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International audience; We assessed bone mineral density (BMD) in a cohort of human immunodeficiency virus (HIV)-positive patients after a median of 11 years of combination antiretroviral therapy (cART) and evaluated the respective role of HIV infection and antiretroviral drugs (ARVs). A cross-sectional study of 162 participants (131 male) from the ANRS-C08 cohort was performed with bone dual-energy X-ray absorptiometry (DXA) scans and renal assessment. The window of exposure to ARVs was defined as an exposure of more than six cumulative months during the last 3 years before the DXA evaluation to account for a cumulative exposure that could affect bone remodeling. The association with low BMD (Z-score < -2) was assessed by a multiple logistic regression model. The study population was 50 years (median), hepatitis C virus (HCV) (18%), and hepatitis B virus (HBV) (8%) coinfection with HIV-RNA

Cervical cancer screening will rely, increasingly, on HPV testing as a primary screen. The requirement for triage tests which can delineate clinically significant infection is thus prescient. In this EUROGIN 2017 roadmap, justification behind the most evidenced triages is outlined, as are challenges for implementation. Cytology is the triage with the most follow-up data; the existence of an HR-HPV positive, cytology negative group presents a challenge and re-testing intervals for this group (and choice of re-test) require careful consideration. Furthermore, cytology relies on subjective skills and while adjunctive dual-staining with p16/Ki67 can mitigate inter-operator/site disparities, clinician-taken samples are required. Comparatively, genotyping and methylation markers are objective and are applicable to self-taken samples, offering logistical advantages including in low and middle income settings. However, genotyping may have diminishing returns in immunised populations and type(s) included must balance absolute risk for disease to avoid low specificity. While viral and cellular methylation markers show promise, more prospective data are needed in addition to refinements in automation. Looking forward, systems that detect multiple targets concurrently such as next generation sequencing platforms will inform the development of triage tools. Multi-step triage strategies may be be beneficial provided they do not create complex, unmanageable pathways. Inevitably, the balance of risk to cost(s) will be key in decision making, although defining an acceptable risk will likely differ between settings. Finally, given the significant changes to cervical screening and the variety of triage strategies, appropriate education of both health care providers and the public is essential.

Human papillomaviruses (HPVs) are the necessary cause of most cervical cancers, a large proportion of other anogenital cancers, and a subset of oropharyngeal cancers. The knowledge about HPV has led to development of novel HPV-based prevention strategies with important impact on clinical and public health practice. Two complementary reviews have been prepared following the 2015 Eurogin Conference to evaluate how knowledge about HPV is changing practice in HPV infection and disease control through vaccination and screening. This review focuses on screening for cervical and anal cancers in increasingly vaccinated populations. The introduction of HPV vaccines a decade ago has led to reductions in HPV infections and early cancer precursors in countries with wide vaccination coverage. Despite the high efficacy of HPV vaccines, cervical cancer screening will remain important for many decades. Many healthcare systems are considering switching to primary HPV screening, which has higher sensitivity for cervical precancers and allows extending screening intervals. We describe different approaches to implementing HPV-based screening efforts in different healthcare systems with a focus in high-income countries. While the population prevalence for other anogenital cancers is too low for population-based screening, anal cancer incidence is very high in HIV-infected men who have sex with men, warranting consideration of early detection approaches. We summarize the current evidence on HPV-based prevention of anal cancers and highlight important evidence gaps.

Human papillomaviruses (HPVs) are the necessary cause of most cervical cancers, a large proportion of other anogenital cancers, and a subset of oropharyngeal cancers. The knowledge about HPV has led to development of novel HPV-based prevention strategies with important impact on clinical and public health practice. Two complementary reviews have been prepared following the 2015 Eurogin Conference to evaluate how knowledge about HPV is changing practice in HPV infection and disease control through vaccination and screening. This review focuses on screening for cervical and anal cancers in increasingly vaccinated populations. The introduction of HPV vaccines a decade ago has led to reductions in HPV infections and early cancer precursors in countries with wide vaccination coverage. Despite the high efficacy of HPV vaccines, cervical cancer screening will remain important for many decades. Many healthcare systems are considering switching to primary HPV screening, which has higher sensitivity for cervical precancers and allows extending screening intervals. We describe different approaches to implementing HPV-based screening efforts in different healthcare systems with a focus in high-income countries. While the population prevalence for other anogenital cancers is too low for population-based screening, anal cancer incidence is very high in HIV-infected men who have sex with men, warranting consideration of early detection approaches. We summarize the current evidence on HPV-based prevention of anal cancers and highlight important evidence gaps. NW was supported by the Intramural Research Program of the National Cancer Institute, Z01 CP010124-21. MA received support from the 7th Framework Program of Research of the European Commission through the CoheaHr Project; Grant number: 603019

International audience; BACKGROUND: The aim of our study was to determine whether HIV-1 DNA level before antiretroviral therapy (ART) was associated with short- and long-term virological and immunological responses. METHODS: Patients starting first-line protease inhibitor-containing regimens were enrolled in a prospective multicentre cohort in 1998-99. HIV-1 DNA was quantified using real-time PCR at baseline and after 1 year of ART. The association between HIV-1 DNA and virological and immunological responses after 1 and 7 years on ART was studied in multivariate regression models along with other biological and clinical variables. Virological failure (VF) at month 12 (M12) was defined as a plasma HIV-1 RNA >500 copies/mL. Time to death or two plasma HIV-1 RNA >500 copies/mL between M12 and M84 was studied for long-term VF. RESULTS: HIV-1 DNA levels were measured in 148 patients. The median baseline peripheral blood mononuclear cell (PBMC) HIV-1 DNA was 3.7 log(10) copies/10(6) PBMCs. At M12, the median PBMC HIV-1 DNA was 2.99 log(10) copies/10(6) PBMCs. The median decrease in PBMC HIV-1 DNA between M0 and M12 was -0.7 log(10) copies/10(6) PBMCs. Higher baseline PBMC HIV-1 DNA and plasma HIV-1 RNA were independently associated with a higher risk of VF at M12. Only the baseline plasma HIV-1 RNA was independently associated with long-term virological response. The baseline CD4 cell count was the only parameter associated with short- and long-term immunological responses. CONCLUSIONS: HIV-1 DNA impacted the virological response in our cohort. Further research is warranted to study the impact of HIV-1 DNA with currently recommended first-line cART.

The present study reports results obtained with DNA ploidy measurement by Feulgen cytophotometry and in situ hybridization (ISH) on the same sections of 36 cervical lesions containing human papillomavirus (HPV) DNA. Fifteen of 16 low grade lesions [11 flat condylomas and five condylomatous with intraepithelial neoplasias (CIN)-1, 1 with condylomatous features] were diploid. "Oncogenic" HPV (types 16 and 33) were detected in three of these cases, while the aneuploid case expressed HPV type 11. By contrast, in the 12 CIN-2 and eight CIN-3 with condylomas, there was a good correlation between presence of an aneuploid DNA pattern and detection of "oncogenic" HPVs. Demonstration of an aneuploid profile and "oncogenic" HPV as found in all our CIN-3, may indicative of a poor prognosis in low grade lesions. Hence, the combination of the two techniques (ISH and Feulgen cytophotometry) may provide significant prognostic information for condylomas and CINs.

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Infection with high-risk human papillomavirus (HR HPV) has been implicated as the main and sole cause of cervical cancer. In Europe HR HPV 18, 33 and 31 are the most frequently found after HPV 16 that account for more than 60% of cases (1). HR HPV 52 and 58 are less frequent in Europe but not uncommon worldwide, especially in Asia. The aim of this study was to evaluate the prevalence of HPV 52 and 58 among Croatian women. Thus, women with cytological abnormalities, aged 15 to 78 years, were included for HPV DNA detection by polymerase chain reaction (PCR) using two sets of universal primers (MY09/MY11 and L1C1/L1C2) as previously described (2). HPV types 6/11, 16, 18, 31, 33, 52 and 58 were determined by type-specific primers directed PCR. Out of 2, 241 specimens, 60.9 and 39.1% was HPV DNA positive and negative, respectively. As a sole infection the most frequently observed type was HPV 16 in 11.4% cases. The second most frequent HR type was HPV 31 found in 5.5% cases. HR HPV 18, 33 and 52 were found in almost equal proportions in 2.4, 2.7 and 2.6%, respectively. HR HPV 58 was the less frequently found in 1% cases. Additionally, LR HPV 6/11 and multiple HPV infections were both found in 5.8% cases, respectively. Among HPV DNA positive samples 23.7% samples remained untyped. Our results indicate that HPV 16 is the most common, while HPV 31 is the second most common HR HPV type among Croatian women ; HPV 52 is as frequent as HPV 18 and 33 that are the third most common HR HPV ; HPV 58 seems uncommon HR HPV type. According to our finding all HPV positive abnormal cervical specimens in Croatia should be typed for at least HR HPV 16, 18, 31, 33 and 52. (1)Clifford GM et al. Br J Cancer 2003 ; 88: 63-73. (2)Grce M et al., Anticancer Res 2001 ; 21: 579-584.

OBJECTIVE: Success in diagnoses of cervical carcinoma is due to the population-wide screening protocols which allow identifying early precancerogenic lesions by the use of cytological smear analysis. Based on the understanding of the molecular pathogenesis of cervical cancer and the key role of the human papilloma virus oncogenes, the cyclin-dependent kinase inhibitor p16INK4a emerged as an biomarker to identify HPV-infected cells in histological and cytological slides. Protein p16INK4a was named as a diagnostic marker for cervical dysplasia.PURPOSE OF THE STUDY was to exam the potential of p16 INK4a as a biomarker for oncogenic HPV infection in cervical lesions.MATERIAL AND METHODS: Conventional Pap-smears were taken from 79 patients, analyzed and quategorisated by Bethesda into normal epithelium (14 patients), low grade (LG SIL)(24), high grade lesion (HG SIL)(31) and squamous carcinoma (10). Simultaneously, fifty-two (52) slides were taken for immunoassaying with p16INK4a and twenty-seven (27) were decolorized in diluted solution of HCl, rinsed with distilled water and immunocytochemically stained. High risk HPV infection was documented in all high grade and ca patients (100%), and in 15 patients with low grade lesion (62, 5%). Forty-one patients underwent colposcopy and/or operation so histological diagnoses were made.RESULTS: Cells are regarded as stained in which p16INK4a was expressed in nuclei and/or in a cytoplasm.There was sporadic positivity in, mainly , metaplastic cells but only in their cytoplasms. The portion of p16INK4a-positive samples increases in the following row: normal (1/14 - 7, 14%) - LG SIL (7/24 - 29, 16%) - HG SIL (100%) – carcinoma (100%). CONCLUSION: In spite of sporadic positivity of normal metaplastic cells use of p16INK4a may be regarded as a supplementary test for diagnostics of cervical dysplasia. Overexpression of the protein p16INK4a is typical for lesions where the persistent HPV infection exist (neoplastic and high grade lesion), although it seemed that another trigger is necessary for LG lesion so cells may switch into a process of carcinogenesis.