Breast and cervical cancer screening practices in nine countries of Eastern Europe and Central Asia: A population-based survey.

BACKGROUND: Eastern Europe and Central Asia (EECA) countries have higher cervical and breast cancer mortality rates and later stage at diagnosis compared with the rest of WHO European Region. The aim was to explore current early detection practices including "dispensarization" for breast and cervix cancer in the region. METHODS: A questionnaire survey on early detection practices for breast and cervix cancer was sent to collaborators in 11 countries, differentiating services in the primary health setting, and population-based programs. Responses were received from Armenia, Belarus, Georgia, Kazakhstan, Kyrgyzstan, the Russian Federation (Arkhangelsk, Samara and Tomsk regions), Tajikistan, Ukraine, and Uzbekistan. RESULTS: All countries but Georgia, Kyrgyzstan, and the Russian Federation had opportunistic screening by clinical breast exam within "dispensarization" program. Mammography screening programs, commonly starting from age 40, were introduced or piloted in eight of nine countries, organized at national oncology or screening centres in Armenia, Belarus and Georgia, and within primary care in others. Six countries had "dispensarization" program for cervix cancer, mostly starting from the age 18, with smears stained either by Romanowsky-Giemsa alone (Belarus, Tajikistan and Ukraine), or alternating with Papanicolaou (Kazakhstan and the Russian Federation). In parallel, screening programs using Papanicolaou or HPV test were introduced in seven countries and organized within primary care. CONCLUSION: Our study documents that parallel screening systems for both breast and cervix cancers, as well as departures from evidence-based practices are widespread across the EECA. Within the framework of the WHO Initiatives, existing opportunistic screening should be replaced by population-based programs that include quality assurance and control.

Rationale and Purpose: The FLUTE Study to Evaluate Fluorography Mass Screening for Tuberculosis and Other Diseases, as Conducted in Eastern Europe and Central Asia Countries.

In Belarus and several EECA countries, periodic population-based chest X-ray "fluorography programme" use as a mass screening tool for the diagnosis of tuberculosis (TB) has been used for decades. This mass screening has also often been justified for the early detection of lung cancer (LC), although no mortality benefits were demonstrated by screening with chest X-ray in international randomized trials. In Belarus, fluorography testing is mandatory every one to three years for all adults depending on age and the so-called "risk groups". The World Bank and WHO estimate that Belarus spends USD11 million annually on mass fluorography screening and advocate for more targeted screening approaches to increase diagnostic yield for TB and not to use it for screening for LC. The study is a retrospective review of medical records to assess the yield of fluorography to detect true cases of LC and/or TB in asymptomatic patients in two rural and two urban districts in Belarus for 2015-2017 with positive screening results for presumed of TB or LC. The study provided the rationale to implement the improved policy and practices regarding the role of fluorography in the early detection of LC and TB in Belarus and elsewhere.

Progress in reducing premature mortality from cancer and cardiovascular disease in the former Soviet Union, 2000-19.

BACKGROUND: A reduction in non-communicable diseases premature mortality by one-third by 2030 is one of the targets of the UN Sustainable Development Goals (SDG3.4). We examined the mortality profiles in the Newly Independent States of the former Soviet Union (NIS) and the European Union (EU) and assessed progress in reductions of premature mortality from cancer, as compared to cardiovascular disease (CVD). METHODS: We used WHO's Global Health Estimates and GLOBOCAN 2020 to examine current mortality profiles and computed the unconditional probabilities of dying at ages 30-70 from CVD and cancer for the years 2000-19 in both sexes, using a linear extrapolation of this trend to predict whether the target of a one-third reduction, as set in 2015, would be met in 2030. RESULTS: CVD was the main cause of premature death in the NIS (43%), followed by cancer (23%), inversely from the EU with 42% cancer and 24% CVD deaths. The NIS achieved major reductions in premature CVD mortality, although the probabilities of death in 2019 remained about five times higher in the NIS compared to the EU. For cancer, mortality reductions in most NIS were quite modest, other than large declines seen in Kazakhstan (44%) and Kyrgyzstan (30%), with both on course to meet the 2030 target. CONCLUSIONS: Limited progress in cancer control in the NIS calls for policy action both in terms of structural changes towards universal health coverage, and scaling up of national cancer control plans, including a shift from opportunistic to evidence-based early detection practices.

Translating Research to Action: The Development of a Pediatric Palliative Cancer Care Advocacy Tool in Eurasia.

PURPOSE: The Assessing Doctors' Attitudes on Palliative Treatment study was conducted in 11 Eurasian countries to assess physician knowledge of and structural barriers to integration of palliative care into pediatric oncology. After publication, regional collaborators identified the need to disseminate country-specific study results locally and provide policy recommendations to inform stakeholders. METHODS: The Assessing Doctors' Attitudes on Palliative Treatment report was developed with Eurasian and St Jude pediatric palliative care and oncology experts to summarize study findings and deliver country-level data to local stakeholders. In parallel, an assessment was developed to explore how regional collaborators intend to use the report to improve local advocacy and dissemination of research findings. The country report and assessment were translated to English, Russian, and Mongolian. RESULTS: Country-specific two-page reports display study findings on pediatric palliative care education, access to pediatric palliative care services, and barriers to and timing of integration with cancer care, alongside clinical and policy recommendations. These reports were distributed to collaborators in 11 countries. Assessment results (N = 30) demonstrated that regional collaborators planned to distribute the report to institutional and government stakeholders, aiming to increase access to pediatric palliative care services (77%), establish a community-based palliative care network (70%), and increase opportunities for specialization (70%). CONCLUSION: We describe the development of an evidence-based advocacy tool to inform local health and education policy in Eurasia. This summary report of study findings, translated to local languages and adapted to a broader audience, is currently used to advocate for greater access and quality of palliative care for children with cancer. This work may serve as the basis for future dissemination efforts of scientific research.

Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies.

BACKGROUND: Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts. We aimed to evaluate the age-specific prevalence of anal HPV, HSIL, and their combination, in men, stratified by HIV status and sexuality. METHODS: We did a systematic review for studies on anal HPV infection in men and a pooled analysis of individual-level data from eligible studies across four groups: HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive men who have sex with women (MSW), and HIV-negative MSW. Studies were required to inform on type-specific HPV infection (at least HPV16), detected by use of a PCR-based test from anal swabs, HIV status, sexuality (MSM, including those who have sex with men only or also with women, or MSW), and age. Authors of eligible studies with a sample size of 200 participants or more were invited to share deidentified individual-level data on the above four variables. Authors of studies including 40 or more HIV-positive MSW or 40 or more men from Africa (irrespective of HIV status and sexuality) were also invited to share these data. Pooled estimates of anal high-risk HPV (HR-HPV, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), and HSIL or worse (HSIL+), were compared by use of adjusted prevalence ratios (aPRs) from generalised linear models. FINDINGS: The systematic review identified 93 eligible studies, of which 64 contributed data on 29 900 men to the pooled analysis. Among HIV-negative MSW anal HPV16 prevalence was 1·8% (91 of 5190) and HR-HPV prevalence was 6·9% (345 of 5003); among HIV-positive MSW the prevalences were 8·7% (59 of 682) and 26·9% (179 of 666); among HIV-negative MSM they were 13·7% (1455 of 10 617) and 41·2% (3798 of 9215), and among HIV-positive MSM 28·5% (3819 of 13 411) and 74·3% (8765 of 11 803). In HIV-positive MSM, HPV16 prevalence was 5·6% (two of 36) among those age 15-18 years and 28·8% (141 of 490) among those age 23-24 years (ptrend=0·0091); prevalence was 31·7% (1057 of 3337) among those age 25-34 years and 22·8% (451 of 1979) among those age 55 and older (ptrend<0·0001). HPV16 prevalence in HIV-negative MSM was 6·7% (15 of 223) among those age 15-18 and 13·9% (166 of 1192) among those age 23-24 years (ptrend=0·0076); the prevalence plateaued thereafter (ptrend=0·72). Similar age-specific patterns were observed for HR-HPV. No significant differences for HPV16 or HR-HPV were found by age for either HIV-positive or HIV-negative MSW. HSIL+ detection ranged from 7·5% (12 of 160) to 54·5% (61 of 112) in HIV-positive MSM; after adjustment for heterogeneity, HIV was a significant predictor of HSIL+ (aPR 1·54, 95% CI 1·36-1·73), HPV16-positive HSIL+ (1·66, 1·36-2·03), and HSIL+ in HPV16-positive MSM (1·19, 1·04-1·37). Among HPV16-positive MSM, HSIL+ prevalence increased with age. INTERPRETATION: High anal HPV prevalence among young HIV-positive and HIV-negative MSM highlights the benefits of gender-neutral HPV vaccination before sexual activity over catch-up vaccination. HIV-positive MSM are a priority for anal cancer screening research and initiatives targeting HPV16-positive HSIL+. FUNDING: International Agency for Research on Cancer.

The Human Microbiome in Relation to Cancer Risk: A Systematic Review of Epidemiologic Studies.

The microbiome has been hypothesized to play a role in cancer development. Because of the diversity of published data, an overview of available epidemiologic evidence linking the microbiome with cancer is now needed. We conducted a systematic review using a tailored search strategy in Medline and EMBASE databases to identify and summarize the current epidemiologic literature on the relationship between the microbiome and different cancer outcomes published until December 2019. We identified 124 eligible articles. The large diversity of parameters used to describe microbial composition made it impossible to harmonize the different studies in a way that would allow meta-analysis, therefore only a qualitative description of results could be performed. Fifty studies reported differences in the gut microbiome between patients with colorectal cancer and various control groups. The most consistent findings were for Fusobacterium, Porphyromonas, and Peptostreptococcus being significantly enriched in fecal and mucosal samples from patients with colorectal cancer. For the oral microbiome, significantly increased and decreased abundance was reported for Fusobacterium and Streptococcus, respectively, in patients with oral cancer compared with controls. Overall, although there was a large amount of evidence for some of these alterations, most require validation in high-quality, preferably prospective, epidemiologic studies.

Epidemiology of Cancers in Men Who Have Sex with Men (MSM): A Protocol for Umbrella Review of Systematic Reviews.

While earlier studies on men having sex with men (MSM) tended to examine infection-related cancers, an increasing number of studies have been focusing on effects of sexual orientation on other cancers and social and cultural causes for cancer disparities. As a type of tertiary research, this umbrella review (UR) aims to synthesize findings from existing review studies on the effects of sexual orientation on cancer. Relevant peer-reviewed systematic reviews (SRs) will be identified without date or language restrictions using MEDLINE, Cochrane Database of Systematic Reviews, and the International Prospective Register for Systematic Reviews, among others. The research team members will prepare the data extraction forms. Two reviewers will independently assess extracted SRs using the Assessment of Methodological Quality of Systematic Reviews. A third reviewer will weigh in to resolve discrepancies. The reviewers will be blinded to publisher, journal, and authors, making their judgements on the title, year, and abstract. The Preferred Reporting Items for Systematic Reviews and Meta-analysis checklist will guide data synthesis. By collating evidence from multiple reviews into one accessible and usable document, our first UR on global epidemiology of malignancies among MSM would serve as an evidence-based decision-making tool for the public health community.

Appetite-regulating hormones-leptin, adiponectin and ghrelin-and the development of prostate cancer: a systematic review and exploratory meta-analysis.

BACKGROUND: Obesity has been proposed as a risk factor for prostate cancer (PCa). In obesity, serum levels of the appetite-regulating hormones-leptin, adiponectin, and ghrelin-become deregulated. OBJECTIVE: To explore whether serum levels of appetite-regulating hormones associate with the incidence of PCa, the incidence of advanced disease, or PCa-specific mortality. METHODS: PRISMA guidelines were followed. A systematic search for relevant articles published until March 2019 was performed using the databases PubMed, EMBASE, and Web of Science. Observational studies with data on serum levels of leptin, adiponectin, or ghrelin and PCa outcome were included. Meta-analysis was used to combine risk estimates. Meta-relative risks (mRRs) were calculated using random effects models. When available, raw data was pooled. Publication bias was assessed by funnel plot and Begg's test. RESULTS: Thirty-five studies were eligible for inclusion. The qualitative analysis indicated that leptin was not consistently associated with any PCa outcome, although several cohorts reported decreased adiponectin levels in men who later developed advanced PCa. Based on the meta-analysis, there was no significant effect of leptin on PCa incidence (mRR = 0.93 (95% CI 0.75-1.16), p = 0.52) or advanced PCa (mRR = 0.90 (95% CI 0.74-1.10), p = 0.30). There were insufficient studies to estimate the mRR of PCa incidence for men with the highest levels of adiponectin. The combined risk of advanced PCa for men with the highest levels of adiponectin was reduced but did not reach significance (mRR = 0.81 (95% CI 0.61-1.08), p = 0.15). CONCLUSIONS: The current evidence does not suggest an association between leptin and PCa outcome. However, there may be an inverse association between adiponectin and the incidence of advanced PCa that should be investigated by further studies. Serum ghrelin has not been largely investigated.

The European Prostate Cancer Centres of Excellence: A Novel Proposal from the European Association of Urology Prostate Cancer Centre Consensus Meeting.

BACKGROUND: High-quality management of prostate cancer is needed in the fields of clinics, research, and education. OBJECTIVE: The objective of this project was to develop the concept of "European Prostate Cancer Centres of Excellence" (EPCCE), with the specific aim of identifying European centres characterised by high-quality cancer care, research, and education. DESIGN, SETTING, AND PARTICIPANTS: A task force of experts aimed at identifying the general criteria to define the EPCCE. Discussion took place in conference calls and by e-mail from March 2017 to November 2017, and the final consensus meeting named "European Association of Urology (EAU) Prostate Cancer Centre Consensus Meeting" was held in Barcelona on November 16, 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The required criteria were grouped into three main steps: (1) clinics, (2) research, and (3) education. A quality control approach for the three steps was defined. RESULTS AND LIMITATIONS: The definition of EPCCE consisted of the following steps: (1) clinical step-five items were identified and classified as core team, associated services, multidisciplinary approach, diagnostic pathway, and therapeutic pathway; (2) research step-internal monitoring of outcomes was required; clinical data had to be collected through a prespecified database, clinical outcomes had to be periodically assessed, and prospective trials had to be conducted; (3) educational step-it consists of structured fellowship programmes of 1yr, including 6mo of research and 6mo of clinics; and (4) quality assurance and quality control procedures, related to the quality assessment of the previous three steps. A limitation of this project was that the definition of standards and items was mainly based on a consensus among experts rather than being an evidence-based process. CONCLUSIONS: The EAU Prostate Cancer Centre Consensus Meeting defined the criteria for the identification of the EPCCE in the fields of clinics, research, and education. The inclusion of a quality control approach represents the novelty that supports the excellence of these centres. PATIENT SUMMARY: A task force of experts defined the criteria for the identification of European Prostate Cancer Centres of Excellence, in order to certify the high-quality centres for prostate cancer management.

Beta and gamma human papillomaviruses in anal and genital sites among men: prevalence and determinants.

Data regarding the anogenital distribution of and type-specific concordance for cutaneous ß- and γ-HPV types in men who have sex with women is limited and geographically narrow. Knowledge of determinants of anogenital detection of cutaneous HPV types in different regions is needed for better understanding of the natural history and transmission dynamics of HPV, and its potential role in the development of anogenital diseases. Genital and anal canal samples obtained from 554 Russian men were screened for 43 ß-HPVs and 29 γ-HPVs, using a multiplex PCR combined with Luminex technology. Both ß- and γ-HPVs were more prevalent in the anal (22.8% and 14.1%) samples than in the genital (16.8% and 12.3%) samples. Low overall and type-specific concordance for ß-HPVs (3.5% and 1.1%) and γ-HPVs (1.3% and 0.6%) were observed between genital and anal samples. HIV-positive men had higher anal ß- (crude OR = 12.2, 95% CI: 5.3-28.1) and γ-HPV (crude OR = 7.2, 95% CI: 3.3-15.4) prevalence than HIV-negative men. Due to the lack of genital samples from the HIV-positive men, no comparison was possible for HIV status in genital samples. The lack of type-specific positive concordance between genital and anal sites for cutaneous ß- and γ-HPV types in heterosexual men posits the needs for further studies on transmission routes to discriminate between contamination and true HPV infection. HIV-positive status may favor the anal acquisition or modify the natural history of cutaneous HPV types.

Determinants of the presence of human papillomaviruses in the anal canal of Russian men.

Knowledge of determinants of anal human papillomavirus (HPV) infections among men is still limited as most of the studies are focused on high-risk populations and geographically narrowed. Such knowledge obtained in different populations is essential for better understanding of HPV natural history, transmission dynamics, and its role in the development and prevention of anogenital malignancies in different regions. Here we tested anal canal swab samples from 359 Russian heterosexual (323 human immunodeficiency virus [HIV]-negative and 27 HIV-positive, aged 18-67 years) men attending a sexually transmitted infection clinic 36 HPV types using a proficient Luminex assay. HPV-positivity in anal samples was common for 332 HIV-negative heterosexual men for overall HPV (15.7%, n = 52), oncogenic HPV (9.6%, n = 32), nononcogenic HPV (8.1%, n = 27), and multiple HPV infections (4.5%, n = 14). The most common anal HPV types were HPV16 (5.7%), HPV45, and HPV51 (1.8% each), HPV66, and HPV87 (1.8% each). No association was found with the number of lifetime sexual partners, age of participants at the time of the study, or their sexual debut. Although anal HPV positivity was more common among HIV-positive men, the current study provides additional evidence that anal HPV can be frequently detected in heterosexual HIV-negative men favoring further studies on transmission routes to discriminate between contamination and true HPV infection.

Prevalence of cutaneous beta and gamma human papillomaviruses in the anal canal of men who have sex with women.

BACKGROUND: Data regarding anal cutaneous HPV detection among HIV-positive and HIV-negative persons largely relies on studies among men who have sex with men in limited geographical settings. Understanding the distribution, determinants, and potential human health effects of anal cutaneous HPV types among men who have sex with women (MSW) is important. METHODS: Anal canal swab samples from 415 Russian MSW (384 HIV-negative and 31 HIV-positive) were tested for 43 ß-HPVs and 29 γ-HPVs, using a multiplex PCR combined with Luminex technology. RESULTS: ß-HPV was detected in 24.4% and γ-HPV in 15.9% of anal samples of all Russian MSW. In total, 34 ß-HPV and 19 γ-HPV types were detected, with the most commonly detected ß-HPV types being 110, 22 and 124 and the most common γ-HPV types being 95, 132 and 50. For both genera, being HIV-positive at the time of testing was a significant determinant of detection (74.2% for ß-HPVs and 48.4% for γ-HPVs compared to 20.1% and 12.5% in HIV-negative MSW, respectively). CONCLUSIONS: A wide spectrum and moderate prevalence of anal ß-HPV and γ-HPV types was found in our MSW study sample, suggesting that routes other than penile-anal intercourse may be important in cutaneous HPV transmission.

Lack of Significant Effects of Chlamydia trachomatis Infection on Cervical Adenocarcinoma Risk: Nested Case-Control Study.

BACKGROUND: A role of Chlamydia trachomatis in HPV-induced cervical carcinogenesis has been reported for cervical cancer but studies on cervical adenocarcinoma are limited. METHODS: A total of 1,553 cervical smears taken up to 26 years before diagnosis in a large population-based nested case-control study of cervical adenocarcinoma (AC, 132 cases with matched controls), and adenocarcinoma in situ (AIS, 159 cases with matched controls) were tested for C. trachomatis and HPV DNA by a type-specific PCR bead-based multiplex genotyping (TS-MPG) assay. RESULTS: Only 1.7% of samples were positive for C. trachomatis, with no significant differences between AC/AIS cases and controls. HPV-positivity was detected in 49.3% of C. trachomatis-negative and 65.4% C. trachomatis-positive samples, respectively. CONCLUSIONS: A large prospective study did not find any risk for cervical adenocarcinoma and/or AIS conferred by C. trachomatis infection. IMPACT: C. trachomatis appears not to be involved in cervical adenocarcinomas.

Detection of DNA viruses in prostate cancer.

We tested prostatic secretions from men with and without prostate cancer (13 cases and 13 matched controls) or prostatitis (18 cases and 18 matched controls) with metagenomic sequencing. A large number (>200) of viral reads was only detected among four prostate cancer cases (1 patient each positive for Merkel cell polyomavirus, JC polyomavirus and Human Papillomavirus types 89 or 40, respectively). Lower numbers of reads from a large variety of viruses were detected in all patient groups. Our knowledge of the biology of the prostate may be furthered by the fact that DNA viruses are commonly shed from the prostate and can be readily detected by metagenomic sequencing of expressed prostate secretions.

Alpha, beta and gamma Human Papillomaviruses in the anal canal of HIV-infected and uninfected men who have sex with men.

OBJECTIVES: Anal infection by cutaneous Human Papillomaviruses (HPV) has been rarely investigated. We aimed to assess the prevalence, genotype diversity, and determinants of mucosal (alpha) and cutaneous (beta and gamma) anal HPV infection in men who have sex with men (MSM). METHODS: Anal samples were collected with a Dacron swab. Alpha HPVs were detected using the Linear Array HPV genotyping test, while beta and gamma HPVs using a PCR combined with Luminex technology. RESULTS: A total of 609 MSM (437 HIV-uninfected and 172 HIV-infected, most of which were undergoing cART) were enrolled. Alpha, beta, and gamma HPVs were detected in 78.0%, 27.6% and 29.3% of the participants. Only alpha HPV prevalence was significantly higher among HIV-infected compared to uninfected MSM (93.0% vs. 72.1%, p < 0.0001). Beta2 and gamma10 represented the most frequent cutaneous HPV species, with no significant differences between HIV-infected and uninfected individuals. The most common alpha, beta, and gamma genotypes were HPV16, HPV111, HPV121, respectively. Alpha HPV infection was significantly associated with lifetime number of partners, receptive anal sex, and HIV status. Beta and/or gamma HPV infection showed no significant association with HIV status, socio-demographic or sexual behavioral factors. CONCLUSIONS: A wide spectrum of mucosal and cutaneous HPV types is present in the anal canal. Only mucosal HPV prevalence increased significantly in cases of concomitant HIV infection.

Long-term HPV type-specific risks of high-grade cervical intraepithelial lesions: a 14-year follow-up of a randomized primary HPV screening trial.

Quantitative knowledge of the long-term human papillomavirus (HPV) type-specific risks for high-grade cervical intraepithelial neoplasias Grades 2 and 3 (CIN2 and CIN3) is useful for estimating the effect of elimination of specific HPV types and clinical benefits of screening for specific HPV types. We estimated HPV type-specific risks for CIN2 and CIN3 using a randomized primary HPV screening trial followed up for 14.6 years using comprehensive, nationwide registers. Poisson regression estimated cumulative incidences, population attributable proportions (PAR) and incidence rate ratios (IRRs) of high-grade lesions by baseline HPV type, with censoring at date of first CIN2/3 or last registered cytology. Multivariate analysis adjusted for coinfections. IRRs were highest during the first screening round, but continued to be high throughout follow-up (IRRs for CIN3 associated with high-risk (HR) HPV positivity were 226.9, 49.3, 17.7 and 10.3 during the first, second and third screening round and for >9 years of follow-up, respectively). Increased long-term risks were found particularly for HPV Types 16, 18 and 31 and for CIN3+ risks. HPV16/18/31/33 had 14-year cumulative incidences for CIN3+ above 28%, HPV35/45/52/58 had 14 year risks between 14% and 18% and HPV39/51/56/59/66/68 had risks <10%. HPV16 contributed to the greatest proportion of CIN2+ (first round PAR 36%), followed by Types 31, 52, 45 and 58 (7-11%). HPV16/18/31/33/45/52/58 together contributed 73.9% of CIN2+ lesions and all HR types contributed 86.9%. In summary, we found substantial differences in risks for CIN2 and CIN3 between different oncogenic HPV types. These differences may be relevant for both clinical management and design of preventive strategies.

Long-term HPV type-specific risks for ASCUS and LSIL: a 14-year follow-up of a randomized primary HPV screening trial.

Human papillomavirus (HPV) infections result in a significant burden of low-grade cervical lesions. Between 1997 and 2000, our randomized trial of primary HPV screening enrolled 12,527 women participating in population-based screening. Women between 32 and 38 years of age (median: 34, interquartile range: 33-37) were randomized to HPV and cytology double testing (intervention arm, n = 6,257 enrolled, n = 5,888 followed-up) or to cytology, with samples frozen for future HPV testing (control arm, n = 6,270 enrolled, n = 5,795 followed-up). We estimated the HPV type-specific, long-term absolute risks (AR), and population attributable proportions (PAR) for cytological diagnoses of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) and for histopathologically diagnosed cervical intraepithelial neoplasia grade 1 (CIN1). The women were followed using comprehensive, nationwide register-based follow-up. During a mean follow-up time of 11.07 years, 886 ASCUS and LSIL lesions were detected, 448 in the intervention arm and 438 in the control arm. Poisson regression estimated the incidence rate ratios (IRRs) of low-grade lesions by HPV type. The IRRs were strongly dependent on follow-up time. The IRRs for ASCUS/LSIL associated with high-risk HPV positivity were 18.6 (95% CI: 14.9-23.4) during the first screening round, 4.1 (95% CI: 2.8-6.2) during the second, 2.6 (95% CI: 1.7-4.1) during the third, and 1.1 (95% CI: 0.7-1.8) for >9 years of follow-up, with similar declines seen for the individual types. Type 16 contributed consistently to the greatest proportion of ASCUS, LSIL, and CIN1 risk in the population (first screening round PAR: ASCUS: 15.5% (95% CI: 9.7-21.9), LSIL: 14.7% (95% CI: 8.0-20.9), and CIN1: 13.4% (95% CI: 3.2-22.5)), followed by type 31 [8.4% (95% CI: 4.2-12.5) for ASCUS to 17.3% (95% CI: 6.8-26.6) for CIN1]. In summary, most ASCUS/LSIL lesions associated with HPV infection are caused by new HPV infections and most lesions are found during the first screening round.

Metagenomic sequencing of expressed prostate secretions.

To investigate which microorganisms may be present in expressed prostate secretions (EPS) metagenomic sequencing (MGS) was applied to prostate secretion samples from five men with prostatitis and five matched control men as well as to combined expressed prostate secretion and urine from six patients with prostate cancer and six matched control men. The prostate secretion samples contained a variety of bacterial sequences, mostly belonging to the Proteobacteria phylum. The combined prostate secretion and urine samples were dominated by abundant presence of the JC polyomavirus, representing >20% of all detected metagenomic sequence reads. There were also other viruses detected, for example, human papillomavirus type 81. All combined prostate secretion and urine samples were also positive for Proteobacteria. In summary, MGS of expressed prostate secretion is informative for detecting a variety of bacteria and viruses, suggesting that a more large-scale use of MGS of prostate secretions may be useful in medical and epidemiological studies of prostate infections.

Long term duration of protective effect for HPV negative women: follow-up of primary HPV screening randomised controlled trial.

OBJECTIVES: To assess whether the increased sensitivity of screening for human papillomavirus (HPV) may represent overdiagnosis and to compare the long term duration of protective effect against cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in HPV based and cytology based screening. DESIGN: 13 year follow-up of the Swedescreen randomised controlled trial of primary HPV screening. SETTING: Organised cervical screening programme in Sweden. PARTICIPANTS: 12,527 women aged 32-38 attending organised screening were enrolled and randomised to HPV and cytology double testing (intervention arm, n=6257) or to cytology only, with samples frozen for future HPV testing (control arm, n=6270). MAIN OUTCOME MEASURES: Cumulative incidence of CIN2+ and CIN3+ (Kaplan Meier curves). Longitudinal test characteristics were calculated for cytology only, HPV testing only, and cytology and HPV testing combined, adjusting for censoring. RESULTS: The increased detection of CIN2+ in the intervention arm decreased over time. After six years, the cumulative incidence of CIN3+ was similar in both trial arms, and after 11 years the cumulative incidence of CIN2+ became similar in both arms. The longitudinal sensitivity of cytology for CIN2+ in the control arm at three years was similar to the sensitivity of HPV testing in the intervention arm at five years of follow-up: 85.94% (95% confidence interval 76.85% to 91.84%) v 86.40% (79.21% to 91.37%). The sensitivity of HPV screening for CIN3+after five years was 89.34% (80.10% to 94.58%) and for cytology after three years was 92.02% (80.59% to 96.97%). CONCLUSIONS: Over long term follow-up, the cumulative incidence of CIN2+ was the same for HPV screening and for cytology, implying that the increased sensitivity of HPV screening for CIN2+ reflects earlier detection rather than overdiagnosis. The low long term risks of CIN3+ among women who tested negative in HPV screening, support screening intervals of five years for such women. TRIAL REGISTRATION: Clinicaltrials.gov NCT00479375.