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Management of Atypical Pap Smears - 2001
Conference Report Autumn in New York 2001: Controversies in Gynecology November 12-13, 2001 Montefiore Medical Center, Bronx, NY Mark D. Levie, MD ztaženo z www.medscape.com Management of Atypical Pap Smears Since widespread screening with the Papanicolau smear began in the United States, cervical cancer rates have markedly decreased.[4] It is estimated that since 1973, the incidence of cervical cancer and its associated mortality have both decreased by 40% to 50%. Worldwide, however, cancer of the cervix is still one of the most common malignancies in women. Even in the United States, it is estimated that there will be 12,900 new cases of cervical cancer diagnosed in 2001, with approximately 4400 deaths related to this disease.[5] An important point stressed at the meeting before the conversation about the management of atypical pap smears was that the majority of cervical cancers diagnosed in the United States occur in the 15% of the population who have not undergone screening in the previous 5 years. In an interesting study using the Connecticut Tumor Registry, Janerich and colleagues[6] reviewed the Pap smears and biopsies of patients subsequently diagnosed with cervical cancer; the investigators found that 29% of the patients had never been screened and that 23% had not had a Pap smear within the 5 years prior to their diagnosis. Therefore, if we really want to continue to decrease the incidence of cervical cancer, our energy and resources may be best spent on increasing our screening population rather than improving our technology. Overview Over 50 million Pap smears are done in the United States each year, 2 million of which are reported as atypical. The 2001 Bethesda System defines atypical squamous cells (ASC) as cytologic changes suggestive of a squamous intraepithelial lesion (SIL) that are quantitatively or qualitatively insufficient for a definitive interpretation. ASC was subdivided into 2 categories: ASC of undetermined significance (ASCUS) and ASC for which the presence of high-grade SIL cannot be excluded (ASCH). Approximately 60% of patients with an ASC Pap result will have normal histology; 5% to 15% of patients will have cervical intraepithelial neoplasia (CIN) II-III on biopsy. The ASC rate is generally < 5% or 2-3 times the dysplasia rate in the population.[7] ASCUS rates increase with prevalence of dysplasia. New Cytologic Adjuncts Conventional Pap smear screening has been effective in reducing the incidence of cervical cancer. However, a study commissioned by the American College of Obstetrics and Gynecology to evaluate cytologic screening methods showed that the sensitivity of a single Pap smear is only about 51%.[8] Although there were limited data to assess newer technologies, the study suggested that liquid-based cytology can increase sensitivity by 60%. Liquid-based cytology is thought to have several advantages over the conventional Pap smear. Given the natural history of cervical disease, increased detection of low-grade disease and more ASCUS smears detected by liquid-based cytology would not necessarily be an advantage. However, several recent studies have shown that this technique increases detection of significant disease, ie, CIN II-III.[9,10] Furthermore, there is a decrease in Pap smears that, although satisfactory, are limited by obscuring inflammation or blood. Liquid-based mediums also allow testing for human papillomavirus (HPV), gonorrhea, and Chlamydia. Management Options Three basic algorithms were outlined by Dr. Erica Banks, Assistant Professor, Obstetrics and Gynecology, Albert Einstein College of Medicine/Montefiore Medical Center, to deal with the management of an atypical Pap smear. Repeating cervical cytology at specific intervals HPV DNA testing for high-risk types Immediate colposcopy Repeat cytology. Repeating cervical cytology has long been the way physicians have managed their patients with an atypical Pap smear. If a second Pap smear revealed ASCUS, the patient would undergo colposcopy; this procedure is more clinically effective and cost-effective than repeating the Pap smear a third time. If the result of repeat cytology is negative, cytology would then be repeated every 4-6 months. A repeat Pap smear that is negative 2 consecutive times is a more sensitive indicator than an immediate negative result obtained with colposcopy. After 2 negative Pap smears, the patient can return to a yearly screening regimen. The criticism of this management scheme is that repeat conventional cytology only has an approximate 70% sensitivity for detecting CIN II-III disease[11] (Of note is that repeat liquid-based cytology had an 85% sensitivity for detecting CIN II-III in the ASCUS/Low-grade Squamous Intraepithelial Lesion Triage [ALTS] Study[12]). In addition, there is always the concern regarding patient compliance and follow-up. A further criticism is the cost of time and resources to have the patient come in a second time for another office visit to repeat the Pap and the associated worry the patient will experience in the interval. HPV DNA reflex testing for high-risk types. In 1995, the World Health Organization identified HPV types 16 and 18 as causative agents for cervical cancer. This was based on extensive testing of cases of cervical cancer from around the world that detected high-risk HPV strains in 99.7% of cases.[13] A sensitive, commercially available assay (Hybrid Capture II) has been developed to screen for HPV. Using liquid-based cytology, patients with atypical Pap smears can have the residual fluid then tested for the presence of high-risk HPV types. The National Cancer Institute is currently conducting a study called the ALTS trial. This trial was designed to evaluate the 3 management options mentioned earlier (repeat Pap, colposcopy, and HPV testing). The preliminary data have been analyzed and published by Solomon and associates.[12] HPV testing was not determined to be efficacious in patients with low-grade SIL on PAP, as 83% were HPV positive. In the patients with ASCUS Pap smears, preliminary data show that the Hybrid Capture II was 96% sensitive in detecting patients with high-grade SIL. Furthermore, the negative predictive value is 98%, meaning that when an HPV test result is negative, the physician can be confident in reassuring the patient that she does not have significant disease. Further Analysis of the ALTS Data First, it must be made clear that this study was designed as a 2-year follow-up study, and while preliminary data seem to show excellent sensitivity for the HPV arm and a poorer one for the conservative management arm, this will likely change during the follow-up as more cases of CIN II/III are identified by repeat Pap smears in the conservative arm. One of the major criticisms of HPV reflex testing is the number of colposcopies done in this group as compared with the conservative arm, 56% vs 7%. However, only patients with high-grade SIL were sent for colposcopy. If the repeat Pap smear revealed ASCUS or more serious cytology -- the criteria used by most clinicians as the diagnosis for referral to colposcopy -- 58% would need colposcopy, an equivalent proportion as for the HPV arm. The Role of Immediate Colposcopy and ASCUS HIV-positive patients with Pap smears revealing ASCUS have a 4 times higher prevalence of CIN II-III and therefore should be referred directly for colposcopy.[14] Similarly, with the new Bethesda Categorization, it seems that immediate colposcopy may be warranted in patients in the ASCH group, as 24% to 94% have CIN II-III.[8,15-18] Furthermore, patients who are poorly compliant or have a prior history of preinvasive disease should be referred directly for colposcopy. Conclusions Questions about HPV testing must be answered, the most important of which are the following: Will HPV testing be superior to following patients with ASCUS Pap smears every 4-6 months with cytology and colposcopy when indicated? Will it lead to the diagnosis of more women with high-grade SIL lesions than cytology and increase detection of cervical cancer? Currently, either management plan is accepted practice and can be individualized to the patient and provider. The most important requirement is getting all patients in for screening, as most cancer occurs in the unscreened.


 Pojišťovny a poskytovatelé/Zdravotnická zařízení/: Management of Atypical Pap Smears - 2001
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