Recommendations for screening intervals

ACOG, AAFP, NCI, AMA, and ACS Recommendations (1988): (3)

• "...women who are, or have been sexually active, or have reached age 18 years, have an annual Pap test and pelvic examination.
• After a women has had three or more consecutive satisfactory normal annual examinations, the Pap test may be performed less frequently at the discretion of her physician."
• Decisions to perform the Pap smear less frequently should be based on a lack of cervical dysplasia risk factors.

The Pap smear is NOT indicated for the work-up of vaginal or cervical infections. There is a relative contraindication to Pap smears in the setting because of the inflammatory changes that occur in this setting that can give false positive smears.

Risk factors for developing cervical cancer.

• Three or more lifetime sexual partners...... Some say more than one...
• First sexual intercourse before age of 18
• Genital warts (papilloma virus) or other venereal diseases
• A sexual partner with condyloma or a history of genital warts
• A sexual partner who has had intercourse with a woman who developed cervical cancer, abnormal Paps, or had genital warts
• Smoking
• Maternal DES (diethylstilbesterol) exposure during pregnancy
• A previous abnormal Pap smear

I. Adequacy of the specimen

1. Satisfactory for evaluation
2. Satisfactory for evaluation but limited by ... (specify reason)
• Lack of endocervical cells in a premenopausal woman indicates that the collection of the cervical sample was less than ideal since adequate sampling of the os cannot be assured. This does not mean the sampling was not adequate or that the smear should be immediately repeated. (5) However, reliable follow-up is mandatory, and a repeat smear is indicated with any level of abnormality.
• Endocervical cells usually are not present in the cytology smears of post- menopausal women and do not indicate a need for additional testing. Clinicians should remember to note on path slips when women are post-menopausal.
3. Unsatisfactory for evaluation ... (specify reason)
• These smears should be repeated.

1. Benign cellular changes
2. No specific follow-up needed.
3. Infection consistent with Chlamydia, Trichomonas vaginalis, or Candida species
4. Treatment is usually indicated when causative organisms are identified. Consider further testing and/or treating.

1. Reactive cellular changes associated with inflammation (includes typical repair), atrophy with inflammation ("atrophic vaginitis")
2. Inflammation has been shown to have a low association with underlying CIN unless it is persistent. Many authors now recommend repeating such smears in 3 months after treating any potential sources of inflammation:
• Treat infection,
• Stop douching,
• Stop prolonged use of tampons, sponges, or diaphragms,
• Stop spermacide use,
• Use estrogen for 1 month in post-menopausal patients.
• If inflammation is persistent, colposcopy is indicated. (6-8)
3. Atrophic vaginal or cervical epithelium also may cause abnormal Papanicolaou smears. Colposcopists often prescribe estrogen for 2 to 4 weeks before a colposcopy in order to "normalize" the epithelium prior to the examination. This is generally felt to be safe even if dysplasia or cancer is present because the duration of therapy is short and these lesions do not express any more estrogen receptors than a normal cervix. (9)

Squamous cell It has become common practice in the United States for dysplastic Pap smears to be followed-up with colposcopy and directed biopsy to define the level of dysplasia or carcinoma present. (3, 10)

1. Atypical squamous cells of undetermined significance (ASCUS) (qualify)
• ASCUS or "Atypia" is a Pap smear result where there is strong controversy regarding implications and appropriate management. Most authors agree that there is a significant association between atypical smears and the presence of CIN, with studies showing dysplasia being present in 18% to 70% of cases (Figure 2). Some colposcopists recommend doing a colposcopy after only one atypical Pap smear even though studies have shown a low sensitivity for the Pap smear when used in this manner (Figure 3). Others will repeat the Pap and do a colposcopy after a second abnormal Pap. A rational approach is to consider the risk profile of your population or the risk factors of the patient when deciding whether to repeat the cytology or proceed to the definitive test.
2. Low-grade squamous intraepithelial lesion: HPV and mild dysplasia
• The regression rate of low-grade cervical squamous epithelial lesions has been found to range from 11% to 65% (Figure 4). The finding of high regression rates in some studies has lead to controversy over whether to treat or closely follow these lesions, and some authors advocate the use of a repeat Pap smear to follow-up those with low grade SIL. (7, 11 - 14) Many others recommend always using colposcopy to give a tissue diagnosis and define the extent of lesions. (2, 3, 8, 14 - 23)
3. Using the Pap smear to follow-up patients with previously abnormal low-grade Pap smears essentially changes the role of the test from that of a screening test for the presence of cervical dysplasia to a more definitive test to estimate high-grade histological lesions based on high-grade cytology (Figure 3). While the Pap smear has an adequate sensitivity for screening the general population for dysplasia, it is not sensitive enough to be considered a definitive test. General assumptions concerning screening the general population may not be accurate when it is used as a definitive test to separate high-grade from non-high-grade histological lesions.
• In the LSUMC study, 68% of the patients with biopsy proven high-grade lesions actually had low-grade cytology on their initial Pap smears. 24 When their Pap smears were repeated, 87% still did not have high-grade cytology and 23% of these repeat pap smears were normal. If these patients had been followed only with repeat Pap smears instead of colposcopy, it would have appeared that 23% of the lesions were regressing and most of the others would have been diagnosed as still having low grade-lesions, when in fact these patients had high-grade lesions that required treatment. "Monitoring patients with low-grade pap smears by using follow-up Pap smears is not advisable and is potentially dangerous because of the unacceptably low (25%) sensitivity of the follow-up Pap test. As with all screening tests, a definitive test such as colposcopy with appropriate management is necessary." (24)
4. High-grade squamous intraepithelial lesion: moderate / severe dysplasia and carcinoma-in-situ.
• Requires colposcopy to establish diagnosis and treatment.
5. Squamous cell carcinoma
• Requires colposcopy to establish diagnosis and start staging.

1. Endometrial cells, cytologically benign, in a postmenopausal woman
• No specific follow-up needed.
2. Atypical glandular cells of undetermined significance (qualify)
• Atypical glandular cells may be associated with endometriosis, endometrial hyperplasia, endometrial adenocarcinoma, and adenocarcinoma of the cervix. Adenocarcinoma of the cervix is rarer and often more aggressive than squamous cell disease, and colposcopy is indicated with atypical glandular cells.
3. Endocervical adenocarcinoma, Endometrial adenocarcinoma, Extrauterine adenocarcinoma, Adenocarcinoma
• Requires colposcopy to establish diagnosis and start staging.

Colposcopy Follow-up

I. Nondysplastic Findings

• Squamous metaplasia - normal finding, no treatment necessary.

• No specific treatment needed. The virus of the more carcinogenic strains inserts its DNA into the human genome, and thus elimination of all virus DNA is improbable. Therefore, over-aggressive treatment of koilocytic atypia could result in increased complications (especially with multiple treatments over time) without clear benefit. Yearly Pap smear surveillance is necessary because HPV infection is a risk factor for cervical dysplasia.

• With the high regression rate of CIN 1, patients can be followed with serial colposcopy or Pap smears alternating with colposcopy if adequate follow-up can be assured. (25)

• CIN 2 and 3 are usually treated.

• Be especially concerned if the biopsy reports are significantly less than Pap cytology. For instance, a Pap smear indicating carcinoma-in-situ and biopsies of only mild dysplasia could signify that the worst area of dysplasia was not biopsied. In general, a difference of one grade (i.e., impression = CIN 2 and biopsy = CIN 3) is common and acceptable.
• Do not ablate any cervix until you have adequately and sufficiently explained any significant discrepancy between histology and cytology. If the discrepancy cannot be explained, repeat colposcopy or conization is indicated. (26) Repeating colposcopy is forgivable, even in the hands of the best. Freezing invasive cancer is not.

• Cone biopsy (cold cone, laser, or LEEP cone) is indicated if the endocervical curettage sample reveals dysplasia or the colposcopy is not adequate. "Positive" ECCs are sometimes a result of contamination with dysplastic lesions at the verge of the os, but do not assume this!

Treatment for Cervical Dysplasia

I. Cryotherapy

Candidates for outpatient cervical cryotherapy are patients with smaller CIN 1 or 2 lesions that do not enter the cervical os. Large lesions (over 1" in diameter, more than 1/2" from the os, or involving more than two cervical quadrants), even if they are only mild dysplasia, may be more appropriate loop or laser therapy candidates than a small focal severe dysplasia that may respond very well to ambulatory cryotherapy. (25)

II. LEEP

Candidates for LEEP or laser of the transformation zone include patients with any grade of dysplasia with an adequate colposcopic exam. Larger lesions and lesions that enter the cervical os more than 4 mm are most appropriately treated with LEEP or laser therapy. Since CIN 3 / CIS lesions tend to have more deep crypt involvement, LEEP is the preferred treatment modality since the depth of cut may be observed and controlled, and the margins of the treatment can be checked histologically. Be cautious with lesions that extend far laterally on the ectocervix because it is difficult to obtain an adequate depth of cut in these lesions.

III. Choosing therapy

Most lesions found will fit the criteria for treatment with either cryotherapy or LEEP. Cryotherapy is fast and technically easy with less expensive equipment and minimal set-up time. LEEP gives the advantage of greater precision of depth of treatment and histologic specimen for analysis. Both methods have similar cure rates for CIN 1 and 2. Which treatment modality to use is often a matter of personal preference.

IV. Conizations

A must with inadequate colposcopies or positive colposcopies.

Consider OR conization for very extensive or deep lesions and also for recurrent lesions after treatment.

V. Treatment follow-up

4- to 6-month intervals for 2 years, with colposcopy or colposcopy interspersed with Pap smears. Recurrence is most common in the first 2 years after therapy. Recurrences are most common in the os and on the outside margins. A positive margin on a LEEP specimen requires close colposcopic follow-up.

Conclusion:

Our understanding and ability to diagnose and treat cervical disease has increased greatly in the last half-century. However, many controversies still exist about the best way to follow-up some Pap smears and approach the treatment of some patients. With good knowledge of cervical pathology and the patients being tested, good decisions can be made in order to take the best care possible of the women in our practices.

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