Elsevier

Gynecologic Oncology

Volume 110, Issue 2, August 2008, Pages 179-184
Gynecologic Oncology

Human papillomavirus genotype distribution in low-grade squamous intraepithelial lesions in France and comparison with CIN2/3 and invasive cervical cancer: The EDiTH III study

https://doi.org/10.1016/j.ygyno.2008.04.012Get rights and content

Abstract

Objectives

In the present study (EDiTH III study), the genotype-specific prevalence of HPV in low-grade squamous intraepithelial lesions (LSIL) was estimated to predict the potential benefit of HPV vaccination in France. This prevalence was compared to that previously reported in France in high-grade cervical intraepithelial neoplasia (CIN2/3, EDiTH II study) and squamous cell carcinoma (SCC, EDiTH I study) to identify the genotypes preferentially associated with a progression to malignancy.

Methods

397 smears with LSIL diagnosis (Preservcyt®) were retrospectively collected in different centres in France and genotyped using the INNO-LiPA assay allowing the detection of 24 HPV genotypes.

Results

HPV was found in 98% of cases. The most prevalent genotypes in LSIL in France were HPV 66 (25%), HPV 16 (21%), HPV 53 (18%), 51 (17%) and 52 (14%). HPV 16 and/or 18 were present in 28% and HPV 6, 11, 16 and/or 18 in 33% of LSIL. The highest SCC/LSIL prevalence ratios were shown for HPV 16, 33 and 18.

Conclusions

With a 95% vaccine efficacy on CIN1 and theoretical vaccine coverage of 100%, HPV vaccination might prevent 27% (with a 16, 18 bivalent vaccine) and up to 32% (with a 6, 11, 16, 18 quadrivalent vaccine) of LSIL cases in France. In this study, LSIL related to HPV 16, 18 or 33 are at highest risk of progression to malignancy and thus could require a stringent surveillance. Conversely, anxiety and over-treatment could be avoided in women with low risk of progression.

Introduction

Genital infection with human papillomavirus (HPV) is highly prevalent in young sexually active women with 60% to 80% of sexually active U.S. adolescent girls testing positive for HPV [1], [2]. Low-grade squamous intraepithelial lesions (LSIL) appear in young women early during the natural history of HPV infection. The host immune system may clear these infections which spontaneously regress to normal cytology in 47% of cases but 20% may progress to high-grade cervical intraepithelial neoplasia (CIN2/3) within 24 months [3], some of which progressing sometimes to cervical cancer [4].

About 70,000 LSIL (1.12% of the 6 million of pap smears) are diagnosed each year in France. LSIL are most often managed by colposcopy to eventually reveal a CIN. About 70% of LSIL are histologically diagnosed as CIN1 and 50% of these CIN1 are hospitalized in France [5].

Two HPV VLP L1 vaccines are now available: an HPV 16/18 bivalent vaccine, Cervarix® for the prevention of HPV 16/18-related genital diseases and an HPV 6/11/16/18 quadrivalent vaccine, Gardasil® which not only protects against HPV 16/18-related genital diseases but also against HPV 6 and HPV 11 associated genital diseases [6]. The objective of this study was to assess the genotype-specific prevalence of HPV in smears evocative of LSIL cases to predict the potential benefit of HPV vaccination in France. Instead of analyzing CIN1, we decided to work on cytological specimens since in routine screening those lead to patient management and associated morbidity. Preventing LSIL would significantly reduce the morbidity associated with the management of these lesions, reducing patient anxiety and over-treatment [5], [7], [8].

HPV type-specific prevalence in LSIL was then compared to that we previously reported in high-grade cervical intraepithelial neoplasia (CIN2/3) [9] and squamous cell carcinoma (SCC) [10] to identify genotypes associated with a lesion at risk of progression to malignancy.

Section snippets

Sample collection and patient data

397 smears with LSIL diagnosis were obtained from three French Centres collecting smears on liquid medium: two university hospitals (Amiens and Reims, n = 197) and one private laboratory (Paris, n = 200). All cervical smears had been collected on liquid-based cytological medium (Preservcyt®). These specimens were retrospectively collected by descending chronological order starting on October 2006.

Patient data such as age at diagnosis, area of residence, and year of sample collection were extracted

Results

A total of 397 LSIL cases recruited from three different (public and private) centres in France were included in this study. Fifty percent of cases were recruited in the Paris Centre and 25% in each of the two other centres (Amiens and Reims). Median age at diagnosis was 31 years (range 16–72). HPV was present in 390/397 cases (98.2%). One hundred and ninety-two cases (48.4%) had a single infection whereas 198 (49.9%) had at least 2 HPV genotypes. Presence of at least one high-risk HPV genotype

Discussion

This study is the first large survey describing the HPV genotype-specific prevalence among LSIL cases in France. Compared with two other EDiTH studies using the same methodology, on CIN2/3 and invasive cervical cancer specimens collected between 2000 and 2005 [9], [10], our results clearly identify genotypes most likely to progress to invasive cervical lesions of increasing severity.

In these two previous studies conducted on CIN2/3 and cervical cancer [9], [10], we reported that HPV was present

Conflict of interest statement

– Jean-Luc Prétet is a consultant for Sanofi Pasteur MSD.

– Anne-Carole Jacquard is an employee of Sanofi Pasteur MSD which has developed and now distributes Gardasil HPV 6-11-16-18 vaccine.

– Maëlle Saunier: No conflict of interest.

– Christine Clavel was a speaker at a Sanofi Pasteur MSD session at the Eurogin 2007 meeting.

– Roger Dachez: No conflict of interest.

– Jean Gondry: No conflict of interest.

– Pierre Pradat: No conflict of interest.

– Benoît Soubeyrand is an employee of Sanofi Pasteur

Acknowledgments

We gratefully thank Emilie Maillard, Therapharm, Boulogne Billancourt, France, for data management and analysis, and Nubia Muñoz for critically commenting the manuscript.

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      In the low-risk HPV group, the regression rate was even higher (75%), with no cases of progression (Fig. 3). Several studies have demonstrated that the prevalence of HPV DNA in LSIL ranges from 51% to 98% (Prétet et al., 2008; Rousseau et al., 2003; Dursun et al., 2009; Cavalcanti et al., 1994; Cavalcanti et al., 2000; Zuna et al., 2006; Fernandes et al., 2009; Said et al., 2009; Schlecht et al., 2003; Spinillo et al., 2009; ASCUS-LSIL Triage Study (ALTS) Group, 2003). In our study, the HPV DNA prevalence rate in LSIL reached 87%.

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    This study was funded by Sanofi Pasteur MSD.

    1

    Etude de la Distribution des Types d'HPV en France.

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