Examining the Evidence
Is excision required in adolescents with CIN 2 or higher on cervical cytology?
Not necessarily. In this chart review, 29% of adolescents with biopsy-proven cervical intraepithelial neoplasia (CIN) grades 2 or 3 opted for conservative treatment rather than excision. Over 18 months, the condition regressed in 65% of these patients, remained stable in 20%, and progressed without cancer in 5%. No invasive cancers developed.
Overall, CIN 2,3 was present in 35% of adolescent patients referred to colposcopy for cervical dysplasia.
Adolescents differ from adults in many ways—no surprise. Some of the less obvious differences are their tendency to have multiple sexual partners, which exposes them to a number of human papillomavirus (HPV) types; the fact that most have not yet developed a protective immune response to the virus; and their larger, more active and vulnerable cervical transformation zone.
As a result, cytologic abnormalities are very common in adolescents shortly after they become sexually active. But although lesions develop very quickly, they regress just as rapidly. Low-grade squamous intraepithelial lesions (LSIL) regress in 70% to 94% of adolescents (usually in the first 24 months), and progress in only 3% to 7%.1,2 The rate of invasive cancer in adolescents is only 0.3 for every 100,000 individuals.3
In adults, HPV disease is more likely to progress and less likely to regress. Adolescents have primarily incident infection, whereas adults have a mixture of incident and prevalent infection— and prevalent infections are more likely to be persistent infections and less likely to regress over the short term than incident infections are.
CIN 2 can be an unreliable diagnosis
Some patients with CIN 2 really have CIN 1,2 (often adolescents), whereas others have CIN 2,3 (often adults). That may be one reason CIN 2 is more likely to regress in adolescents than adults. Surprisingly, a recent study by Wright and colleagues4 found otherwise: Both the incidence and natural history of CIN 2 were similar in adults and adolescents. Moore and associates set out to validate these findings by reviewing medical records at the University of Oklahoma Health Science Center in Oklahoma City.
Details of the study
Patients were managed according to the 2001 guidelines of the American Society for Colposcopy and Cervical Pathology (ASCCP). Patients younger than 21 who had CIN 2,3 were offered conservative management or excision. Those who underwent immediate conization were compared with those who were followed at 4- to 6-month intervals:
- Of 501 patients identified in the colposcopy clinic, 146 (29%) underwent immediate conization, and 77 (53%) were found to have CIN 2.
- Of the 355 (71%) who were followed conservatively, data were available for 125 patients over a median of 18 months. Regression was reported in 56%, persistence in 35%, and progression in 14%.
- Of the 55 patients with CIN 2 who opted for conservative follow-up, data were available for 23 for a median of 18 months. Lesions persisted in 17% of this cohort and progressed in 13%. Excision of progressive or stable disease was eventually performed in 17%.
Regression more likely in adolescents
Adolescents and adults had similar rates of CIN 2 in this study, but lesions regressed at a much higher rate in adolescents. This supports the ASCCP’s conservative but cautious recommendation regarding adolescents: Observation with colposcopy and cytology at 4- to 6-month intervals for 1 year is acceptable for biopsy-confirmed CIN 2, provided colposcopy is satisfactory, endocervical sampling is negative, and the patient accepts the risk of occult disease.
Just how common is HPV among adolescents?
From studies of women attending college, it has been learned that almost 40% of those who are uninfected at the time they enter college become infected within 24 months after matriculation and almost 60% become infected within 60 months.7,8
Perhaps the most revealing finding was that 100% of the 77 patients with CIN 2 who opted for immediate loop electrical excision procedure (LEEP) underwent conization. In the group managed conservatively, the corresponding figure was 17% of 23 patients. The implication: 83% of patients undergoing immediate LEEP might have been spared conization had they been followed more conservatively.
1. Moscicki AB, Shiboski S, Broering J, et al. The natural history of human papillomavirus infection as measured by repeated DNA testing in adolescents and young women. J Pediatr. 1998;132:277-284.
2. Moscicki AB, Shiboski S, Hills NK, et al. Regression of low grade squamous intraepithelial lesions in young women. Lancet. 2004;364:1678-1683.
3. Ries LA, Eisner MP, Kosary CL. SEER cancer statistics review, 1973-1999. Bethesda, Md: National Cancer Institute; 2002.
4. Wright JD, Davila RM, Pinto KR, et al. Cervical dysplasia in adolescents. Obstet Gynecol. 2005;106:115-120.
5. Moscicki AB. Impact of HPV infection in adolescent populations. J Adolesc Health. 2005;37:S3-S9.
6. Weinstock H, Berman S, Cates W. Sexually transmitted diseases among American youth: incidence and prevalence estimates, 2000. Perspect Sex Reprod Health. 2004;36:6-10.
7. Winer RL, Lee SK, Hughes JP, Adams DE, Kiviat NB, Koutsky LA. Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol. 2003;157:218-226.
8. Richardson H, Kelsall G, Tellier P, et al. The natural history of type specific human papillomavirus infections in female university students. Cancer Epidemiol Biomarkers Prev. 2003;12:485-490.