WHAT'S NEW IN CERVICAL DYSPLASIA


Introduction

A review of pertinent, new articles on related topics.
  1. Rising rates of cervical adenocarcinoma.
  2. Atypical glandular cells of undetermined significance.
  3. Clinical characteristics of adenocarcinoma of the cervix.
  4. Management of adenocarcinoma-in-situ of the cervix.
  5. Does Pap smear technique influence endocervical cell yield?
  6. Should an ECC be performed at cervical LEEP conization?
  7. My favorite reviews for HPV.
  8. The effect of educational brochures on colposcopy.
  9. Does nutrition play a role in cervical dysplasia?
  10. ECC or the cytobrush?
  11. Pain control for LEEP and colposcopy.
  12. Anal dysplasia in HIV-positive women.
  1. Rising rates of cervical adenocarcinoma.

    2. Dr. Michael Campion recently reported that adenocarcinoma comprised 5% to 15% of invasive cervical cancer three decades ago, but now accounts for 20% to 30% in recent reports. (Prim Care Cancer 1993; 13:22.) This trend reflects both the improved detection of glandular disease, and that there is a true increase in its incidence. Glandular neoplasia is associated with HPV-18. Since glandular carcinoma-in-situ is uncommon, it appears that glandular premalignant disease rapidly progresses to invasive disease. Oral contraceptive use has been associated with cervical adenocarcinoma (Ursin G, Lancet 1994; 344:1390-1394).
  2. Atypical glandular cells of undetermined significance.

    3. AGUS should be subclassified when talking about endocervical cells, if possible, as favoring a benign or neoplastic process (Kurman RJ, JAMA 1994; 271:1866-1869). Such subclassification is not possible for AGUS that involves endometrial cells. If the cytology is suspicious for adenocarcinoma, the endocervical canal is best evaluated by cone biopsy. The best way to evaluate unclassified AGUS is unclear. Some practitioners advocate repeat cytobrush and endometrial biopsy, but this method can miss rapidly developing adenocarcinoma. Persistent findings of AGUS that are not reconciled by other evaluations require the performance of a cone biopsy.
  3. Clinical characteristics of adenocarcinoma of the cervix.

    4. The detection of cervical adenocarcinoma and its precursors are a challenge to the clinician. Most invasive and in-situ adenocarcinomas occur in older women with inward migration of the SCJ (squamocolumnar junction) (Kjaer SK and Brinton LA, Epidemiol Reviews, 1993; 15:486-498). Most adenocarcinomas grow endophytically and are less likely to be detected. Adenocarcinoma-in-situ is considered to be a relatively rare condition. Adenocarcinoma-in-situ can occur beneath the TZ (transformation zone), and may be covered by normal, metaplastic, or dysplastic epithelium. Fifteen percent (15%) of women have multicentric adenocarcinoma-in-situ. It appears that HPV 18 is strongly linked to cervical adenocarcinoma, rather than HPV 16, which is strongly linked with cervical squamous cell carcinoma. Both adenocarcinoma and squamous cell carcinoma (or precursors) may be found to be coexisting.
  4. Management of adenocarcinoma-in-situ of the cervix.

    5. The management of adenocarcinoma-in-situ (ACIS) of the cervix remains controversial. In the past, hysterectomy was recommended as the treatment of choice. However, since many women with ACIS are in the childbearing years, more conservative management has been proposed. Is conization adequate? Poynor's experience at Memorial Sloan-Kettering Cancer Center raises concerns about conization as the optimal management of ACIS (Gynecol Oncol 1995; 57:158-164). To begin, the colposcopic ECC detected glandular disease in only 43% of patients with biopsy-proven ACIS. Disease recurred in nearly one-half of patients after conization, and 13% had invasive adenocarcinoma develop. A negative conization margin was not reassuring, since ACIS is a multicentric disease. Hysterectomy may be a better option.
  5. Does Pap smear technique influence endocervical cell yield?

    6. The sequence of endocervical sampling when obtaining a Pap smear can influence the yield of endocervical cells. Noel's group found the greatest yield when endocervical sampling was performed first with a straight endocervical brush, followed by ectocervical sampling with a spatula (J Am Board Fam Pract 1993; 2:103-107). The brush may stir up endocervical cells into the mucous that are retrieved by the spatula.
  6. Should an ECC be performed at cervical LEEP conization?

    7. The ECC is not always performed to evaluate the remaining endocervical canal following conization. Kobak's group evaluated patients with a positive ECC, or a positive histologic margin, at the time of cervical conization (Obstet Gynecol 1995; 85:197-201). Kobak's study demonstrated that patients with the ECC positive for dysplasia at the time of conization had a significantly higher risk of invasive cancer than if the ECC was negative. Older patients (over 50 years of age) were particularly at risk, and should be considered for repeat conization or hysterectomy if the ECC or conization margins are positive.
  7. My favorite reviews for HPV:
  8. The effect of educational brochures on colposcopy.

    9. Psychological distress frequently occurs in women who are notified of an abnormal Pap smear result. Many women worry that they have cancer, and their distress may interfere with their sexuality or relationship with their partner. Stewart and associates mailed patients an educational brochure on dysplasia and abnormal Pap smears (Obstet Gynecol 1993; 81:280-2). Women who received the brochure had less anxiety and distress, and they were more knowledgeable about dysplasia and colposcopy at the time of colposcopic examination. The authors recommend that an educational brochure be sent any time a patient is notified of an abnormal Pap smear result. Women also prefer doctor-initiated notification of their Pap smear results, rather than having to call themselves (Schofield MJ, Prevent Med 1994; 23:276-283).
  9. Does nutrition play a role in cervical dysplasia?

    10. Butterworth demonstrated that low red blood cell folate levels enhance the effect of other risk factors for cervical dysplasia, especially that of HPV 16 infection (JAMA 1992; 267:528-533). Palon showed that the antioxidants b-carotene and a-tocopherol have biologic functions that inhibit the development of CIN (Nutr Cancer 1991; 15:13-20). We recommend that all our patients evaluated by colposcopy consume five servings of fresh fruits and vegetables daily. If younger patients can't do this, we recommend a multivitamin with antioxidants. Enhanced nutrition is believed to improve the immune system response in the cervix. An enhanced immune response may aid in the elimination of cervical dysplasia (Fukuda K, Obstet Gynecol 1993; 82:941-5).
  10. ECC or the cytobrush?

    11. Dr. Kenneth Noller, noted colposcopy teacher, says it best (Colposcopist 1994; 26:1-2): "In virtually every study the accuracy of the brush has been much greater than that of the ECC. While the literature is evolving, most practitioners have ceased performing old-fashioned ECCs and are now using an endocervical brush at the time of colposcopy to evaluate the endocervix. At the last three courses I attended, I specifically asked the audience how they evaluate the endocervix. In each case, more than 80% of the participants indicated they no longer use an endocervical curette; they use a brush."
  11. Pain control for LEEP and colposcopy. Anesthesia for the LEEP procedure generally consists of intracervical administration of 1% lidocaine with epinephrine. Since many patients report that the injection is the most uncomfortable part of the procedure, Lipscomb's group tried to apply 20% benzocaine (Hurricaine) gel to reduce the pain of injection (Am J Obstet Gynecol 1995; 173:772-4). The pain scores were low with and without the benzocaine, so this topical therapy was not deemed beneficial for LEEP. Patients undergoing colposcopy may complain of pain from the ECC or biopsies. We premedicate all patients undergoing colposcopy with ibuprofen (Advil) 3 to 4 tablets 1 to 1 1/2 hour before the procedure. The ibuprofen assists with the uterine cramping associated with the ECC. Since up to 10% of patients may bitterly complain of pain associated with cervical biopsies, we have used 20% benzocaine spray (Beutlich Pharmaceuticals, Niles, Illinois) to anesthetize the cervix. I have been greatly impressed with the results: patient reports have been terrific. Rabin's group demonstrated benefit of topical benzocaine for cervical biopsy, IUD insertion, ECC, and tenaculum placement (Obstet Gynecol 1989; 73:1040-1044). Some practitioners will reduce patient pain by using smaller biopsy forceps (Baby Tischlers). The baby forceps do reduce discomfort, but also take a smaller bite and may produce sampling error.
  12. Anal dysplasia in HIV-positive women.

    13. HPV infection produces multicentric disease in the genital tract of women. Nineteen percent (19%) of women with high-grade CIN were noted to have concomitant anal lesions (Scholenfield JH, et al, Lancet 1992; 340:1271-3). Anal Pap smears can be used to detect anal disease, with a moistened Dacron swab inserted 4 cm up to the anorectal junction. Williams' study from San Francisco showed that HPV DNA could be retrieved twice as often from the anus as from the cervix in HIV-seropositive women (Obstet Gynecol 1994; 83:205-11). Should the anal Pap smear become a routine screening test for HIV-positive men and women? Should all HIV-positive individuals undergo frequent anoscopic examinations?