The mean age of the 55 adolescents in the HSIL cohort was 16.9 years and ranged from 12–18 years (Table 1). The median follow-up for the HSIL subjects was 16.0 months. Seventeen (30.9%) of the HSIL adolescents underwent an excisional procedure during the study interval. Follow-up cervical cytology alone was available for 5 (9.1%) of the adolescents, whereas a histologic specimen was obtained from 50 (90.9%) patients (Table 2). The histologic sample was reported as negative in 13 (26%), as CIN 1 in 10 (20%), CIN 2 in 13 (26%), and CIN 3 in 13 (26%). One 18-year-old was found with adenocarcinoma in situ on a cervical biopsy (Table 2). The cytologic and histologic follow-up of the adolescents with HSIL were then combined, and the most severe abnormality was recorded. A similar classification as was used for the adolescents with LSIL was then applied. Negative follow-up was documented in 12 (21.8%) adolescents, whereas 15 (27.3%, 15.5–39.0%) adolescents had low-grade abnormalities. Over one half of the adolescents (50.9%, 37.7–64.1%) with an initial Pap test reported as HSIL were subsequently found to have a high-grade abnormality. At 12 months after the index HSIL cytologic sample, 24% of the subjects had progressed to biopsy-confirmed CIN 3. After 36 months of follow-up, the rate of progression to CIN 3 had increased to 31%.
Our findings reveal that adolescents with squamous intraepithelial lesions of the cervix are at substantial risk for the development or persistence of high-grade cervical intraepithelial neoplasia. Recent population-based studies have indicated that the incidence of cervical cytologic abnormalities among adolescents is rising. In 1981 Sadeghi et al14 noted that the rate of dysplasia among more than 190,000 adolescents aged 15–19 years was 1.9%. Two decades later, Mount and coworkers6 reviewed 10,296 Pap tests in adolescents 10–19 years old and reported SIL in 3.7% and ASC-US in 9.8%. Among adolescents, the rate of ASC-US ranges from 7–16%, LSIL from 3–13%, and HSIL from 0.2–3%.5–7,10,15,16 The dramatic increase in the incidence of cervical abnormalities among adolescents is likely multifactorial, related primarily to increasing rates of sexual activity and HPV infection in this age group.8–11 The prevalence of HPV infection in sexually active adolescents is 20–43% and is highly dependent on the population studied.11,17 Our findings of LSIL in 5.7% and HSIL in 0.7% of the adolescents at our institution are in accord with previously published work.
Although the outcomes of adult women with cervical cytologic abnormalities have been well characterized, a paucity of data exists to describe the outcome of teenagers with cervical dysplasia.5,7,18 Economos et al18 reviewed 315 adolescents aged 14–19 with LSIL and HSIL cytology. Among the LSIL subjects, 47% had negative follow-up, 49% had mild abnormalities, and 3% had CIN 2 or 3. The corresponding rates for the HSIL cohort were 10%, 4%, and 86%, respectively. Overall, 35% of our subjects with LSIL cytology had negative follow-up, 47% had low-grade lesions, and 18% had high-grade abnormalities. For our HSIL cohort, follow-up was negative in 22%, revealed low-grade lesions in 27%, and high-grade abnormalities in 51%.
Perhaps the most important question addressed by the present study is whether a difference exists in the outcome of adolescents and adults with cervical dysplasia. In adult women with LSIL, 15–30% of those evaluated with cervical biopsy will be found to have CIN 2 or 3.4,19,20 In our cohort of LSIL patients who underwent biopsy, 23.6% had high-grade lesions, 13.6% with CIN 2 and 10% with CIN 3. Among adult women with HSIL cytology who undergo biopsy, 40–75% will have CIN 2 or 3 and 1–2% will have invasive neoplasms.3,4,19 Fifty-two percent of our HSIL subjects with histologic follow-up had CIN 2 or 3. To determine the natural history of cervical squamous intraepithelial lesions in adult women, Melnikow and colleagues21 performed a meta-analysis that included nearly 28,000 women. In their pooled analysis, after 24 months of follow-up 47% of women with LSIL had regressed to normal while 21% had progressed to a higher-grade lesion. The pooled analysis for women with HSIL revealed a regression rate of 35% and progression to CIN 3 in 23% of the women.21 In a cohort of women aged 13–22 years with LSIL, Moscicki et al22 noted that 61% of the women had regressed by 12 months, whereas 91% had regressed after 36 months of follow-up. In our cohort of LSIL subjects, 28% had regressed by 12 months, 55% had regressed by 24 months, and 62% had regressed after 3 years of follow-up. For our HSIL subjects 31% had progressed to biopsy-proven CIN 3 by 24 months of follow-up. Thus, our findings indicate that the natural history of cytologic abnormalities in adolescents is similar to adults.
The optimal timing and method of cytologic screening in adolescents remains to be determined. The American Cancer Society now recommends initiation of cervical cancer screening 3 years after vaginal intercourse, no later than 21 years of age.23 Given the presumed high rate of resolution of low-grade lesions in adolescents, the recommendation was implemented to avoid detection and treatment of clinically insignificant lesions. Similar recommendations have been put forth by other groups.24 The American Society for Colposcopy and Cervical Pathology guidelines for the management of women with cytologic abnormalities suggest that in adolescents with LSIL, follow-up cytology at 6 and 12 months may be appropriate in lieu of immediate colposcopy as proposed for adults. The panel suggests that colposcopic observation is appropriate in selected young, reproductive-age women when biopsy-confirmed CIN 2 or 3 is not identified.4 These guidelines are based on the knowledge that invasive cervical cancer is exceedingly rare in adolescents.25 Although our findings revealed a higher than expected rate of high-grade cervical abnormalities, no cases of invasive cancer were detected in our cohort.
The present study has the advantage of having evaluated nearly 650 consecutively collected cytologic specimens from adolescents. However, consistent with prior studies of cervical dysplasia and the retrospective nature of the report, follow-up was not available for the entire cohort. Additionally, diagnosis and management of the subjects was not standardized and was at the discretion of each participant’s physician. Finally, on a subset of the study population, only cytologic follow-up was available. Cytologic follow-up alone is commonly used for the follow-up of adolescents with cervical dysplasia. Thus, the lack of histologic correlation is not surprising and reflects the current practice patterns used for adolescents with dysplasia.
Our findings reveal that adolescents with LSIL and HSIL cytology are at significant risk for the development of high-grade cervical abnormalities. Overall, 18% of teenagers with LSIL and 51% with HSIL were eventually found with a high-grade lesion. These rates are similar to those previously reported in adult populations. Thus, adolescents with cytology reported as SIL carry a similar risk for underlying cervical intraepithelial neoplasia as adults. Although these findings help to define the underlying risk of CIN in adolescents with SIL, the natural history of biopsy-confirmed CIN 2 and 3 in adolescents remains poorly defined and is currently under investigation. Based on limited data, it has been suggested that CIN in adolescents is more likely to regress without treatment. Although less intensive intervention for adolescents with LSIL and HSIL certainly seems reasonable, these adolescents are still at considerable risk and warrant close follow-up. Contraceptive counseling at the time of follow-up would certainly seem prudent. Prospective studies to evaluate alternative management strategies for adolescents with LSIL and HSIL are clearly warranted.
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