Yann Leocmach

Human Papillomavirus Genotype Distribution in External Acuminata Condylomata: A Large French National Study (EDiTH IV)

BACKGROUND External acuminata condylomata (EAC) are among the most common sexually transmitted diseases. Although it is understood that low-risk human papillomavirus (HPV) genotypes 6 and 11 are associated with EAC, there have only been a few, small, published studies reporting the genotype-specific prevalence of HPV. The objective of our study was to assess the prevalence of HPV genotypes for a large number of cases involving both men and women and to evaluate the potential benefit of a quadrivalent (genotypes 6, 11, 16, and 18) HPV vaccine in France. METHODS A total of 256 women and 260 men who presented with EAC to French gynecologists, dermatologists, and proctologists were prospectively recruited during the period January through April 2007. Specimens were collected with a cytobrush, and the HPV genotype was determined using the INNO-LiPA assay (Innogenetics), which detects 24 HPV genotypes. RESULTS Four hundred twenty-three beta-globin-positive samples could be analyzed. The median age of patients was 30 years (range, 18-72 years). The overall prevalence of HPV DNA in patients with EAC was 99% (33% of patients were coinfected with another pathogen). Low-risk genotypes predominated, with a prevalence of 89%. The most prevalent genotypes were 6 (69%) and 11 (16%), followed by 16 (9%), 51 (8%), 52 (7%), 66 (6%) 53 (5%), 31 (3%), and 18 (3%). The cumulative prevalence of genotypes 6 and 11 was 83%, and the cumulative prevalence of genotypes 6, 11, 16, and 18 was 88%. CONCLUSIONS This study is, to our knowledge, the first large, multicenter survey to provide solid data on HPV genotype distribution among patients with EAC. Our results provide strong evidence that, in France, the most prevalent HPV genotypes in persons with EAC are 6 and 11. Because of its 99% efficacy for the prevention of EAC and a vaccine coverage of 100%, the quadrivalent HPV vaccine could prevent 62%-87% of EAC cases in France.

Human papillomavirus genotype distribution in anal cancer in France: the EDiTH V study.

Anal cancer is a rare cancer but its incidence is increasing. Human papillomavirus (HPV) infection seems to be associated with the occurrence of most cases. The genotype‐specific prevalence of HPV in anal cancer was estimated to assess the potential benefit of HPV vaccination in France. Anal cancer histological specimens were retrospectively recruited in 2008 from 16 French centres and centrally tested for HPV genotyping using the INNO‐LiPA assay allowing the detection of 28 genotypes. Results were analyzed according to age, gender, HIV status when available and histological diagnosis. A total of 366 anal cancer cases were analyzed among which 62% were females. Mean age at diagnosis was 54.8 years in males and 66.4 years in females (p < 0.001). HPV was found in 96.7% of cases, 72% being infected by a single HPV type. Presence of at least one high‐risk genotype was observed in 91% of cases (96% in females and 83% in males; p < 0.001). HPV16 was by far the most prevalent genotype (75%), followed by HPV18, HPV52, HPV33, and HPV51 (4–6%). HPV16/18 alone or in association were found in 78% of all cases. HIV‐positive cases had a higher proportion of multiple HPV infection than HIV‐negative cases and a slightly different HPV type distribution with an under‐representation of HPV16 and an over‐representation of other types. Our results indicate that anal cancer rarely occurs in the absence of HPV and emphasize the predominant role of HPV16. The potential benefit of HPV vaccine on the occurrence of anal cancer should be further evaluated.

Human papillomavirus genotype distribution in oropharynx and oral cavity cancer in France—The EDiTH VI study

BACKGROUND The incidence of oropharyngeal cancers has gradually increased over the last decades. Recent studies suggest an association between human papillomavirus (HPV) infection and several head and neck cancers, especially oropharyngeal and oral cavity invasive carcinomas. OBJECTIVES The objective was to assess the overall and type specific HPV prevalence in oropharyngeal and oral cavity carcinomas in France. STUDY DESIGN Paraffin-embedded tumour specimens were retrospectively collected in 12 French centres and centrally tested for HPV detection and genotyping (INNO-LiPA assay). RESULTS A total of 523 cases (77% males) were collected, among which 60% were oropharyngeal and 40% oral cavity carcinomas. The most frequent anatomical sites were tonsil (58.9%) and base of tongue (13.7%) for the oropharynx and floor of mouth (41.1%) and oral tongue (38.3%) for the oral cavity. Overall HPV prevalence was 46.5% in oropharyngeal carcinomas and 10.5% in oral cavity carcinomas and was higher in female than in male cases (63.5% vs 42.2% in oropharynx and 17.2% vs 8.0% in oral cavity). About 95% of HPV-positive cases were infected by a single HPV type. HPV 16 was the most prevalent type and was found in 89.7% and 95.5% of HPV-positive oropharyngeal and oral cavity carcinoma cases, respectively. All other HPV types had prevalence below 5%. CONCLUSIONS Our results indicate that HPV is common among oropharyngeal and oral cavity carcinoma cases in France and emphasize the predominance of HPV 16. The potential benefit of HPV vaccination on the occurrence of head and neck carcinomas should be further evaluated.

Human papillomavirus (HPV) genotype distribution in invasive cervical cancers in France: EDITH study

Invasive cervical cancer (ICC) remains a significant cause of morbidity and mortality in France. Since human papillomavirus (HPV) is the necessary cause of ICC, the aim of this study was to assess the type‐specific prevalence of HPV in ICC in France in order to locally evaluate the potential benefit of an HPV 16/18 L1 virus‐like particles (VLP) vaccination. A total of 516 histological specimens collected in 15 centers were analyzed. Among them, 86% had a diagnosis of squamous cell carcinoma (SCC) whereas 14% were adenocarcinomas (ADC). HPV genotyping was performed using the INNO‐LiPA assay allowing the specific detection of 24 HPV genotypes both high risk (HR) and low risk (LR). The overall HPV prevalence in ICC was 97%. The most prevalent genotypes were HPV 16 (73%) and HPV 18 (19%) followed by HPV 31 (7%), 33, 68, 45, 52 and 58 (4.1–2.3%). HPV 16 and/or 18 were associated with 82% of ICC, 10% being HPV 16 and 18 coinfections. While HPV 16 was the most prevalent type in both SCC (74%) and ADC (64%), HPV 18 was by far more prevalent in ADC (37%) compared to SCC (16%; p < 0.001). Multiple infections with at least two different HR HPV genotypes were observed in 22% of ICC. Given the high HPV 16/18 prevalence and taking into account possible production of crossneutralizing antibodies against other HPV types, HPV 16/18 L1 VLP vaccination would be expected to significantly reduce the burden of ICC in France.

Human papillomavirus genotype distribution in high grade cervical lesions (CIN 2/3) in France: EDITH study.

High grade cervical intraepithelial neoplasia (CIN 2/3) have a high potential to progress to invasive cervical cancer (ICC). Pap testing including follow‐up and treatment of CIN 2/3 is currently the best prevention of ICC, but is associated with morbidity, namely obstetrical adverse effects and psychological distress. Human papillomavirus (HPV) is universally accepted as the necessary cause of ICC. The objective of the present study was to describe the type‐specific prevalence of HPV in CIN 2/3 in France and hereby to locally estimate the potential benefit of an HPV 16/18 L1 virus‐like particles (VLP) vaccine. A total of 493 formalin‐fixed and paraffin‐embedded CIN 2/3 specimens were analyzed. Medical records were examined for patient related data. HPV were genotyped with the INNO‐LiPA assay allowing the detection of 24 HPV genotypes. The overall prevalence of LiPA detectable HPV was 98%. The most prevalent genotype was HPV 16 (62%) followed by HPV 31 (15%), 33 (12%), 52 (9%), 51 (8%), 58 (7%), 35 and 18 (4%). Multiple infection with at least two different high‐risk (HR) HPV genotypes was observed in 26% of all specimens including 2.6% with HPV 16 and 18 multiple infections. The present study indicates that HPV 16 is by far the most common HPV type associated with CIN 2/3 in France. With an HPV 16 and 18 prevalence of 64%, HPV 16/18 L1 VLP vaccines would be expected to significantly reduce the burden associated with the management and treatment of CIN 2/3 in France.

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

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.

French women’s knowledge of and attitudes towards cervical cancer prevention and the acceptability of HPV vaccination among those with 14 – 18 year old daughters: a quantitative-qualitative study

BackgroundIn France, it is recommended that girls and women aged 14–23 are vaccinated against the human papillomavirus (HPV). However, French women’s knowledge of and attitude towards the vaccine has been little studied.MethodsThirty-nine general practitioners, representative of those working in the large Rhône-Alpes region, offered a self-administered questionnaire on cervical cancer (CC) prevention to all 18–65 year-old women who came for consultation during June and July 2008. In addition, semi-structured interviews were undertaken with a sample of those who had daughters aged 14–18.ResultsOf the 1,478 women who completed the questionnaire, only 16.9% mentioned HPV as the cause of CC, even though 76.2% knew of the vaccine. 210 women had daughters aged 14–18, and 32 were interviewed. Compared with the wider group, more of these women were aware of the HPV vaccine (91.4%). 44.8% knew the target population and 17.1% the recommended ages for vaccination. 54.3% favoured HPV vaccination; 37.2% were undecided and only 0.9% were opposed. The main barrier to acceptance was the recency of the vaccine’s introduction and concern about possible side effects (54.9%); 14.1% preferred to rely on their GP’s decision. Factors associated with acceptance of the HPV vaccine were having previously vaccinated a child against pneumococcus (OR=3.28 [1.32-8.11]) and knowing the target population for HPV vaccination (OR=2.12 [1.15-3.90]). Knowing the recommended frequency of Papanicolaou smear testing (Pap test) screening was associated with lower acceptance (OR=0.32 [0.13-0.82]).ConclusionsFew mothers are opposed to HPV vaccination. Factors associated with acceptability were knowledge about the vaccine, acceptance of other vaccines and, unexpectedly, lack of knowledge about the recommended frequency of Pap testing. On multivariate analysis, compliance with recommendations for Pap test screening and socioeconomic factors had no effect on views about HPV vaccination. Given that concern about possible side effects is the major barrier to wider acceptance of the HPV vaccine in France, GPs have a key role in providing information.

Human papillomavirus genotype distribution in tonsil cancers.

BackgroundThe incidence of tonsil cancers has increased in several countries. French data on HPV prevalence in tonsil cancers are scarce. The objective of this study was thus to assess the overall and type specific HPV prevalence in tonsil histological samples.MethodsThis French retrospective multicenter study involved 12 centres located throughout the country. Were included 185 histological samples collected from year 2000 to 2009 with a validated diagnosis of tonsil invasive carcinomas. HPV prevalence was studied according to gender, age and histological type of cancer.ResultsOverall HPV prevalence was 57% in tonsil cancers. Mean age of diagnosis was comparable in HPV positive tonsils cases (60 ± 11.2) and HPV negative tonsil cases (59 ± 9.6). HPV prevalence was significantly higher in female than in male cases (28/35 versus 78/150 in tonsil cases, respectively, P = 0.003). About 53% of tonsil cases were infected by a single HPV type. Only eight (4%) samples were infected by more than one HPV type. Among HPV positive samples, HPV 16 was found in 89% of tonsil cases. All other HPV types had prevalence below 5%.ConclusionsOur results indicate that HPV is common in tonsil carcinomas and emphasize the predominant role of HPV 16.

Disparities of perceptions and practices related to cervical cancer prevention and the acceptability of HPV vaccination according to educational level in a French cross-sectional survey of 18-65 years old women.

Introduction We aimed to study the relationships between educational level, womens knowledge about cervical cancer (CC), and acceptance of HPV vaccination for their daughters. Methods We analysed data from a quantitative (self-administrated questionnaire) and qualitative (semi-structured interviews) cross-sectional study performed in 2008 among 1,229 French 18–65-year-old women recruited by general practitioners. Women were categorized into three educational level groups: low (LEL: 43.9%), medium (MEL: 33.4%) and high (HEL: 22.6%). Results Knowledge about CC and its prevention was lower among LEL women. In the 180 mothers of 14–18-year-old daughters (99 LEL, 54 MEL, 45 HEL), acceptance of HPV vaccine was higher in LEL (60.4%) and MEL (68.6%) than in HEL mothers (46.8%). Among LEL mothers, those who were favourable to HPV vaccination were more likely to be young (OR = 8.44 [2.10–34.00]), to be vaccinated against hepatitis B (OR = 4.59 [1.14–18.52]), to have vaccinated their children against pneumococcus (OR = 3.52 [0.99–12.48]) and to present a history of abnormal Pap smear (OR = 6.71 [0.70–64.01]). Conclusion Although LEL women had poorer knowledge about CC and its prevention, they were more likely to accept HPV vaccination than HEL mothers.

HPV vaccination among French girls and women aged 14-23 years and the relationship with their mothers' uptake of Pap smear screening: a study in general practice.

INTRODUCTION HPV vaccination is recommended in France for girls aged 14 and for those aged 15-23 before sexual debut or who have become sexually active within the previous year. The first aim was to describe vaccination practice among 14-23-year-old girls visiting a general practitioner. A second objective was to investigate factors associated with starting vaccination among girls aged 14-18, in particular the regular practice of Pap-smear screening (PSS) by their mothers. METHODS A cross-sectional study was conducted from June to August 2009. A total of 87 general practitioners from the large Rhône-Alpes region contributed data on 502 girls/women who came for consultation. RESULTS 231 (46.0%) of these girls/women had begun the process of HPV vaccination (68.2%, 56.9% and 18.7% of the 14-16, 17-20 and 21-23-year-olds respectively) of whom 139 (60.2%) had received all three doses. 92 girls/women (39.8%) had received only one or two doses at the time of study. However, in 71 (77.2%) cases, the gap between the last dose received and the time of study was within the between-dose interval recommended in the vaccination schedule. GPs reported that 16 (11.5%) had mentioned side effects following injections. Having a mother who practised regular PSS (Odds Ratio 6.2 [1.5-25.8]), having never lived with a partner (4.6 [1.6-13.5]) and vaccination against hepatitis B (3.2 [1.6-6.1]) were found to be independently correlated with the initiation of HPV vaccination among girls/women aged 14-18 years. CONCLUSION Two years after the start of the programme, only half of girls/women aged 14-23 years had begun the process of HPV vaccination. HPV vaccination status was correlated with PSS in the mother, family status and hepatitis B vaccination. Such information may help to better target girls who are less likely to be vaccinated.