Elsevier

The Lancet

Volume 354, Issue 9172, 3 July 1999, Pages 20-25
The Lancet

Articles
Relation of human papilloma virus status to cervical lesions and consequences for cervical-cancer screening: a prospective study

https://doi.org/10.1016/S0140-6736(98)12490-XGet rights and content

Summary

Background

A relation has been established between infection with high-risk types of human papillomavirus and development of cervical cancer. We investigated a role for testing for human papillomavirus as part of cervical-cancer screening.

Methods

We monitored by cytology, colposcopy, and testing for high-risk human papillomavirus 353 women referred to gynaecologists with mild to moderate and severe dyskaryosis. The median follow-up time was 33 months. At the last visit we took biopsy samples. Our primary endpoint was clinical progression, defined as cervical intraepithelial neoplasia (CIN) 3, covering three or more cervical quadrants on colposcopy, or a cervical-smear result of suspected cervical cancer.

Findings

33 women reached clinical progression. All had persistent infection with high-risk human papillomavirus. The cumulative 6-year incidence of clinical progression among these women was 40% (95% CI 21–59). In women with end histology CIN 3, 98 (95%) of 103 had persistent infection with high-risk human papillomavirus from baseline. Among women with mild to moderate dyskaryosis at baseline, a second test for human papillomavirus at 6 months predicted end histology CIN 3 better than a second cervical smear.

Interpretation

Persistent infection with high-risk human papillomavirus is necessary for development and maintenance of CIN 3. All women with severe dyskaryosis should be referred to gynaecologists, whereas women with mild to moderate dyskaryosis should be referred only after a second positive test for high-risk human papillomavirus at 6 months.

Introduction

Cervical cancer is the second most common cancer in women worldwide, and its development through premalignant stages has been the subject of several studies.1 Nationwide screening programmes have been set up that have led to decreases in the incidence of cervical cancer.2 Important drawbacks of screening programmes, such as too many screening rounds, over-reading of slides, and overtreatment of cervical intraepithelial neoplasia (CIN), underscore the need for changes to the rationale for organised cervical-cancer screening programmes.3

Several epidemiological studies have established a strong relation between infection with high-risk types of human papillomavirus and the development of cervical cancer and its precursors.4, 5, 6, 7, 8, 9, 10, 11, 12 Insight into the relation between human papillomavirus and the natural history of CIN lesions can lead to more efficient cervical-cancer screening strategies by combining cervical smears with testing for human papillomavirus.13, 14, 15, 16

We prospectively studied the development, persistence, and progression of CIN lesions in relation to human papillomavirus status in women referred to gynaecologists because of abnormal cervical-smear results.

Section snippets

Patients

405 women referred to the colposcopy clinic of the Free University Hospital, Amsterdam, from June, 1990, to December, 1992, were eligible for the study and were willing to participate. Inclusion criteria were: an abnormal cervical smear (ie, mild to moderate or severe dyskaryosis); age 18–55 years; no medical history of cervical pathology, prenatal diethylstilboestrol exposure, or concomitant cancer; and sufficient Dutch or English language skills.

At baseline we asked women to complete a

Results

After the initial visit, 52 of 405 women were excluded because: the primary endpoint had been reached (25); the squamocolumnar junction was not visible at colposcopy (17); the classification of colposcopic impression was impossible because of erosion (five); and unintended protocol violations at baseline (a biopsy sample was taken accidentally in five). Of these 52 women, 34 (65%) had severe and 18 (35%) mild to moderate dyskaryosis. Among the women with severe dyskaryosis, histology showed two

Discussion

Clinical progression was not seen in the absence of high-risk human papillomavirus. Persistent infection with high-risk human papillomavirus is, therefore, required for development and maintenance of CIN 3.

Factors other than high-risk human papillomavirus have been reported to contribute to the development of CIN 3.8, 9, 26, 27 In our study, however, we found no additional risk factors for end histology CIN 3. Although the number of women with high-risk human papillomavirus was low, we found no

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