Elsevier

The Lancet

Volume 364, Issue 9446, 6–12 November 2004, Pages 1678-1683
The Lancet

Articles
Regression of low-grade squamous intra-epithelial lesions in young women

https://doi.org/10.1016/S0140-6736(04)17354-6Get rights and content

Summary

Background

The aim of this study was to assess the probability of low-grade squamous intra-epithelial lesion (LSIL) regression in young women, and to examine the factors associated with this regression.

Methods

In a longitudinal study of human papilloma virus (HPV) infection, female adolescents aged 13–22 years were examined every 4 months by cytology, colposcopy, and HPV DNA status. Both prevalent and incident LSIL cases were included in the analysis, with regression defined as at least three consecutive normal Pap smears.

Findings

Median follow-up time from baseline (defined as the time of first LSIL diagnosis) for the 187 women with LSIL was 61 months (IQR 34–80). Median time they had been sexually active at diagnosis was 3·2 years (2·6–6·5). Probability of regression for the entire cohort was 61% (95% CI 53–70) at 12 months and 91% (84–99) at 36 months of follow-up. No associations were found between LSIL regression and HPV status at baseline, sexual behaviour, contraceptive use, substance or cigarette use, incident sexually transmitted infection, or biopsy. Multivariate analysis showed that only HPV status at the current visit was associated with rate of regression, whether infection was caused by one or more viral types (relative hazard=0·3 [95% CI 0·21–0·42], and 0·14 [0·08–0·25], respectively).

Interpretation

The high rate of regression recorded in this study lends support to observation by cytology in the management of LSIL in female adolescents. Negative HPV status was associated with regression, suggesting that HPV testing could be helpful in monitoring LSIL.

Introduction

Although human papillomavirus (HPV) infections are strongly linked to the development of cervical cancer, genital HPV infections are common in adolescent and young women, occurring in up to 70% of those who are sexually active.1 More than 70% of HPV infections are transient.1, 2, 3 A cytological manifestation of HPV, low-grade squamous intra-epithelial lesions (LSIL), is also quite common in women; about 25% of adolescent and young women develop LSIL after an HPV infection.4 Although LSIL is thought to be a benign expression of HPV infection, risk factors for of development of LSIL seem to be distinct from those associated with acquiring HPV, which suggests that LSIL development is not a simple HPV infection.4 Additionally, findings of observational studies in adult women have shown that about 20–40% of these lesions will progress to high-grade squamous intra-epithelial lesions (HSIL)—with only 50–60% spontaneously regressing.5, 6, 7

Most natural history studies of LSIL, however, have focused on women in their mid-20s to 40s who might represent a population with HPV infections that are already persistent.5, 6, 7, 8, 9, 10 We postulate that the rate of LSIL regression in adolescent and young women could be much higher than that reported for older women. The objective of this study was to define the probability of LSIL regression in adolescent and young women, and to examine the factors associated with this regression.

Section snippets

Participants

Women included in this analysis were part of a 10-year natural history study of HPV infection, which was initiated in 1990. The cohort population and study design have been described in detail elsewhere.1 In brief, women aged 13–22 years who attended one of two family planning clinics between 1990 and 1994 were screened for cervical HPV DNA with a commercial test (HPV Profile, Digene Diagnostics, Silver Spring, MD, USA). Those who tested positive and were eligible—ie, with no previous history

Results

899 women in our study of the natural history of HPV infection had valid cytology results; of these, 260 were diagnosed with LSIL by cytology at baseline or at a subsequent visit. 17 women were removed from the study because they had HSIL on histology, six left during the first year of the study because the protocol during 1990–91 called for women with histologically confirmed LSIL to be removed from the study for treatment (this protocol was amended to allow follow-up in 1991), 24 dropped out

Discussion

Our findings suggest that strategy of colposcopy for all adolescent and young women with LSIL is unwarranted and leads to unnecessary intervention, morbidity, and cost. Instead, assessment with serial cytology might be appropriate. In our study, LSIL spontaneously regressed in most women by 3 years of follow-up, showing the benign nature of this condition in adolescent and young women. This high rate of regression and low rate of progression is in accord with overall low rates of HSIL diagnosed

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