Elsevier

Gynecologic Oncology

Volume 90, Issue 3, September 2003, Pages 587-592
Gynecologic Oncology

Regular article
Value of human papillomavirus testing after conization by loop electrosurgical excision for high-grade squamous intraepithelial lesions

https://doi.org/10.1016/S0090-8258(03)00372-XGet rights and content

Abstract

Objective

The aim of the study was to evaluate human papillomavirus (HPV) testing during the follow-up of patients after conization by loop electrosurgical excision for high-grade squamous intraepithelial lesion.

Methods

A prospective study was conducted on 205 patients who underwent conization for high-grade squamous intraepithelial lesion (CIN 2 or 3). Loop electrosurgical excision procedure (LEEP) was used in all cases. High-risk HPV testing was realized by the Hybrid Capture II system before and 3 months after conization.

Results

Of the 205 patients, 193 (94.1%) were positive for the HPV test before conization. Seventy-one were HPV positive after conization (34.6%). The margins were positive in 36.1%. Residual disease was observed in 27 cases (13.2%). Four patients (2%) developed a recurrence after a mean follow-up of 18.1 months (+/−12). There was no correlation between pretreatment HPV testing and the residual disease or recurrence. Patients with positive margins were significantly more likely to have residual disease than those with negative margins (P < 0.0001). Residual disease was more likely to occur when the posttreatment HPV test was positive (P < 10−7). All recurrences were observed in patients with a positive posttreatment HPV test (P < 0.05). Residual disease and recurrence were correctly predicted with a sensitivity of 81 and 100%, respectively, and a negative predictive value of 96 and 100%.

Conclusion

Posttreatment HPV testing could be useful in the follow-up of patients after conization. In case of negative posttreatment HPV testing, the frequency of follow-up could be reduced, particularly in those patients with free margins.

Introduction

Despite numerous cervical screening programmes worldwide, cervical neoplasia remains the second most common cause of cancer deaths in women. It is preventable by early identification and treatment of cervical intraepithelial neoplasia (CIN).

Conservative treatment, conization, is recommended for most high-grade CIN (CIN 2 and 3) [1]. A loop electrosurgical excision procedure (LEEP) is one of the most frequent treatments [2], [3]. With the major advantage that a histopathological diagnosis can be obtained, the major concern in conservative treatment is to verify whether conization removed the CIN lesion entirely. Incomplete excision is associated with an increased risk of residual disease. Seven to 85% of patients with positive margins later present with residual disease, recurrence, or invasive disease [4], [5]. However, even when the margins are free, recurrences may occur. Five to 35% of conservatively treated patients will present with recurrence [5], [6], [7]. Thus, the status of the margins is not specific enough to predict which women will develop a recurrence.

A method that could predict which women are at risk for CIN recurrence after treatment would be of great clinical importance.

The role of human papillomavirus (HPV) infection in the pathogenesis of cervical cancer is well established [1], [8]. HPV DNA testing has been proposed in the management of patients with ASCUS. Despite encouraging results from retrospective and prospective studies, HPV testing is not recommended currently in the follow-up of patients after conization.

The aim of this prospective study was to investigate whether pre- or postconization HPV testing can predict residual disease and/or recurrence of patients treated by LEEP for high-grade CIN.

Section snippets

Material and methods

Between January 1997 and April 2001, 977 women were referred to the colposcopic clinic of the University Hospital of Lille, France, for investigation of cervical abnormal cytology. Cells for HPV DNA analysis were collected from the endocervix and the transformation zone with a sterile conical brush (Cervical Sampler, Digene), prior to colposcopy. Biopsies were taken from the most abnormal area of the cervix. The cervical biopsies were assessed according to the CIN classification system as mild

Statistical analysis

Statistical analysis was carried out with the χ2 or Fisher exact tests as appropriate. The correlation between HPV status and residual or recurrent lesions after conization was studied. A P value of <0.05 was taken to be statistically significant. The confidence intervals (95%) of the odds ratio have been calculated according to Cornfield.

Sensitivity, specificity, false-positive rate, false-negative rate, positive predictive value, and negative predictive value were calculated with regard to

Descriptive results

A total of 205 patients were included in this prospective study performed between January 1997 and April 2001. The age range was 17 to 69 (34.7 +/−9.17).

The HPV test was positive before treatment in 94.1% (n = 193). Three months after the conization, 71 patients were HPV positive (34.6%). Three of them were HPV negative before the conization.

All the patients had LEEP. Pathologic examination of the excised cervical specimen showed positive margins in 74 patients (36.1%). Exocervical margins were

Discussion

Numerous studies have shown that there is a highly significant association between persistent infection with high-risk HPV and high-grade lesions [9], [10]. In our study, 94% of the patients presenting with high-grade lesions had high-risk HPV prior to treatment in accordance with the literature [7], [11], [12], [13], [14], [15], [16], [17]. The HPV testing was made on a fresh sample. In some retrospective studies, the HPV testing was performed on formalin-fixed tissues and it is possible that

Conclusion

Pretreatment HPV testing is unable to predict the quality of loop excision, the risk of persistence, or recurrence of the disease.

Posttreatment HPV testing, with its good negative predictive value, should be useful to monitor patients after loop excision. When the posttreatment HPV test is negative, particularly if the margins are free, follow-up could be reduced.

Patients with persistent HPV infection after conization for high-grade SIL should be regularly investigated because they are at risk

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