Introduction

Essentials of Diagnosis

 
• The presumptive diagnosis is made by an abnormal Pap smear of an asymptomatic woman with no grossly visible cervical changes.  
• Diagnose by colposcopically directed biopsy.  
• Increased in women with HIV.

General Considerations

The squamocolumnar junction of the cervix is an area of active squamous cell proliferation. In childhood, this junction is located on the exposed vaginal portion of the cervix. At puberty, because of hormonal influence and possibly because of changes in the vaginal pH, the squamous margin begins to encroach on the single-layered, mucus-secreting epithelium, creating an area of metaplasia (transformation zone). Factors associated with coitus (see Prevention, below) may lead to cellular abnormalities, which over a period of time can result in the development of squamous cell dysplasia or cancer. There are varying degrees of dysplasia (Table 17-2), defined by the degree of cellular atypia; all types must be observed and treated if they persist or become more severe. At present, the malignant potential of a specific lesion cannot be predicted. Some lesions remain stable for long periods of time some regress, and others advance.

Clinical Findings

There are no specific symptoms or signs of cervical intraepithelial neoplasia. The presumptive diagnosis is made by cytologic screening of an asymptomatic population with no grossly visible cervical changes. All visibly abnormal cervical lesions should be biopsied.

Diagnosis

A. Cytologic Examination (Papanicolaou Smear)
Specimens should be taken from a nonmenstruating patient, spread on a single slide, and fixed or rinsed directly into preservative solution if a thin layer slide system (ThinPrep) is to be used. A specimen should be obtained from the squamocolumnar junction with a wooden or plastic spatula and from the endocervix with a cotton swab or nylon brush.

Cytologic reports from the laboratory may describe findings in one of several ways (see Table 17-2). While use of class I-IV is now rare, the CIN classification continues to be used along with a description of abnormal cells, including evidence of human papillomavirus (HPV). The Bethesda System uses the terminology “squamous intraepithelial lesions (SIL),” low-grade or high-grade. Cytopathologists consider a Pap smear to be a medical consultation and will recommend further diagnostic procedures, treatment for infection, and comments on factors preventing adequate evaluation of the specimen. Reflex HPV testing of thin layer cytologic smears may be useful for triage of atypia (atypical squamous cells of unknown significance; ASC-US).

B. Colposcopy
Viewing the cervix with 10-20× magnification allows for assessment of the size and margins of an abnormal transformation zone and determination of extension into the endocervical canal. The application of 3-5% acetic acid (vinegar) dissolves mucus, and the acid’s desiccating action sharpens the contrast between normal and actively proliferating squamous epithelium. Abnormal changes include white patches and vascular atypia, which indicate areas of greatest cellular activity. Paint the cervix with Lugol’s solution (strong iodine solution [Schiller’s test]). Normal squamous epithelium will take the stain; nonstaining squamous epithelium should be biopsied. (The single-layered, mucus-secreting endocervical tissue will not stain either but can readily be distinguished by its darker pink, shinier appearance.)

C. Biopsy
Colposcopically directed punch biopsy and endocervical curettage are office procedures. If colposcopic examination is not available, the normal-appearing cervix shedding atypical cells can be evaluated by endocervical curettage and multiple punch biopsies of nonstaining squamous epithelium or biopsies from each quadrant of the cervix.

Data from both cervical biopsy and endocervical curettage are important in deciding on treatment.

Prevention

Current data suggest that cervical infection with the human papillomavirus (HPV) is associated with a high percentage of all Cervical dysplasias and cancers. There are over 70 recognized HPV subtypes, of which types 6 and 11 tend to cause mild dysplasia, while types 16, 18, 31, and others cause higher-grade cellular changes.

Cervical cancer almost never occurs in virginal women; it is epidemiologically related to the number of sexual partners a woman has had and the number of other female partners a male partner has had. Use of the diaphragm or condom has a protective effect. Long-term oral contraceptive users develop more dysplasias and cancers of the cervix than users of other forms of birth control, and smokers are also more at risk. Preventive measures include regular cytologic screening to detect abnormalities, limiting the number of sexual partners, using a diaphragm or condom for coitus, and stopping smoking.

Women with HIV infection appear to be at increased risk of the disease and of recurrent disease after treatment. Women with HIV infection should receive regular cytologic screening and should be followed closely after treatment for cervical intraepithelial neoplasia.

Because of the very low rate of abnormal Papanicolaou smears in women who have undergone hysterectomy for benign disease, routine screening is not justified in this population.

Treatment

Treatment varies depending on the degree and extent of cervical intraepithelial neoplasia. Biopsies should always precede treatment.

A. Cauterization or Cryosurgery
The use of either hot cauterization or freezing (cryosurgery) is effective for noninvasive small lesions visible on the cervix without endocervical extension.

B. CO2 Laser
This well-controlled method minimizes tissue destruction. It is colposcopically directed and requires special training. It may be used with large visible lesions. In current practice it involves the vaporization of the transformation zone on the cervix and the distal 5-7 mm of endocervical canal.

C. Loop Resection
When the CIN is clearly visible in its entirety, a wire loop can be used for excisional biopsy. Cutting and hemostasis are effected with a low-voltage electrosurgical machine (Bovie). This office procedure with local anesthesia is quick and uncomplicated.

D. Conization of the Cervix
Conization is surgical removal of the entire transformation zone and endocervical canal. It should be reserved for cases of severe dysplasia or cancer in situ (CIN III), particularly those with endocervical extension. The procedure can be performed with the scalpel, the CO2 laser, the needle electrode, or by large-loop excision.

E. Follow-up
Because recurrence is possible - especially in the first 2 years after treatment - and because the false-negative rate of a single cervical cytologic test is 20%, close follow-up is imperative. Vaginal cytologic examination should be repeated at 3-month intervals for at least 1 year.
Preferences
Sawaya GF et al: Current practice. Current approaches to cervical-cancer screening. N Engl J Med 2001;344:1603.

Sherman ME et al: Effects of age and human papilloma viral load on colposcopy triage: data from the Randomized Atypical Squamous Cells of Undetermined Significance/Low-grade Squamous Intraepithelial Lesion Triage Study (ALTS). J Natl Cancer Inst 2002;94:102.

Stoler MH: New Bethesda terminology and evidence-based management guidelines for cervical cytology findings. JAMA 2002;287:2140.

Wright TC Jr et al: 2001 Consensus guidelines for the management of women with cervical cytological abnormalities. JAMA 2002;287:2120.