Human Papillomavirus Types Distribution in Organised Cervical Cancer Screening in France

International audienceBackground: Knowledge of prevalence rates and distribution of human papillomavirus (HPV) genotypes prior high HPV vaccine coverage is necessary to assess its expected impact on HPV ecology and on cervical lesions and cancers.Methods: Residual specimens of cervical cytology (N = 6,538) were obtained from 16 sites participating in organised cervical cancer screening pilot programs throughout France, anonymised and tested for HPV DNA using the PapilloCheck® genotyping test. Samples were stratified according to age of women and cytological grades.Results: The age-standardised prevalence rates of HPV 16 and/or 18 (with or without other high-risk types) was 47.2% (95% Confidence Interval, CI: 42.4–52.1) in high-grade squamous intraepithelial lesions (HSILs), 20.2% in low-grade SIL (95% CI: 16.7–23.7) and 3.9% (95% CI: 2.8–5.1) in normal cytology. Overall HR HPV were detected in 13.7% (95%I CI: 11.7–15.6) of normal cytology. In women below 30 years of age, 64% of HSILs were associated with HPV16 and/or 18. In our study population, HPV16 was the most commonly detected type in all cervical grades with prevalence rates ranking from 3.0% in normal cytology to 50.9% in HSILs. HPV16 was also detected in 54% (27/50) of invasive cervical cancers including 5 adenocarcinomas.Conclusion: HPV16 was strongly associated with cervical precancer and cancer. The high prevalence rates of HPV16/18 infection among women below 30 years of age with HSILs suggests that the impact of vaccination would be primarily observed among young women

Sample Submission and Human Papilloma Virus (HPV) Testing Algorithm for Residual Liquid Based Cytology (LBC) Samples.

<p>Sample Submission and Human Papilloma Virus (HPV) Testing Algorithm for Residual Liquid Based Cytology (LBC) Samples.</p

Age specific prevalence of HPV infection in different cytology groups.

<p>Prevalence of HPV infection High Risk (HR) but not 16 and/or 18 and HPV16 and/or 18 without or with another HPV type by cervical grade and age group. ASC-US, Atypical Squamous Cells of Undetermined Significance; LSIL, Low Grade Squamous Intra-epithelial Lesion; HSIL, High Grade Squamous Intra-epithelial Lesion.</p

Geographic location of participants and cytology grade of samples.

<p>HR HPV, High Risk HPV; ASC-US, Atypical Squamous Cells of Undetermined significance; LSIL, Low grade Squamous Intra-epithelial Lesion; HSIL, High grade Squamous Intra-epithelial Lesion.</p

Age standardized infection rate by cytology grade.

<p>HR HPV, High Risk HPV; ASC-US, Atypical Squamous Cells of Undetermined Significance; LSIL, Low grade Squamous Intra-epithelial Lesion; HSIL, High grade Squamous Intra-epithelial Lesion; CI, Confidence Interval.</p

Prevalence of HR HPV by age group among the 5326 women eligible for routine screening (age 25–65).

<p>HR HPV, High Risk HPV; CI, Confidence Interval.</p

Human papillomavirus types by cytology grades (n = 6139).

<p>HPV types were detected with the PapilloCheck® technique. N+: Number of positive samples. ASC-US, Atypical Squamous Cells of Undetermined Significance; LSIL, Low grade Squamous Intra-epithelial Lesion; HSIL, High grade Squamous Intra-epithelial Lesion; tot, total.</p

Broad-Range Papillomavirus Transcriptome as a Biomarker of Papillomavirus-Associated Cervical High-Grade Cytology

International audienceHuman Papillomaviruses (HPV) are responsible for over 99% of cervical cancers. Molecular diagnostic tests based on the detection of viral DNA or RNA have low Positive Predictive Values (PPV) for the identification of cancer or precancerous lesions. Triage with the Papanicolaou test lacks sensitivity and even when combined with molecular detection of high-risk HPV results in a significant number of unnecessary colposcopies. We have developed a broad range detection test of HPV transcripts to take a snapshot of the transcriptome of 16 high-risk or putative high-risk HPV in cervical lesions (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73, and 82). The purpose of this novel molecular assay is to detect and type HPV-positive samples and to determine a combination of HPV reads at certain specific viral spliced junctions that can better correlate with high-grade cytology, reflecting the presence of precancerous cells. In a proof-of-concept study conducted on 55 patients, starting from cervical smears, we have shown that (i) HPV RNA-Seq can detect papillomaviruses with performances comparable to a widely used HPV reference molecular diagnostic kit, and (ii) a combination of the number of sequencing reads at specific early vs late HPV transcripts can be used as a marker of high-grade cytology, with encouraging diagnostic performances as a triage test

Investigation of viral etiology in potentially malignant disorders and oral squamous cell carcinomas in non-smoking, non-drinking patients

International audienceHead and neck squamous cell carcinomas (HNSCC) are the seventh most frequent cancers. Among HNSCCs, oral squamous cell carcinomas (OSCCs) include several anatomical locations of the oral cavity, but exclude the oropharynx. The known risk factors for OSCCs are mainly alcohol consumption and tobacco use for at least 75-80% of cases. In addition to these risk factors, Human papillomavirus (HPV) types 16 and 18, classified as high-risk (HR) HPV genotypes, are considered as risk factors for oropharyngeal cancers, but their role in the development of OSCC remains unclear. We tested the hypothesis of viral etiology in a series of 68 well-characterized OSCCs and 14 potentially malignant disorders (PMD) in non-smoking, non-drinking (NSND) patients using broad-range, sensitive molecular methodologies. Deep-sequencing of the transcriptome did not reveal any vertebrate virus sequences other than HPV transcripts, detected in only one case. In contrast, HPV DNA was detected in 41.2% (28/68) and 35.7% (5/14) of OSCC and PMD cases, respectively. Importantly, 90.9% (30/33) of these belonged to the Betapapillomavirus genus, but no viral transcripts were detected. Finally, high-throughput sequencing revealed reads corresponding to transcripts of the Trichomonas vaginalis virus (TVV), which were confirmed by RT-PCR in two OSCCs. Our results strongly suggest that Alphapapillomavirus genotypes classified as HR are not involved in the development of OSCCs in NSND patients and that known oncogenic infectious agents are absent in these specific OSCCs. Any possible direct or indirect role of Betapapillomavirus genus members and TVV in OSCCs remains speculative and requires further investigation

Immunogenicity of a Plasmodium vivax vaccine based on the duffy binding protein formulated using adjuvants compatible for use in humans

Abstract The invasion of reticulocytes by Plasmodium vivax merozoites is dependent on the interaction of the Plasmodium vivax Duffy Binding Protein (PvDBP) with the Duffy antigen receptor for chemokines (DARC). The N-terminal cysteine-rich region II of PvDBP (PvDBPII), which binds DARC, is a leading P. vivax malaria vaccine candidate. Here, we have evaluated the immunogenicity of recombinant PvDBPII formulated with the adjuvants Matrix-M and GLA-SE in mice. Analysis of the antibody responses revealed comparable ELISA recognition titres as well as similar recognition of native PvDBP in P. vivax schizonts by immunofluorescence assay. Moreover, antibodies elicited by the two adjuvant formulations had similar functional properties such as avidity, isotype profile and inhibition of PvDBPII-DARC binding. Furthermore, the anti-PvDBPII antibodies were able to block the interaction of DARC with the homologous PvDBPII SalI allele as well as the heterologous PvDBPII PvW1 allele from a Thai clinical isolate that is used for controlled human malaria infections (CHMI). The cross-reactivity of these antibodies with PvW1 suggest that immunization with the PvDBPII SalI strain should neutralize reticulocyte invasion by the challenge P. vivax strain PvW1