Natural history of cervical squamous intraepithelial lesions: a meta-analysis

doi:10.1016/S0029-7844(98)00245-2

Obstetrics & Gynecology

Volume 92, Issue 4, Part 2, October 1998, Pages 727-735

https://doi.org/10.1016/S0029-7844(98)00245-2 Get rights and content

Abstract

Objective: To define the strengths and weaknesses of existing research on the natural history of cervical squamous intraepithelial lesions (SIL) and to estimate rates of progression and regression without treatment.

Data Sources: Studies of women whose cervical smears showed squamous atypia or worse and who were observed for a minimum of 6 months were identified by a search of MEDLINE from 1966 to 1996, Current Contents, the Federal Research in Progress database, and references of review articles and identified studies, and by experts in the field.

Methods of Study Selection: Fifteen of 81 studies were eligible for data extraction. To be eligible, studies had to report a minimum of 6 months’ follow-up without treatment; relate entry cytologic findings to outcomes; and report entry cytologic findings so that the study population could be stratified into categories of atypical cells of undetermined significance (ASCUS), low-grade SIL, or high-grade SIL. Studies published before 1970 were excluded.

Tabulation, Integration, and Results: Eligible studies, representing 27,929 patients, were stratified according to entry cytologic findings. The following rates of progression to high-grade SIL at 24 months were found: ASCUS, 7.13% (95% confidence interval [CI] 0.8%, 13.5%); low-grade SIL, 20.81% (6.08%, 35.55%); and high-grade SIL, 23.37% (12.82%, 32.92%). The following rates of invasive cancer at 24 months were found: ASCUS, 0.25% (0%, 2.25%); low-grade SIL, 0.15% (0%, 0.71%); and high-grade SIL, 1.44% (0%, 3.95%). The following rates of regression to normal were found: ASCUS, 68.19% (57.51%, 78.86%); low-grade SIL, 47.39% (35.92%, 58.86%); and high-grade SIL, 35.03% (16.57%, 53.49%). Study heterogeneity was not explained by regression analysis of study level variables.

Conclusion: Our findings for borderline and low-grade abnormal cervical cytologic results suggest a relatively low risk of invasive cervical cancer with observation up to 24 months and support the clinical policy of early colposcopy for high-grade lesions.

Section snippets

Data sources

All studies in which women with cervical smears showing squamous atypia or worse were observed for a minimum of 6 months before treatment were initially eligible for inclusion. A MEDLINE search of the English language medical literature was conducted for the years 1966 to 1996, using the medical subject headings cervix neoplasms, vaginal neoplasms, vaginal smears, atypia, cervix dysplasia, cervix carcinoma, colposcopy, patient follow-up, and natural history. Searches of the Federal Research in

Study selection

After initial identification of potentially relevant studies, all studies were reviewed in detail by one of the authors (J.M. or J.N.), and additional exclusion criteria were applied. Because our inquiry focused on the natural history of cervical intraepithelial lesions (and not on the effect of current treatment), no initial limitation was placed on the age of the studies reviewed. However, after review and attempted stratification of cytologic classifications used, studies published before

Data extraction and analysis

Eligible studies were abstracted by two of the authors (J.M. and J.N.), according to a predetermined data extraction format. Key variables included entry cytology results, follow-up time, whether biopsy was performed, and outcomes, expressed as cytologic results, colposcopy findings, or pathologic results from cervical biopsy, cone biopsy, or (rarely) hysterectomy. When mean or median follow-up time for the study group was not reported directly, it was estimated as half the total follow-up time

Tabulation, integration, and results

We initially screened 301 studies for inclusion in the analysis; 229 did not report 6 months’ follow-up. Nine additional references were identified through review of references and contacts with experts, resulting in 81 total studies for review. Forty-seven reports were excluded after secondary review: 18 had unclear reporting of outcomes or inability to relate entry cytologic finding to outcome (cytology, colposcopy, or pathology); 12 did not meet the minimum requirement of 6 months’

Discussion

Although reviews on the natural history of untreated cervical dysplasia have been published previously,59, 60 ours is the first to our knowledge, based on our literature review, to apply the techniques of meta-analysis to the English language literature on this topic. Studies of women whose cervical smears showed squamous atypia or worse and who were observed for a minimum of 6 months were identified by a search of MEDLINE from 1966 to 1996, Current Contents, the Federal Research in Progress

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Three months after treatment, among 258 low-grade squamous intraepithelial lesion with high-risk HPV infection patients, total baseline HPV remission rates was 64.34 % (166/258). The remission rate of HPV16/18 group was not statistically significant compared to the HPV non-16/18 group (73.13 % vs 61.26 %, p = 0.081).The remission rates of the <50 age group was significantly higher than the >50 age group (67.28 %vs46.34 %, p = 0.001). The total lesion regression rate wa treatment, among 258 low-grade squamous intraepithelial lesion with high-risk HPV infection patients, total baseline HPV remission rates was 64.34 % (166/258). The remission rate of HPV16/18 group was not statistically significant compared to the HPV non-16/18 group (73.13 % vs 61.26 %, p = 0.081).The remission rates of the <50 age group was significantly higher than the >50 age group (67.28 %vs46.34 %, p = 0.001). The total lesion regression rate was 84.88 % (219/258). 12.8 % (33/258) of patients did not progress. Only 2.33 % (6/258) patients progressed to high-grade squamous intraepithelial lesion and accepted loop electrosurgical excision procedure. The patients >50 age group had significant higher progression rate than the patients ＜50 age group (p＜0.05). Six months after treatment, except for 6 patients who progressed to high-grade squamous intraepithelial lesion and underwent surgical treatment, the total baseline HPV remission rates was up to 82.54 % (208/252).
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View all citing articles on Scopus

^☆: This study was funded by grant R01-CA70104-0 from the National Cancer Institute.

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ReviewsNatural history of cervical squamous intraepithelial lesions: a meta-analysis☆

Abstract

Section snippets

Data sources

Study selection

Data extraction and analysis

Tabulation, integration, and results

Discussion

Gynecol Oncol

Lancet

Obstet Gynecol Clin North Am

Am J Obstet Gynecol

Lancet

Lancet

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Lancet

Lancet

Arch Phys Med Rehabil

Controlled Clin Trials

J Clin Epidemiol

Screening for cervical cancer

The Papanicolaou test for cervical cancer detection. A triumph and a tragedy

JAMA

Healthy people 2000 at mid decade

JAMA

Prevalence of dysplasia and cancer of the cervix in a nationwide, planned parenthood population

Cancer

Results from the National Breast and Cervical Cancer Early Detection Program, October 31, 1991–September 30, 1993

MMWR Morbid Mortal Wkly Rep

Interim guidelines for management of abnormal cervical cytology. The 1992 National Cancer Institute Workshop

JAMA

Report of a national workshop on screening for cancer of the cervix

Can Med Assoc J

Cervical cytology: evaluation and management of abnormalities. ACOG technical bulletin no. 183

Management choices for patients with “squamous atypia” on Papanicolaou smear. A toss up?

Med Care

Mild cervical cytological abnormalities

BMJ

Controversies in the management of low-grade cervical intraepithelial neoplasia

Cancer

Comparative utility of repeat Papanicolaou smears, cervicography, and colposcopy in the evaluation of atypical Papanicolaou smears

Obstet Gynecol

Every woman with an abnormal cervical smear should be referred for treatmentdebate

Clin Obstet Gynecol

Management of initial atypical cervical cytologya randomized, prospective study

Obstet Gynecol

Long term follow up of women with borderline cervical smear test resultseffects of age and viral infection on progression to high grade dyskaryosis

BMJ

Reviews
Natural history of cervical squamous intraepithelial lesions: a meta-analysis☆