As described previously, the first step in the workup of CSIL is performance of cervical cytology. If an abnormal cytology has been obtained, the two major decision points in the management algorithm for treatment of CSIL are (1) whether or not to perform colposcopy and (2) whether or not treat a cervical lesion once it has been biop-sied and the histopathology of the lesion has been established. A number of different organizations have published guidelines for cervical cytology screening in women. The American College of Obstetricians and Gynecologists and the American Cancer Society recommend that all women begin yearly Pap tests at age 18 or when they become sexually active, whichever occurs earlier. If a woman has had three consecutive negative annual cytology tests, testing may be performed less often at the judgment of a woman's health care provider.
Guidelines for management of women with abnormal cervical cytology have been established by the National Cancer Institute (9). Currently women with ASCUS undergo repeat cytology every 4-6 mo for 2 yr until there have been three consecutive normal smears. If ASCUS is found in conjunction with an inflammatory process, then diagnostic measures to identify and treat concurrent vaginal infections should be initiated before the cytology is repeated. Most clinicians would perform colposcopy if a second ASCUS cytology is found within that 2-yr period. If LSIL is diagnosed on cytology, a similar follow-up plan may be initiated, but referral for colposcopy is recommended for women who may not return for follow-up. All women with HSIL on cytology should be referred for colposcopy.
Treatment of CSIL is based on the histology of biopsied lesions (CIN) and not on cytology (SIL), because of the inaccuracy of cervical cytology for grading lesions. Although treatment always is based on histology, the terms CIN and SIL often are used interchangeably. The purpose of performing biopsies is to determine if the lesions are low-grade or high-grade because the latter would mandate treatment, and to exclude the presence of invasive cancer, as this would invoke a different management algorithm. Several studies show that most biopsied lesions with mild (CIN 1) to moderate (CIN 2) dysplasia regress spontaneously with follow-up (78-81). Thus, although treatment of all cases of CIN 2 may not be necessary, it likely does prevent some cases of cervical cancer particularly among women who may be less likely to return for regular follow-up. Therefore, CIN 2 usually is combined with CIN 3 for the purposes of initiating therapy. Until recently it was the practice to treat all cases of CIN, including CIN 1. However, as the majority of CIN 1 regress spontaneously, many clinicians opt to follow women with CIN 1 rather than treat automatically.
Once a decision to treat CIN is made and biopsies have excluded invasion, there are a number of therapeutic options. Because there currently is no specific therapy for HPV infection, analogous to the use of acyclovir for treatment of herpes simplex virus infection, current treatment methods rely on ablation or removal of the lesion. The simplest method is local excisional biopsy if the lesion is small enough, but this method is inadequate if the lesion extends into the endocervical canal. More often other methods are required such as cryotherapy or large loop excision of the T zone (LLETZ). This procedure is also known as loop electrosurgical excision procedure (LEEP) (82-84). This procedure uses a fine wire to diathermically excise a cervical lesion or the entire transformation zone. The advantages of this procedure are that it preserves margins of the excised tissue for accurate pathologic assessment and is associated with less morbidity than other treatment methods (85,86). Morbidity is related to the amount of tissue removed and may include bleeding during or after the procedure and, rarely, cervical stenosis or cervical incompetence, which can lead to preterm delivery and low birth weight (87).
One of the disadvantages of LLETZ is that it is relatively expensive when compared to cryosurgery, which involves application of a liquid nitrogen cooled probe to the surface of the cervix (88-90). The probe is typically applied twice for 2-3-min applications and leads to necrosis of the frozen areas. The advantages of this method are its low cost, easy applicability in many different clinical settings, low morbidity, and treatment of the entire exocervix. Although reepithelialization of the cervix occurs within 2-3 mo, one of the disadvantages is that scarring may reduce the value of subsequent cytology and colposcopy, especially if the procedure leads to the recession of the squamocolumnar junction into the endocervix. The procedure has a higher failure rate than LLETZ; and it cannot be used if a woman has an inadequate colposcopy, positive endocervical curettage, or especially large lesions. In this case, the treatment of choice is LLETZ.
Laser conization using a CO2 laser is another treatment approach (91,92). Performed under colposcopic guidance, it has the advantage of allowing the clinician to precisely determine the depth of the lesion excision and leads to minimal damage to surrounding tissues. The laser coagulates blood vessels, and thus there is a lower risk of bleeding than with some of the other therapies. Healing typically occurs without the scarring associated with cryosurgery, and thus there is usually little difficulty with follow-up cytology and colposcopy.
Cold-knife conization can be performed with patients in an ambulatory surgery setting and is usually effective if the margins are negative. It is typically performed only if the patient cannot be treated with LLETZ or laser conization and is associated with a higher complication rate than the other procedures, including bleeding, stenosis, and scarring. Finally, hysterectomy can be performed if fertility is not a factor and if other gynecologic indications are present. Topical therapies such as retinoic acid and 5-fluo-rouracil have not been shown to be effective.
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