reports an overall rate of abnormal Papanicolaou test results of 3.8%, with specific rates for low-grade squamous lesions, high-grade squamous lesions, and squamous carcinoma of 2.9%, 0.8%, and 0.1%, respectively.4 In 2005, The US Centers for Disease Control and Prevention estimated that 20 million Americans are DNA positive for an anogenital type of HPV at any time. Almost half are sexually active adolescents or young adults aged 15-24 years. In the United States, 6.2 million individuals are estimated to become newly infected with HPV yearly. The specific cytologic terminology has been revised since Dr. Papanicolaou's original classification in 1954. It has evolved from the descriptive terminology of 1968, to the terminology cited above as CIN in 1978, and finally culminating with the Bethesda System classification initially released in 1988 and revised in 2001. Those cytologic abnormalities most amenable to carbon dioxide laser therapy are now categorized as squamous intraepithelial lesions (SILs). In addition to these cytologic abnormalities of the cervix (ie, SILs), the treatment of squamous abnormalities and condyloma of the vagina and vulva are possible using the laser. Before performing an ablative or excisional procedure, cytologic abnormalities are evaluated by biopsy. Optimal therapy for these problems is not confined to a single treatment algorithm, and several alternatives exist. Patient care must be individualized, and consideration must be given to age, parity, prior cervical cytologic abnormalities and treatments, plans for future childbearing, and the coexistent medical conditions of each patient. Carbon dioxide laser assists with conservative management of these cervical abnormalities. FrequencyHPV infection has been demonstrated to be a highly significant risk determinant of cervical neoplasia. High-risk HPV types (ie, 16, 18, 31, 45) exhibit the strongest association with cervical malignancy. The presence of the virus alone may not be the sole cause of SILs or malignancy. Additional factors of importance include the following:
Most women encounter HPV during their lifetime, and the cumulative prevalence rate is 25-60%.5 HPV infection may be present in women with normal cervical cytology, and most HPV types can cause mild or low-grade cervical cytologic abnormalities.6 As cytologic abnormalities become more severe (eg, high-grade SILs, moderate-to-severe dysplasia), a greater proportion of high-risk HPV types are identified.7 Terminology from the Bethesda System of cytologic evaluation of cervical cytology uses the term low-grade squamous intraepithelial lesion (LSIL) to refer to the cytological changes previously referred to as mild dysplasia, CIN 1, HPV effects, and koilo cytosis. In addition, the increased use of liquid-based cytology screening combined with this change in terminology has resulted in an increased number of Pap smears interpreted as LSIL. The median percentile reporting rate of LSIL in the United States was 2.4% for liquid-based specimens. EtiologyThe most likely etiology of squamous abnormalities of the cervix is infection with HPV, a double-stranded DNA tumor virus of the Papovaviridae family. The HPV has more than 100 subtypes and is present in more than 90% of preinvasive and invasive squamous neoplasms of the cervix. Serotypes associated with cervical squamous lesions may be designated as having a high or low risk for progression to malignancy. Ultimate cure of the viral infection can only be achieved by the immune system of the human host because papillomaviruses are ubiquitous in higher vertebrates. Approximately 25 types of HPV infect the genital tract. Higher risk types, including types 16 and 18, are classified as such because of the gene products that bind to tumor suppressor portions of the host cells and cause their ultimate inactivation. Interactions of HPV with histocompatibility antigens may help explain why the same HPV type leads to invasive disease in one patient and not in another. Treatment modalities, such as the carbon dioxide laser, destroy or excise infected cells, thus reducing the amount of infected tissue and, presumably, the host viral load. The subsequent healing process of the host stimulates viral combat at the surgical site. INDICATIONSPatients with abnormal cervical cytology findings must first be evaluated using colposcopy to help determine the location, extent, and severity of the clinical abnormalities. Colposcopically directed biopsies are indicated when, in the clinical opinion of the health care provider, CIN is present. Findings from one or more biopsy samples from the involved areas and findings from an endocervical curettage help document the location and histologic severity of the disease present. The carbon dioxide laser has been used for ablating CIN or excising abnormal areas, including the transformation zone. The carbon dioxide laser is customarily chosen over other ablative or excisional techniques when great precision is needed, particularly in situations involving large areas or when precise control over the depth of penetration is desired. Examples of procedures for which carbon dioxide laser is indicated include (1) ablation or excision of CIN in situations in which minimization of tissue destruction or removal is desired; (2) cervical treatment combined with treatment of dysplasia or condylomata or CIN on the vulvar, vaginal, perineal, or perirectal areas; and (3) multifocal cervical disease. The carbon dioxide laser is used in conjunction with a microscope or colposcope. This allows precise application, which is one advantage of this treatment modality. Another advantage of the laser is hemostasis and minimal thermal necrosis (<100 µm) when properly set. In addition, the procedure time is brief, and the laser may be used in an office or outpatient setting with the patient under local anesthesia. The office setting also may be more economical than procedures performed in an outpatient setting. RELEVANT ANATOMYHPV infects squamous and glandular cells of the cervix and squamous cells of the vagina and vulva. Evaluation of the cervix to detect abnormalities involves inspecting the cervix from the vaginal junction to the most cephalad extent of the visible endocervix. This, by definition, includes the transformation zone, the site where squamous and glandular cells meet and squamous metaplasia occurs. This area has the highest cell turnover and is by far the most common site for cytologic abnormalities. The transformation zone is the histopathologic term used to describe the area of squamous metaplasia. This area is located between the mature columnar cells of the endocervix and the mature squamous cells of the external cervical portio. Although a sharp edge of demarcation is seen in many patients, in others, this transformation zone is an area of more gradual cellular change. The term metaplasia is defined as the transformation of one mature cell type to another. The location of the transformation zone is customarily on the external cervical surface or within the endocervical canal, and its position is determined by a number of factors, including inflammation, vaginal pH, or the presence of exogenous or endogenous hormones (eg, estrogen). CONTRAINDICATIONSContraindications to using the carbon dioxide laser for the treatment of CIN include (1) an inability to visualize the area to be treated because of anatomic considerations (eg, prolapsing lateral vaginal sidewall), (2) preoperative histology findings indicative of malignancy, and (3) inadequate physician training or experience. Laser ablation is contraindicated if the entire lesion is not visible, although excision procedures may be performed. WORKUPLab Studies
Other TestsHPV typing is often discussed as a possible adjunctive test in the evaluation of cervical cytologic abnormalities. The 2006 ASCCP Consensus Guidelines recommend use of high-risk HPV testing in the evaluation of women with the following findings:
In 2003, the FDA approved the use of HPV typing as an adjunct to cervical cytologic screening in women aged 30 years or older. It may enhance the sensitivity to cytologic screening. Only high-risk HPV typing is useful in the management of cytologic abnormalities. HPV typing should not be used for screening in women younger than age 30. Diagnostic Procedures
TREATMENTSurgical therapyAnesthesia is provided by local injection of lidocaine with or without epinephrine. It may be accompanied by sedation, if desired by the physician or patient. When performed in a surgical suite with anesthesia personnel, additional intravenous, regional, or general agents may be used. Preoperative detailsPositioning The patient is placed in a dorsal lithotomy position, and a speculum of adequate size is used to fully visualize the cervix. Use a speculum with a dull surface that is specifically designed to reduce indirect reflection of the laser beam. Take care to choose a speculum of appropriate length and width to prevent relaxation of the lateral vaginal walls, limiting cervical exposure and risking inadvertent laser damage. The patient is draped in damp towels to absorb any misdirected laser beams, and the patient's eyes are protected appropriately in wet gauze or protective glasses. All personnel, except the physician operating the microscope, should also wear eye protection. The cervix is bathed in a 3% solution of acetic acid, and the cervical abnormalities are noted again 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. Setting the laser The desired power-density range for adequate ablation or excision 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 also may be used, and they are preferred by some to also reduce thermal damage.10 The same laser settings may be used to coagulate the portions of the cervix 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. Intraoperative detailsThe 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, 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. Any bleeding points encountered are treated with coagulation by increasing the dot size or decreasing the power. 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 the use of skin hooks to manipulate the cervix. A probe also may allow a change in angle to more completely visualize the endocervical opening. In addition, using 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 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. 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. Postoperative detailsThe frequency of postoperative cytologic testing should be correlated to the disease detected at the time of excisional procedures. The American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin recommends the following:11
Follow-upPostoperative patient instructions may vary from one provider to another and may also allow changes in accordance with additional patient medical conditions. General postoperative instructions frequently 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. COMPLICATIONSComplications 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 incompetent cervix. Bleeding may occur at the time of the procedure or 4-10 days after the procedure. 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 represents 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 occurs (usually described as heavier than a period). The rate of bleeding after laser procedures has been reported to be similar to that following a LEEP but less than that following a cold-knife conization procedure.15 The risk of bleeding following an uncomplicated laser ablation of the transformation zone, including all risks of bleeding (ie, acute, immediate, and following the procedure), is approximately 5% overall. 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. A preventive technique called buttoning may be performed at the time of the procedure and has been helpful in attempting to maintain visualization of the transformation zone. This involves vaporizing the cervical stroma 1-2 mm immediately surrounding the endocervical os. This assists with the eversion of the endometrial mucosa when healing occurs.16 Ablative or excisional laser procedures and recurrent or multiple procedures are also associated with cervical stenosis and may be associated with a loss of endocervical glands due to lasering close to the proximity of the internal os. This may be preventable by attempting smaller volumes of cervical destruction (if feasible without compromising the anticipated disease associated with the case). In postmenopausal women, the incidence of stenosis may be reduced with the adjunctive administration of vaginal estrogen cream postoperatively (Penna, 2005). 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 an incompetent cervix or premature labor.17, 18 However, fertility rates are not generally altered by a single procedure. Rates may be reduced following multiple procedures. This would occur because of destruction of the endocervical glands, resulting in decreased numbers of endocervical glands and leading to a reduced amount of endocervical mucus or to secondary cervical stenosis. Anesthetic complications include risks associated with local anesthesia and systemic absorption of the anesthetic agent. These include tingling in the ears, dizziness, and, rarely, seizures and cardiac arrest. Care in these instances consists of symptomatic 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 preexisting medical disorders (eg, seizure disorder) should be considered for procedures in a surgical suite with anesthesia administered by a physician or nurse anesthetist. Infection can occur after any ablative or excisional procedure on the cervix. Normal healing following carbon dioxide laser procedures is accompanied by a moderate, malodorous cervical discharge associated with sloughing of dead cells. This also occurs following LEEPs or cryotherapy. This discharge may be difficult to distinguish from infectious discharge, but signs of true infection include pelvic pain, fever, and symptoms of salpingitis. The presence of cervical infection may also manifest as prolonged bleeding or delayed healing postoperatively. Bleeding can be decreased by scheduling the procedure during the week following menses (ie, the follicular phase). Careful visual inspection of the cervix and vagina, judicious testing for sexually transmitted disease, and a wet mount examination of the vagina prior to surgery may allow preoperative eradication of potential agents of infection (eg, gonorrhea, chlamydia, bacterial vaginosis). OUTCOME AND PROGNOSISDisease eradication and recurrence rates following carbon dioxide laser therapy are often compared with those following cold-knife conization procedures or LEEPs. Outcomes are compared with the assumption that similar preprocedural evaluations (eg, Papanicolaou test, colposcopy, biopsies) have been performed. Carbon dioxide laser procedures eradicate CIN in up to 90% of cases.19 However, because of the physiology of the HPV, an operative procedure results in a reduced viral load and the excision of overtly diseased tissue, but it does not completely eradicate the virus from the host. Complete eradication is a function of the patient's immune system. A randomized trial of cryotherapy, carbon dioxide laser vaporization, and a LEEP for CIN reveals relatively equal rates of disease persistence and recurrence after each of the modalities, with follow-up periods from 6-37 months. Recurrences are more likely to occur in older women (aged 30 y 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.12 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.15 Women infected with HIV have a higher prevalence of CIN than those who are not infected. This is presumably related to coexistent HPV infection and immune function in these patients. Current care recommendations include more frequent surveillance of cervical cytology and more aggressive management using colposcopy, biopsy, and treatment of CIN. Dysplasia has been noted to recur more often in HIV-positive patients, despite a variety of dysplasia treatment modalities, including carbon dioxide laser procedures. Evaluation of patients with recurrent disease may reveal decreased CD4 counts and increased viral loads.20 One study cited a relative risk for recurrence of 17.517 after standard therapy with negative margins.21 This high risk has resulted in recommendations for excisional therapy rather than ablation22, 23, although excision also carries a higher risk for recurrent disease in the presence of compromised immune status. Even after hysterectomy, HPV infection and neoplasia development are still possible.21 On a more positive note, in immunologically intact women, appropriate dysplasias treated with carbon dioxide laser procedures may result in complete eradication of the HPV genome. In a study by Kjellberg et al, cervical dysplasias ranging from mild to severe were evaluated and documented based on colposcopy and/or 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.24 FUTURE AND CONTROVERSIESThe 2001 Bethesda Workshop reaffirmed ASCUS as the designation for squamous atypias that cannot be readily designated as benign or preinvasive. The only subcategory of ASCUS is now ASCUS favoring high-grade SIL. All other prior subsets are now combined under ASCUS, and reflex HPV testing is recommended when the lesion is deemed present after cytologic interpretation. HPV-negative ASCUS is a high-grade SIL or worse in fewer than 1% of cases.25 The results of colposcopy and those of HPV typing have equivalent sensitivity, and both help detect cervical dysplasia that requires treatment, including carbon dioxide laser procedures. The appropriate long-term follow-up protocol for women with high-risk HPV types and those with unclassified HPV types remains unknown. The most reasonable course of long-term follow-up is not yet determined. REFERENCES
Carbon Dioxide Laser Surgery for Cervical Dysplasia excerpt Article Last Updated: Dec 5, 2007 |