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☆
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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2016, Journal de Gynecologie Obstetrique et Biologie de la ReproductionThe association of HPV genotype with the regression, persistence or progression of low-grade squamous intraepithelial lesions
2015, Experimental and Molecular PathologyCitation Excerpt :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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