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      Predictors of abnormal cytology among HPV-infected women in remote territories of French Guiana

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          Abstract

          Background

          Cervical cancer prevention using cervical cytology is insufficiently sensitive, a significant proportion of HPV-infected women having normal cytology.

          The objective of the present study was to try to identify factors associated with abnormal cytology in HPV-infected women living in remote areas of French Guiana.

          Methods

          A study was conducted in women aged 20–65 years having HPV infections confirmed by HPV DNA detection using the GREINER-BIO-ONE kit. In addition to HPV testing, cytology was performed and classified as normal or abnormal. Demographic and life history variables, and infecting genotypes were compared between the normal and abnormal cytology groups.

          Results

          None of the demographic and life history variables were associated with cytology results. HPV genotype 53 was significantly associated with absence of cytological abnormalities whereas HPV 52, 58, 16 and perhaps 33 and 66 were independently associated with a greater risk of cytological abnormalities. When grouping HPV genotypes in different species, only species 9 (HPV 16, 31, 33, 35, 52, 58, 67) was significantly associated with abnormal cytology AOR = 5.1 (95% CI = 2.3–11.2), P < 0.001.

          Conclusions

          It was not possible to predict which HPV-infected women will have cytological abnormalities or notfrom anamnesis. In this study HPV 53 seemed more benign than other HPV genotypes. On the contrary, species n°9, containing 5 of the genotypes contained in the nonavalent HPV vaccine, was significantly associated with more cytological abnormalities. HPV testing and vaccination with the nonavalent vaccine should be implemented in these remote parts of French Guiana.

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          Most cited references15

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          HPV screening for cervical cancer in rural India.

          In October 1999, we began to measure the effect of a single round of screening by testing for human papillomavirus (HPV), cytologic testing, or visual inspection of the cervix with acetic acid (VIA) on the incidence of cervical cancer and the associated rates of death in the Osmanabad district in India. In this cluster-randomized trial, 52 clusters of villages, with a total of 131,746 healthy women between the ages of 30 and 59 years, were randomly assigned to four groups of 13 clusters each. The groups were randomly assigned to undergo screening by HPV testing (34,126 women), cytologic testing (32,058), or VIA (34,074) or to receive standard care (31,488, control group). Women who had positive results on screening underwent colposcopy and directed biopsies, and those with cervical precancerous lesions or cancer received appropriate treatment. In the HPV-testing group, cervical cancer was diagnosed in 127 subjects (of whom 39 had stage II or higher), as compared with 118 subjects (of whom 82 had advanced disease) in the control group (hazard ratio for the detection of advanced cancer in the HPV-testing group, 0.47; 95% confidence interval [CI], 0.32 to 0.69). There were 34 deaths from cancer in the HPV-testing group, as compared with 64 in the control group (hazard ratio, 0.52; 95% CI, 0.33 to 0.83). No significant reductions in the numbers of advanced cancers or deaths were observed in the cytologic-testing group or in the VIA group, as compared with the control group. Mild adverse events were reported in 0.1% of screened women. In a low-resource setting, a single round of HPV testing was associated with a significant reduction in the numbers of advanced cervical cancers and deaths from cervical cancer. 2009 Massachusetts Medical Society
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            Epidemiology of HPV infection among Mexican women with normal cervical cytology.

            Cervical cancer is caused by human papillomavirus (HPV) and is the most common cancer among Mexican women, but no population-based studies have reported the prevalence and determinants of HPV infection in Mexico. A population-based study was carried out between 1996 and 1999, based on an age-stratified random sample of 1,340 women with normal cytologic diagnoses from 33 municipalities of Morelos State, Mexico. The prevalence of cervical HPV DNA was determined by reverse line blot strip assay to detect 17 cancer-associated and 10 non-cancer-associated HPV types. Two peaks of HPV DNA prevalence were observed. A first peak of 16.7% was observed in the age group under 25 years. HPV DNA prevalence declined to 3.7% in the age group 35-44 years, then increased progressively to 23% among women 65 years and older. Cancer-associated HPV types were the most common in all age groups; non-cancer-associated HPV types were rare in the young and became more common linearly with age. Twenty-four types of HPV were detected; HPV 16, HPV 53, HPV 31 and HPV 18 were the most common, but none was present in more than 1.7% of subjects. The main determinant of infection with both cancer-associated and non-cancer-associated HPV types was the number of sexual partners in all age groups. Less-educated women were at an increased risk of infection with cancer-associated but not with non-cancer-associated HPV types; low socioeconomic status was associated with detection of non-cancer-associated HPV types. Among young women an increasing number of pregnancies was associated with lower HPV detection and among older women low socioeconomic status was related to increased HPV detection, particularly for the age group 35-54 years. Among women with cancer-associated HPV types, there was a higher intensity of polymerase chain reaction signal in younger than in older age groups (p < 0.001). We present additional evidence for the sexually transmitted nature of HPV infection, regardless of age group and HPV type. We confirm previous findings of a second peak of high-risk HPV infections in postmenopausal women, in this case with a clear predominance of cancer-associated HPV types. In populations with this pattern, which can be related to reactivation of latent HPV infections or high previous exposure in older women, screening with HPV testing can have a reduced specificity among older women if proper cut-off points for HPV positivity are not used. Longitudinal studies of immune responses to HPV infection in different age groups are warranted.
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              Deep sequencing of HPV E6/E7 genes reveals loss of genotypic diversity and gain of clonal dominance in high-grade intraepithelial lesions of the cervix

              Background Human papillomavirus (HPV) is the carcinogen of almost all invasive cervical cancer and a major cause of oral and other anogenital malignancies. HPV genotyping by dideoxy (Sanger) sequencing is currently the reference method of choice for clinical diagnostics. However, for samples with multiple HPV infections, genotype identification is singular and occasionally imprecise or indeterminable due to overlapping chromatograms. Our aim was to explore and compare HPV metagenomes in abnormal cervical cytology by deep sequencing for correlation with disease states. Results Low- and high-grade intraepithelial lesion (LSIL and HSIL) cytology samples were DNA extracted for PCR-amplification of the HPV E6/E7 genes. HPV+ samples were sequenced by dideoxy and deep methods. Deep sequencing revealed ~60% of all samples (n = 72) were multi-HPV infected. Among LSIL samples (n = 43), 27 different genotypes were found. The 3 dominant (most abundant) genotypes were: HPV-39, 11/43 (26%); -16, 9/43 (21%); and -35, 4/43 (9%). Among HSIL (n = 29), 17 HPV genotypes were identified; the 3 dominant genotypes were: HPV-16, 21/29 (72%); -35, 4/29 (14%); and -39, 3/29 (10%). Phylogenetically, type-specific E6/E7 genetic distances correlated with carcinogenic potential. Species diversity analysis between LSIL and HSIL revealed loss of HPV diversity and domination by HPV-16 in HSIL samples. Conclusions Deep sequencing resolves HPV genotype composition within multi-infected cervical cytology. Biodiversity analysis reveals loss of diversity and gain of dominance by carcinogenic genotypes in high-grade cytology. Metagenomic profiles may therefore serve as a biomarker of disease severity and a population surveillance tool for emerging genotypes. Electronic supplementary material The online version of this article (doi:10.1186/s12864-017-3612-y) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                antoine.adenis@ch-cayenne.fr
                valentin.dufit@ch-cayenne.fr
                maylis.douine@ch-cayenne.fr
                jerome.ponty@ch-cayenne.fr
                laure.bianco@ch-cayenne.fr
                fatiha.najioullah@chu-martinique.fr
                odile.kilie@chu-martinique.fr
                dominique.catherine@chu-martinique.fr
                nadia.thomas@ch-cayenne.fr
                jean-luc.deshayes@orange.fr
                paul.brousse@ch-cayenne.fr
                gabriel.carles@ch-ouestguyane.fr
                claire.grenier@croix-rouge.fr
                vincent.lacoste@pasteur-cayenne.fr
                vincent.molinie@chu-martinique.fr
                raymond.cesaire@chu-martinique.fr
                mathieu.nacher@ch-cayenne.fr
                Journal
                BMC Womens Health
                BMC Womens Health
                BMC Women's Health
                BioMed Central (London )
                1472-6874
                24 January 2018
                24 January 2018
                2018
                : 18
                : 25
                Affiliations
                [1 ]ISNI 0000 0004 0630 1955, GRID grid.440366.3, Centre d’Investigation Clinique Antilles-Guyane, CIC INSERM 1424, Centre hospitalier de Cayenne, ; Ave des Flamboyants, 97300 Cayenne, French Guiana
                [2 ]GRID grid.412874.c, Laboratoire de Virologie, CHU de la Martinique, ; Fort de France, Martinique
                [3 ]GRID grid.412874.c, Laboratoire d’anatomopathologie, CHU de la Martinique, ; Fort de France, Martinique
                [4 ]ISNI 0000 0004 0630 1955, GRID grid.440366.3, Service de Gynécologie Obstétrique, Centre hospitalier de Cayenne, ; Cayenne, French Guiana
                [5 ]AGDOC Association de Dépistage Organisé des Cancers de Guyane, Cayenne, French Guiana
                [6 ]ISNI 0000 0004 0630 1955, GRID grid.440366.3, Département des Centres délocalisés de prévention et de soins, Centre Hospitalier de Cayenne, 97300, ; Cayenne, French Guiana
                [7 ]Service de Gynécologie Obstétrique, Centre Hospitalier de l’Ouest Guyanais, Saint Laurent du Maroni, Cayenne, French Guiana
                [8 ]ISNI 0000 0001 2206 8813, GRID grid.418525.f, Laboratoire des Interactions Virus-Hôtes, Institut Pasteur de la Guyane, ; Cayenne, French Guiana
                [9 ]GRID grid.460797.b, EA 3593, Ecosystèmes Amazoniens et Pathologie Tropicale, , Université de Guyane, ; Cayenne, French Guiana
                Author information
                http://orcid.org/0000-0001-9397-3204
                Article
                493
                10.1186/s12905-017-0493-9
                5784667
                29368607
                51fd120a-0c8a-48d2-ac8a-69bd8d931ccf
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 23 September 2016
                : 5 December 2017
                Funding
                Funded by: ERDF (European commission)
                Award ID: Presage 30814.
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Obstetrics & Gynecology
                Obstetrics & Gynecology

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