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Objectives The aim of this study was to estimate how well the excess mortality reflected the burden of coronavirus disease 2019 (COVID-19)-related deaths during the March–May 2020 COVID-19 outbreak in Stockholm, Sweden, and whether the excess mortality during the outbreak might have resulted in a compensatory reduced mortality after the outbreak. Methods Using previous 10-year or 5-year average mortality rates as a baseline, the excess mortality estimates before, during, and after the COVID-19 outbreak in March–May 2020 in Stockholm were compared. Results Weekly death estimates revealed that the immediate pre-outbreak and post-outbreak all-cause mortality did not exceed to excess mortality regardless of whether previous 10-year or 5-year average mortality was used. Forty-three days after the start of the outbreak, 74.4% of the total excess mortality was reportedly explained by known COVID-19-related deaths, and the present study reports an update, showing that 15 weeks after the start of the outbreak, the reported COVID-19-related deaths explained >99% of the total excess mortality. Conclusions An exceptional outbreak feature of rapid excess mortality was observed. However, no excess but similarly low mortality was observed immediately prior to the outbreak and post-outbreak, thus emphasizing the severity of the first wave of the COVID-19 outbreak in Stockholm.

After the European colonization of the Americas, there was a dramatic population collapse of the Indigenous inhabitants caused in part by the introduction of new pathogens. Although there is much speculation on the etiology of the Colonial epidemics, direct evidence for the presence of specific viruses during the Colonial era is lacking. To uncover the diversity of viral pathogens during this period, we designed an enrichment assay targeting ancient DNA (aDNA) from viruses of clinical importance and applied it to DNA extracts from individuals found in a Colonial hospital and a Colonial chapel (16th-18th century) where records suggest that victims of epidemics were buried during important outbreaks in Mexico City. This allowed us to reconstruct three ancient human parvovirus B19 genomes and one ancient human hepatitis B virus genome from distinct individuals. The viral genomes are similar to African strains, consistent with the inferred morphological and genetic African ancestry of the hosts as well as with the isotopic analysis of the human remains, suggesting an origin on the African continent. This study provides direct molecular evidence of ancient viruses being transported to the Americas during the transatlantic slave trade and their subsequent introduction to New Spain. Altogether, our observations enrich the discussion about the etiology of infectious diseases during the Colonial period in Mexico.The arrival of European colonists to the Americas, beginning in the 15

Viruses infecting humans are manifold and several of them provoke significant morbidity and mortality. Simulations creating large synthetic datasets from observed multiple viral strain infections in a limited population sample can be a powerful tool to infer significant pathogen occurrence and interaction patterns, particularly if limited number of observed data units is available. Here, to demonstrate diverse human papillomavirus (HPV) strain occurrence patterns, we used log-linear models combined with Bayesian framework for graphical independence network (GIN) analysis. That is, to simulate datasets based on modeling the probabilistic associations between observed viral data points, i.e different viral strain infections in a set of population samples. Our GIN analysis outperformed in precision all oversampling methods tested for simulating large synthetic viral strain-level prevalence dataset from observed set of HPVs data. Altogether, we demonstrate that network modeling is a potent tool for creating synthetic viral datasets for comprehensive pathogen occurrence and interaction pattern estimations.

The origins of viral pathogens and the age of their association with humans remains largely elusive. To date, there is no direct evidence about the diversity of viral infections in early modern humans pre-dating the Holocene. We recovered two near-complete genomes (5.2X and 0.7X) of human adenovirus C (HAdV-C), as well as low-coverage genomes from four distinct species of human herpesvirus obtained from two 31,630-year-old milk teeth excavated at Yana, in northeastern Siberia. Phylogenetic analysis of the two HAdV-C genomes suggests an evolutionary origin around 700,000 years ago consistent with a common evolutionary history with hominin hosts. Our findings push back the earliest direct molecular evidence for human viral infections by ∼25,000 years, and demonstrate that viral species causing common childhood viral infections today have been in circulation in humans at least since the Pleistocene.

Most Covid-related infections and deaths occur in healthcare outside hospitals. We wished to explore SARS-CoV-2 infections among healthcare workers (HCWs) in this setting. All healthcare providers in Stockholm, Sweden were asked to invite HCWs at work for a study of past or present SARS-CoV-2 infections among HCWs. This study reports the results from 839 HCWs, mostly employees of primary care centers, sampled in June 2020. Prior infection, as measured using seropositivity, was found among 12% (100/839) of HCWs, ranging from 0–29% between care units. There was a significant trend of decreasing serology positivity by age (one sided p-trend 0.0467). Seropositivity was highest among HCWs

Total excess mortality peaked during a coronavirus disease 2019 (COVID-19) outbreak in Stockholm, but 25% of these deaths were not recognized as COVID-19 related nor occurred in hospitals. Estimate of total excess mortality may give a more comprehensive picture of the total disease burden during a COVID-19 outbreak, and may facilitate managing future outbreaks.

Background Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity among asymptomatic subjects reflects past or future disease may be difficult to ascertain. Methods We tested 9449 employees at Karolinska University Hospital, Stockholm, Sweden for SARS-CoV-2 RNA and antibodies, linked the results to sick leave records, and determined associations with past or future sick leave using multinomial logistic regression. Results Subjects with high amounts of SARS-CoV-2 virus, indicated by polymerase chain reaction (PCR) cycle threshold (Ct) value, had the highest risk for sick leave in the 2 weeks after testing (odds ratio [OR], 11.97; 95% confidence interval [CI], 6.29–22.80) whereas subjects with low amounts of virus had the highest risk for sick leave in the 3 weeks before testing (OR, 6.31; 95% CI, 4.38–9.08). Only 2.5% of employees were SARS-CoV-2 positive while 10.5% were positive by serology and 1.2% were positive in both tests. Serology-positive subjects were not at excess risk for future sick leave (OR, 1.06; 95% CI, .71–1.57). Conclusions High amounts of SARS-CoV-2 virus, as determined using PCR Ct values, was associated with development of sickness in the next few weeks. Results support the concept that PCR Ct may be informative when testing for SARS-CoV-2. Clinical Trials Registration. NCT04411576.

Objectives Most COVID-19 related infections and deaths may occur in healthcare outside hospitals. Here we explored SARS-CoV-2 infections among healthcare workers (HCWs) in this setting. Design All healthcare providers in Stockholm, Sweden were asked to recruit HCWs at work for a study of past or present SARS-CoV-2 infections among HCWs. Study participants This study reports the results from 839 HCWs, mostly employees of primary care centers, sampled in June 2020. Results SARS-CoV-2 seropositivity was found among 12% (100/839) of HCWs, ranging from 0% to 29% between care units. Seropositivity decreased by age and was highest among HCWs Conclusions Previous SARS-CoV-2 infections were common among younger HCWs in this setting. Pre-symptomatic infection was uncommon, in line with the strong variability in SARS-CoV-2 exposure between units. Prioritizing infection prevention and control including sufficient and adequate personal protective equipment, and vaccination for all HCWs are important to prevent nosocomial infections and infections as occupational injuries during an ongoing pandemic.

Background Cervical cancer elimination through human papillomavirus (HPV) vaccination programs requires the attainment of herd effect. Due to its uniquely high basic reproduction number, the vaccination coverage required to achieve herd effect against HPV type 16 exceeds what is attainable in most populations. We have compared how gender-neutral and girls-only vaccination strategies create herd effect against HPV16 under moderate vaccination coverage achieved in a population-based, community-randomized trial. Methods and findings In 2007–2010, the 1992–1995 birth cohorts of 33 Finnish communities were randomized to receive gender-neutral HPV vaccination (Arm A), girls-only HPV vaccination (Arm B), or no HPV vaccination (Arm C) (11 communities per trial arm). HPV16/18/31/33/35/45 seroprevalence differences between the pre-vaccination era (2005–2010) and post-vaccination era (2011–2016) were compared between all 8,022 unvaccinated women, Author summary Why was this study done? High-risk human papillomavirus (HPV) infection is a necessary cause of cervical cancer in females. HPV vaccination targeting high-risk HPV types 16 and 18 has been implemented internationally. Achieving herd protection for HPV16 may require greater than 80% girls-only vaccination coverage, a level that has not been achievable in many countries. We evaluate whether gender-neutral or girls-only HPV vaccination results in HPV16 and HPV18 herd protection when the vaccination coverage is only moderate (40%–50%). What did the researchers do and find? We implemented a community-randomized trial of gender-neutral versus girls-only versus no HPV vaccination of young adolescents in 2007–2010, with 11 communities in each arm. Vaccination coverage was implemented with moderate coverage (40%–50%) at the community level. We evaluated the herd effect created by the different vaccination strategies by measuring the cumulative incidence of vaccine-protected HPV types in 8,022 young unvaccinated pregnant females (under 23 years old), comparing the time periods 2005–2010 (pre-vaccination) and 2011–2016 (post-vaccination). An HPV16 herd effect, that is, a reduction in cumulative incidence among the unvaccinated females, was only observed in communities where gender-neutral vaccination had been implemented. What do these findings mean? Achieving a vaccination coverage of above 80%, which is required to achieve herd effect against HPV16, may be unrealistic in some populations. Implementing gender-neutral HPV vaccination provides a solution to this problem as the vaccination coverage threshold required to provide herd effect to unvaccinated females is lower. Our study finds that gender-neutral vaccination provides stronger herd effect than girls-only vaccination in the setting of moderate vaccination coverage. However, these findings are limited to this setting and are not readily generalizable to settings with high (>80%) vaccination coverage.

BackgroundPre-symptomatic subjects are spreaders of SARS-CoV-2 infection, and strategies that could identify these subjects, particularly in hospital settings, are needed.MethodsWe tested a cohort of 9449 employees at work at the Karolinska University Hospital, Stockholm, Sweden for SARS-CoV-2 RNA and antibodies, linked the screening results to sick leave records and examined the association between screening results and past or future sick leave using multinomial logistic regression.ResultsWe found that healthcare workers with high amounts of SARS-CoV-2 virus, as indicated by the Cycle threshold (Ct) value in the PCR, had the highest risk for sick leave in the two weeks after testing (OR 11·97 (CI 95% 6·29-22·80)) whereas subjects with low amounts of virus had the highest risk for sick leave in the past three weeks before testing (OR 6·31 (4·38-9·08)). Only 2·5% of employees were SARS-CoV-2 positive while 10·5% were positive by serology and 1·2% were positive in both tests. Serology-positive subjects were not at excess risk for future sick leave (OR 1·06 (95% CI, 0·71-1·57)), but virus-positive subjects had a 7·23 fold (95% CI, 4·52-11·57)) increased risk for sick leave within two weeks post testing.ConclusionsScreening of asymptomatic healthcare workers for high amounts of SARS-CoV-2 virus using Ct values will identify pre-symptomatic subjects who will develop disease in the next few weeks. Identification of potentially contagious, pre-symptomatic subjects is likely critical for protecting patients and healthcare workers.Main pointHealthy healthcare workers with low amounts of SARS-CoV-2 nucleic acids will previously have had the disease. Presence of a high amount of SARS-CoV-2 nucleic acids predicts future symptomatic disease.

We compared the total excess mortality per week in relation to the reported Covid-19 related deaths in the Stockholm region (Sweden). Total excess mortality peaked under the weeks of high COVID-19-related mortality, but 25% of these deaths were not recognized as Covid-related. Most of these deaths occurred outside hospitals. Total all-cause mortality in excess to average all-cause mortality during the epidemic peak period may provide a comprehensive picture of the total burden of COVID19-related deaths.

BackgroundTransfusion of convalescent immune plasma (CP) is commonly used in epidemics. Several articles now describe clinical report data of CP for treatment of SARS-CoV-2-induced COVID-19 disease.MethodsA systematic literature review was conducted using the NCBI curated COVID-19 related open-resource literature database LitCovid to identify studies using CP as treatment for COVID-19 patients. We retrieved and curated all COVID-19 related patient and treatment characteristics from previously reported studies. A Poisson model was developed to evaluate the association between age of the patients, older age being the most common risk factor for COVID-19 mortality, and recovery time since CP treatment using data extracted from the literature.ResultsFrom 18,293 identified COVID-19 related articles, we included ten studies reporting results of CP treatment for COVID-19 from a total of 61 patients. Decreased symptoms of severe COVID-19 and clearance of SARS-CoV-2 RNA were the most direct observations. We found that patients over the age of sixty who received CP treatment for COVID-19 had a significantly prolonged recovery estimated by viral clearance (from 10 to 29 days since first dose of CP) compared to younger patients, who recovered from the infection in less than a week after receiving CP treatment.ConclusionsLimited published results on plasma transfusion treatment for COVID-19 disease with concomitant treatments suggest that CP therapy for COVID-19 is well tolerated and effective. First randomized clinical trial results, however, revealed no improvements in recovery time for elderly patients with severe COVID-19 between standard treatment alone and added with convalescent plasma. Accordingly, we argue that older patients may need a significantly longer time for recovery. Further randomized clinical trial data for COVID-19 with rigorous ethical standards is urgently needed.

Large scale human papillomavirus (HPV) vaccination against the most oncogenic high-risk human papillomavirus (HPV) types 16/18 is rapidly reducing their incidence. However, attempts at assessing if this leads to an increase of nonvaccine targeted HPV types have been hampered by several limitations, such as the inability to differentiate secular trends. We performed a population-based serological survey of unvaccinated young women over 12 years. The women were under 23-years-old, residents from 33 communities which participated in a community-randomised trial (CRT) with approximately 50% vaccination coverage. Serum samples were retrieved pre-CRT and post-CRT implementation. Seropositivity to 17 HPV types was assessed. HPV seroprevalence ratios (PR) comparing the postvaccination to prevaccination era were estimated by trial arm. This was also assessed among the sexual risk-taking core group, where type replacement may occur more rapidly. In total, 8022 serum samples from the population-based Finnish Maternity Cohort were retrieved. HPV types 16/18 showed decreased seroprevalence among the unvaccinated in communities only after gender-neutral vaccination (PR16/18A = 0.8, 95% CI 0.7-0.9). HPV6/11 and HPV73 were decreased after gender-neutral vaccination (PR6/11A = 0.8, 95% CI 0.7-0.9, PR73A = 0.7, 95% CI 0.6-0.9, respectively) and girls-only vaccination (PR6/11B = 0.8, 95% CI 0.7-0.9, PR73B = 0.9, 95% CI 0.8-1.0). HPV68 alone was increased but only after girls-only vaccination (PR68B = 1.3, 95% CI 1.0-1.7, PRcore68B = 2.8, 95% CI 1.2-6.3). A large-scale, long-term follow-up found no type replacement in the communities with the strongest reduction of vaccine HPV types. Limited evidence for an increase in HPV68 was restricted to girls-only vaccinated communities and may have been due to secular trends (ClinicalTrials.gov number: NCT00534638).

Background Human papillomavirus (HPV) vaccination of girls with very high (>90%) coverage has the potential to eradicate oncogenic HPVs, but such high coverage is hard to achieve. However, the herd effect (HE) depends both on the HPV type and the vaccination strategy. Methods We randomized 33 Finnish communities into gender-neutral HPV16/18 vaccination, girls-only HPV16/18 vaccination, and hepatitis B virus vaccination arms. In 2007–2010, 11 662 of 20 513 of 40 852 of 39 420 resident boys/girls from 1992 to 1995 birth cohorts consented. In 2010–2014, cervicovaginal samples from vaccinated and unvaccinated girls at age 18.5 years were typed for HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68. Vaccine efficacy for vaccinated girls, HE for unvaccinated girls, and the protective effectiveness (PE) for all girls were estimated. We extended the community-randomized trial results about vaccination strategy with mathematical modeling to assess HPV eradication. Results The HE and PE estimates in the 1995 birth cohort for HPV18/31/33 were significant in the gender-neutral arm and 150% and 40% stronger than in the girls-only arm. Concordantly, HPV18/31/33 eradication was already predicted in adolescents/young adults in 20 years with 75% coverage of gender-neutral vaccination. With the 75% coverage, eventual HPV16 eradication was also predicted, but only with the gender-neutral strategy. Conclusions Gender-neutral vaccination is superior for eradication of oncogenic HPVs.

The gut microbiome has a fundamental role in human health and disease. However, studying the complex structure and function of the gut microbiome using next generation sequencing is challenging and prone to reproducibility problems. Here, we obtained cross-sectional colon biopsies and faecal samples from nine participants in our COLSCREEN study and sequenced them in high coverage using Illumina pair-end shotgun (for faecal samples) and IonTorrent 16S (for paired feces and colon biopsies) technologies. The metagenomes consisted of between 47 and 92 million reads per sample and the targeted sequencing covered more than 300 k reads per sample across seven hypervariable regions of the 16S gene. Our data is freely available and coupled with code for the presented metagenomic analysis using up-to-date bioinformatics algorithms. These results will add up to the informed insights into designing comprehensive microbiome analysis and also provide data for further testing for unambiguous gut microbiome analysis., Measurement(s)genome •rRNA_16STechnology Type(s)DNA sequencingFactor Type(s)sex •age •Smoking •Weight •Height •Diet •MedicationSample Characteristic - OrganismHomo sapiensSample Characteristic - Environmentfeces •colon Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.11902236

Efficacy of human papillomavirus (HPV) vaccines promises to control HPV infections. However, HPV vaccination programs may lay bare an ecological niche for non-vaccine HPV types. We evaluated type-replacement by HPV type and vaccination strategy in a community-randomized trial executed in HPV vaccination naive population. Thirty-three communities were randomized to gender-neutral vaccination with AS04-adjuvanted HPV16/18 vaccine (Arm A), HPV vaccination of girls and hepatitis B-virus (HBV) vaccination of boys (Arm B) and gender-neutral HBV vaccination (Arm C). Resident 1992-95 born boys (40,852) and girls (39,420) were invited. 11,662 boys and 20,513 girls were vaccinated with 20–30% and 45–48% coverage, respectively. HPV typing of 11,396 cervicovaginal samples was performed by high throughput PCR. Prevalence ratios (PR) between arms and ranked order of HPV types and odds ratio (OR) for having multiple HPV types in HPV16 or 18/45 positive individuals were calculated. The ranked order of HPV types did not significantly differ between arms or birth cohorts. For the non-HPV vaccinated 1992–1993 birth cohorts increased PR, between the gender-neutral intervention versus control arms for HPV39 (PRA 1.84, 95% CI 1.12–3.02) and HPV51 (PRA 1.56, 95% CI 1.11–2.19) were observed. In the gender-neutral arm, increased clustering between HPV39 and the vaccine-covered HPV types 16 or 18/45 (ORA16 = 5.1, ORA18/45 = 11.4) was observed in the non-HPV vaccinated 1994–1995 birth cohorts. Comparable clustering was seen between HPV51 and HPV16 or HPV18/45 (ORB16 = 4.7, ORB18/45 = 4.3), in the girls-only arm. In conclusion, definitively consistent postvaccination patterns of HPV type-replacement were not observed. Future occurrence of HPV39 and HPV51 warrant investigation.

Healthcare workers (HCWs) are a risk group for SARS-CoV-2 infection, but which healthcare work that conveys risk and to what extent such risk can be prevented is not clear. Starting on April 24th, 2020, all employees at work (n=15,300) at the Karolinska University Hospital, Stockholm, Sweden were invited and 92% consented to participate in a SARS-CoV-2 cohort study. Complete SARS-CoV-2 serology was available for n=12,928 employees and seroprevalences were analyzed by age, sex, profession, patient contact, and hospital department. Relative risks were estimated to examine the association between type of hospital department as a proxy for different working environment exposure and risk for seropositivity, adjusting for age, sex, sampling week, and profession. Wards that were primarily responsible for COVID-19 patients were at increased risk (adjusted OR 1.95 (95% CI 1.65-2.32) with the notable exception of the infectious diseases and intensive care units (adjusted OR 0.86 (95% CI 0.66-1.13)), that were not at increased risk despite being highly exposed. Several units with similar types of work varied greatly in seroprevalences. Among the professions examined, nurse assistants had the highest risk (adjusted OR 1.62 (95% CI 1.38-1.90)). Although healthcare workers, in particular nurse assistants, who attend to COVID-19 patients are a risk group for SARS-CoV-2 infection, several units caring for COVID-19 patients had no excess risk. Large variations in seroprevalences among similar units suggest that healthcare work-related risk of SARS-CoV-2 infection may be preventable.

The gut microbiome has a fundamental role in human health and disease. However, studying the complex structure and function of the gut microbiome using next generation sequencing is challenging and prone to reproducibility problems due to the heterogeneity of sample sets. Here, we obtained cross-sectional colon biopsies and faecal samples from nine participants in our COLSCREEN study and sequenced them in high coverage using Illumina pair-end shotgun (for faecal samples) and IonTorrent 16S (for paired feces and colon biopsies) technologies. The metagenomes consisted of between 47 and 92 million reads per sample and the targeted sequencing covered more than 300K reads per sample across seven hypervariable regions of the 16S gene. Our data is freely available and coupled with code for the presented metagenomic analysis using up-to-date bioinformatics algorithms. These results will add up to the informed insights into designing comprehensive microbiome analysis and also provide data for further testing for unambiguous gut microbiome analysis.

[Background] Population demography and gene flow among African groups, as well as the putative archaic introgression of ancient hominins, have been poorly explored at the genome level., [Results] Here, we examine 15 African populations covering all major continental linguistic groups, ecosystems, and lifestyles within Africa through analysis of whole-genome sequence data of 21 individuals sequenced at deep coverage. We observe a remarkable correlation among genetic diversity and geographic distance, with the hunter-gatherer groups being more genetically differentiated and having larger effective population sizes throughout most modern-human history. Admixture signals are found between neighbor populations from both hunter-gatherer and agriculturalists groups, whereas North African individuals are closely related to Eurasian populations. Regarding archaic gene flow, we test six complex demographic models that consider recent admixture as well as archaic introgression. We identify the fingerprint of an archaic introgression event in the sub-Saharan populations included in the models (~ 4.0% in Khoisan, ~ 4.3% in Mbuti Pygmies, and ~ 5.8% in Mandenka) from an early divergent and currently extinct ghost modern human lineage., [Conclusion] The present study represents an in-depth genomic analysis of a Pan African set of individuals, which emphasizes their complex relationships and demographic history at population level., This study was funded by the Spanish MINECO grants CGL-2013-44351-P, CGL-2016-75389-P, and the “Unidad de Excelencia Maria de Maeztu” MDM2014-0370. BLG was supported with a Beatriu de Pinós (BP-DGR 2014) fellowship. O.L. was supported by a Ramón y Cajal grant from the Spanish Ministerio de Economia y Competitividad (MEIC) with reference RYC-2013-14797, a BFU2015-68759-P (MEIC/FEDER) grant and the support of Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 937). O.L. also acknowledges the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership; Centro de Excelencia Severo Ochoa; CERCA Programme / Generalitat de Catalunya; the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) through the Instituto de Salud Carlos III; Generalitat de Catalunya through Departament de Salut and Departament d’Empresa i Coneixement; the co-financing by the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) with funds from the European Regional Development Fund (ERDF) corresponding to the 2014-2020 Smart Growth Operating Program. GSV was supported by a FI (2017FI_B2 00010) scholarship. LFKK was supported by an FPI fellowship associated with BFU2014-55090-P (MINECO/FEDER, UE). VNP was financially supported by the Ministry of Health, Government of Catalonia [grant SLT002/16/00496] and a grant from Otto A. Malmi Foundation (Finland). TMB is supported by BFU2017-86471-P (MINECO/FEDER, UE), U01 MH106874 grant, Howard Hughes International Early Career, Obra Social >La Caixa> and Secretaria d’Universitats i Recerca and CERCA Programme del Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880).

Oncogenic non-vaccine human papillomavirus (HPV) types may conceivably fill the vacated ecological niche of the vaccine types. The likelihood of this may differ by the risk of acquiring HPV infections. We examined occurrence of HPV types among vaccinated and unvaccinated subgroups of 1992-1994 birth cohorts with differing acquisition risks up to 9 years post-implementation of HPV vaccination in 33 Finnish communities randomized to: Arm A (gender-neutral HPV16/18 vaccination), Arm B (girls-only HPV16/18 vaccination and hepatitis B-virus (HBV) vaccination of boys), and Arm C (gender-neutral HBV vaccination). Out of 1992-1994 born resident boys (31,117) and girls (30,139), 8,618 boys and 15,615 girls were vaccinated, respectively, with 20-30% and 50% coverage in 2007-2009. In 2010-2013, 8,868 HPV16/18 and non-HPV vaccinated females, and in 2014-2016, 5,574 originally or later (2010-2013) HPV16/18 vaccinated females attended two cervical sampling visits, aged 18.5 and 22-years. The samples were typed for HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68 using PCR followed by MALDI-TOF MS. HPV prevalence ratios (PR) between Arms A/B vs. C were calculated for Chlamydia trachomatis positives (core-group), and negatives (general population minus core group). At both visits the vaccine-protected HPV type PRs did not significantly differ between the core-group and non-core group. Among the vaccinated 18-year-olds, HPV51 occurrence was overall somewhat increased (PRcore = 1.4, PRnon-core. = 1.4) whereas the HPV52 occurrence was increased in the core-group only (PRcore = 2.5, PRnon-core = 0.8). Among the non-HPV vaccinated 18-year-olds, the HPV51/52 PRs were higher in the core-group (PRcore = 3.8/1.8, PRnon-core = 1.2/1.1). The 22-year-olds yielded no corresponding observations. Monitoring of the sexual risk-taking core-group may detect early tendencies for HPV type replacement.

International audience; Coinfections by multiple Human Papillomaviruses (HPVs) are observed in approximately 6-8% of invasive cervical cancer (ICC) cases worldwide. But neither the presence of persistent HPVs coinfections nor their etiological role in the development of ICC is well understood. Cervical HPVs coinfections have been observed randomly, mostly in women with preneoplastic lesions, and only few studies have globally analyzed ICC cases. Here we explored the HPVs multiple infection patterns in a large worldwide sample of cross-sectional ICC cases. Paraffin-embedded ICC biopsy samples were tested using stringent HPV genotyping. Logistic regression models were used to identify the most likely pairwise HPV types in multiple infections. Multivariate analysis was applied to detect significant HPV coinfection patterns beyond pairwise HPVs comparison. Among 8780 HPV DNA-positive ICC cases worldwide, 6.7% (N = 587) contained multiple HPVs. Pairwise analysis revealed that HPV16|74, HPV31|33, HPV31|44, HPV33|44 and HPV45|70 pairs were significantly more frequently found together in multiple infections compared to any other HPV type combination, which supports the occasional role of Alpha-10 LR-HPVs in cervical cancers. In contrast, HPV16|31, HPV16|45, HPV16|51 and HPV18|HPV45 pairs were significantly less frequently found together than with any other HPV pair combination. Multivariate analysis sustained the results and revealed for the first time a distinct coinfection pattern in African ICCs stemming from the clustering of oncogenic HPV51/35/18/52 coinfections in African women. We suggest that the differential geographic HPVs coinfections clustering observed might be compatible with a specific modulation of the natural history/oncogenic potential of particular HPVs multiple infections and warrant monitoring for post-vaccinated.

Background: Very high coverage human papillomavirus (HPV) vaccination of girls has the potential to eradicate some HPV types but low coverage vaccination does not. The protection of unvaccinated individuals by herd effect (HE) varies by HPV type and vaccination strategy. By combining community-randomized trial data and mathematical modeling we show that gender-neutral vaccination is superior for achieving eradication of oncogenic HPVs. Methods: We randomized 33 communities into gender-neutral HPV16/18 vaccination (A), HPV16/18 vaccination of girls only (B), and hepatitis B-virus vaccination of boys and girls (C). From 2007-2010 11,622/40,852 resident boys and 20,513/39,420 resident girls born 1992-1995 consented to the study. At follow-up in 2010-14, cervicovaginal samples from vaccinated and unvaccinated girls were typed for HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68. Trial-based vaccine efficacy (VE) and HE, estimated among non-HPV vaccinated arm A/B girls using arm C controls, were weighted for mean protective effectiveness (PE) estimation, and used for modeling eradication. Findings The HPV18/31/33 HE and PE were significant in younger birth cohorts: four years post vaccination HE and PE were 150% and 40% stronger in the gender-neutral than in the girls-only arm. HPV18/31/33 have moderate to fast clearance rates enabling eradication, and corresponding HEs from vaccinated to unvaccinated arose rapidly. HPV18/31/33 eradication in adolescents/young adults is predicted in 20 years with 75% coverage of gender-neutral vaccination, eradication of HPV16 is predicted within 30 years. Interpretation While low coverage with a girls-only vaccination strategy leaves most females unprotected, HPV-disease eradication of oncogenic HPVs is certain with moderate coverage gender-neutral vaccination strategy. Funding: This ancillary study was partially funded by Academy of Finland, Finnish Cancer Organizations and EU FP7 networks PREHDICT and CoheaHR. GlaxoSmithKline Biologicals SA funded the primary study HPV-040 (NCT00534638, data to be published in a separate manuscript) but was not involved in the conduct of this ancillary study. GlaxoSmithKline Biologicals SA was provided the opportunity to review this manuscript for accuracy of primary HPV-040 data but the authors are solely responsible for final content and interpretation. V.N.P. was supported by a personal grant from the Ministry of Health, Government of Catalonia (PERIS SLT002/16/00496). Declaration of Interest: D.A., J.D., G.G., M.L. and J.P. have received grants from Merck & Co. Inc. or the GSK group of companies through their employers [Family Federation Finland (DA), Karolinska Institute (J.D., M.L.), Universities of Tampere (M.L.) or Helsinki (J.P.) or Imperial College London (G.G.)] for HPV vaccination studies. G.D. is currently a full time employee of Takeda Vaccines, but was working for GSK Biologicals at the time the study was planned and conducted. He holds several patents in the HPV field which have been assigned to the GSK groups of companies and has stock shares in both the GSK groups of companies and Takeda. Ethical Approval: The HPV-040 study (Eudra-CT-2007-001731-55, NCT00534638), and parallel ancillary studies on Chlamydia trachomatis screening (Dnro 111/2009) and HPV screening (ETL-code 13149, NCT02149030) were approved by Finnish ethical committees of the Pirkanmaa and PohjoisPohjanmaa hospital districts in 2007, 2009 and 2013, respectively.

Background: Human papillomavirus (HPV) basic reproductive numbers are low, except for HPV type 16. Thus, vaccination can induce herd effects to reduce the prevalence of many HPV types, especially if gender-neutral vaccination strategy and a vaccine with broad protection against HPV types are used. Methods: We used a cluster-randomized trial implemented in 2007-2009 among early, 1992-1995 born adolescents to create differential herd effects in 11 communities with gender-neutral (Arm A), and 11 communities with girls-only (Arm B) HPV16/18 vaccination achieving 20% coverage in Arm A boys and 45% coverage in Arm A and Arm B girls. In 11 control communities, devoid of any opportunistic HPV vaccination, hepatitis B-virus vaccination covered 30% of boys and 50% of girls. Seroprevalence was assessed for 17 HPV types in consecutive calendar-time (2005-07, 2008-10, 2011-13, 2014-16) strata comprising unvaccinated adolescent and young adult females, who were respectively 19 years or younger, and 20 to 22 years of age at the time of serum sampling. Sexual risk-taking behaviour core-group was defined by herpes simplex virus type-2 antibody positivity. From observed data probabilistic networks and simulated equal size seroprevalence datasets (N=100,000) were also derived. Findings: Following gender-neutral vaccination significant HPV16/18 herd effects were rapidly detected in the adolescent core-group of the gender-neutral vaccination Arm A. HPV51 prevalence tended to increase later in the post-vaccination era (2014-16) among adolescent core-group girls-only vaccination Arm B, as also supported by the simulations. Interpretation: Low to moderate coverage HPV vaccination induces a strong herd effect against HPV16/18 infection reducing circulation of vaccine-targeted HPV types following gender-neutral vaccination. The ecological niche vacated is not immediately filled. Funding Statement: This study was partially funded by Academy of Finland, Finnish Cancer Organizations and EU FP7 networks PREHDICT and CoheaHR. GlaxoSmithKline Biologicals SA funded the community randomized HPV-040 trial (NCT00534638), (data to be published in a separate manuscript) however was not in any way involved in the conduct of this study. This study received some support via a personal grant from the Ministry of Health, Government of Catalonia (PERIS SLT002/16/00496).The study was supported by grants from the Swedish Cancer Society (CAN 2015/399 and CAN 2017/459), from the Swedish Foundation for Strategic Research (grant number RB13-0011) and from Karolinska Institutet (Dnr. 2018-01523). ML received funding from KI to his Professorship (Dnr. 2-3698/2017). Declaration of Interests: JD and ML have received grants from Merck & Co. Inc and the GSK group of companies through their employers the Karolinska Institute (both JD and ML), or the University of Tampere (ML) for conducting HPV vaccination studies. Ethics Approval Statement: The community randomized study obtained permissions from the Ethical Review Board of Pirkanmaa Hospital District (R07113M 14.6.2007) and the Ethical Review Board of North Bothnia Hospital District (EETTMK:111/2009). Informed consent to use the FMC serum samples for research purposes is granted by the pregnant women when they donate their 1st trimester sample for screening of congenital infections.

Analysis of pathogen genome data sequenced from clinical and historical samples has made it possible to perform phylogenetic analyses of sexually transmitted infections on a global scale, and to estimate the diversity, distribution, and coevolutionary host relationships of these pathogens, providing insights into pathogen emergence and disease prevention. Deep-sequenced pathogen genomes from clinical studies and ancient samples yield estimates of within-host and between-host evolutionary rates and provide data on changes in pathogen genomic stability and evolutionary responses. Here we examine three groups of pathogens transmitted mainly through sexual contact between modern humans to provide insight into ancient human behavior and history with their pathogens. Exploring ancient pathogen genomic divergence and the ancient viral-host parallel evolutionary histories will help us to reconstruct the origin of present-day geographical distribution and diversity of clinical pathogen infections, and will hopefully allow us to foresee possible environmentally induced pathogen evolutionary responses. Lastly, we emphasize that ancient pathogen DNA research should be combined with modern clinical pathogen data, and be equitable and provide advantages for all researchers worldwide, e.g., through shared data.

Efficacy of human papillomavirus (HPV) vaccines promises to control HPV infections. However, HPV vaccination programs may lay bare an ecological niche for non-vaccine HPV types. We evaluated type-replacement by HPV type and vaccination strategy in a community-randomized trial executed in HPV vaccination naïve population. Thirty-three communities were randomized to gender-neutral vaccination with AS04-adjuvanted HPV16/18 vaccine (Arm A), HPV vaccination of girls and hepatitis B-virus (HBV) vaccination of boys (Arm B) and gender-neutral HBV vaccination (Arm C). Resident 1992-95 born boys (40,852) and girls (39,420) were invited. 11,662 boys and 20,513 girls were vaccinated with 20-30% and 45-48% coverage, respectively. HPV typing of 11,396 cervicovaginal samples was performed by high throughput PCR. Prevalence ratios (PR) between arms and ranked order of HPV types and odds ratio (OR) for having multiple HPV types in HPV16 or 18/45 positive individuals were calculated. The ranked order of HPV types did not significantly differ between arms or birth cohorts. For the non-HPV vaccinated 1992-1993 birth cohorts increased PR, between the gender-neutral intervention versus control arms for HPV39 (PR

Background Human papillomavirus (HPV)-related anal cancer lesions are often found adjacent to the squamocolumnar junction (SCJ). We have assessed the histopathology and associated HPV genotypes in anal SCJ lesions in surgically excised anal warts in HIV-negative and –positive patients. Methods Histopathology identified 47 squamous intraepithelial lesions (SILs) adjacent to the SCJ amongst a total of 145 cases of clinically diagnosed anal condylomata. The anal SCJ lesions were further analyzed with p16, CK7 and p63 immunohistochemistry and HPV genotyping. Results Sixteen (16/47) of the excised anal wart lesions contained HSIL; Three were HSIL and exclusively associated with oncogenic HPVs. A further thirteen (13/47) were mixed lesions. Of these eight were HSILs with LSIL and six were HSILs with papillary immature metaplasia (PIM); Ten of the mixed lesions were associated with one or more oncogenic HPVs, while three cases were exclusively associated with HPV6. Conclusions Clinically diagnosed anal warts cannot be assumed to be limited to low-grade lesions as anal warts of the SCJ often show heterogeneous lesions, with coexistence of LSIL, PIM, and HSIL. Lesions showing PIM, however, may mimic HSIL, because they are hypercellular, but lack the nuclear atypia and conspicuous mitotic activity of HSIL; and are p16 negative., Highlights • Anal warts of the SCJ are often heterogeneous; with LSIL, including PIM and HSIL. • Anal HSILs only with HPV6 may indicate that LR-HPVs have some role in oncogenesis. • Recognition of PIM is important given its potential for being confused with HSIL. • Clinical diagnosis of anal warts cannot be assumed to be limited to LSIL. • Microscopic examination of anal warts is encouraged with appropriate immunostains.

International audience; Every human suffers through life a number of papillomaviruses (PVs) infections, most of them asymptomatic. A notable exception are persistent infections by Human papillomavirus 16 (HPV16), the most oncogenic infectious agent for humans and responsible for most infection-driven anogenital cancers. Oncogenic potential is not homogeneous among HPV16 lineages, and genetic variation within HPV16 exhibits some geographic structure. However, an in-depth analysis of the HPV16 evolutionary history was still wanting. We have analyzed extant HPV16 diversity and compared the evolutionary and phylogeographical patterns of humans and of HPV16. We show that codivergence with modern humans explains at most 30% of the present viral geographical distribution. The most explanatory scenario suggests that ancestral HPV16 already infected ancestral human populations and that viral lineages co-diverged with the hosts in parallel with the split between archaic Neanderthal-Denisovans and ancestral modern human populations, generating the ancestral HPV16A and HPV16BCD viral lineages, respectively. We propose that after out-of-Africa migration of modern human ancestors, sexual transmission between human populations introduced HPV16A into modern human ancestor populations. We hypothesize that differential coevolution of HPV16 lineages with different but closely related ancestral human populations and subsequent host-switch events in parallel with introgression of archaic alleles into the genomes of modern human ancestors may be largely responsible for the present-day differential prevalence and association with cancers for HPV16 variants.

Genital warts (GWs) and laryngeal papillomatosis (LP) are two usually benign pathologies related to infection with human papillomaviruses (HPVs), mainly HPV6 and HPV11. The aim of this work was to describe the genetic diversity of HPV6 and HPV11 isolates found in GWs and LPs, and to analyse the differential involvement of viral variants in either lesion. A total of 231 samples diagnosed as GWs (

Human papillomavirus (HPV)16 is the most oncogenic human papillomavirus, responsible for most papillomavirus-inducedanogenital cancers. We have explored by sequencing and phylogenetic analysis the viral variant lineages presentin 692 HPV16-monoinfected invasive anogenital cancers from Europe, Asia,and Central/South America. We have assessed the contribution of geography and anatomy to the differential prevalence of HPV16 variants and to the nonsynonymous E6 T350G polymorphism. Most (68%) of the variance in the distributionof HPV16 variants was accounted for by the differential abundance of the different viral lineages. The most prevalent variant (above 70% prevalence) in all regions and in all locations was HPV16_A1-3,except in Asia, whereHPV16_A4 predominated in anal cancers. The differential prevalence of variants as a function of geographical origin explained 9% of the variance, and the differential prevalence of variants as a function of anatomical location accountedfor less than 3% of the variance. Despite containing similar repertoires of HPV16 variants, we confirm the worldwide trend of cervical cancers being diagnosed significantly earlier than other anogenital cancers (early fifties vs. early sixties).Frequencies for alleles in the HPV16 E6 T350G polymorphism were similar across anogenital cancers from the same geographical origin. Interestingly, anogenita lcancers from Central/South America displayed higher 350G allele frequencies also within HPV16_A1-3 lineage compared with Europe. Our results demonstrate ample variation in HPV16 variants prevalence in anogenital cancers, which is partly explained by the geographical origin of the sample and only marginally explained by the anatomical location of the lesion, suggesting that tissue specialization is not essential evolutionary forces shaping HPV16 diversity in anogenital cancers. Fil: Nicolás Párraga, Sara. Instituto Catalán de Oncología; España Fil: Gandini, Carolina Lia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; Argentina. Instituto Catalán de Oncología; España Fil: Pimenoff, Ville N.. Instituto Catalán de Oncología; España Fil: Alemany, Laia. Instituto Catalán de Oncología; España Fil: de Sanjosé, Silvia. Instituto Catalán de Oncología; España Fil: Bosch, F. Xavier. Instituto Catalán de Oncología; España Fil: Bravo, Ignacio G.. Centre National de la Recherche Scientifique. Institut de Recherche Pour Le Developpement. Departement Societes Et Sante. Laboratorio de Genetique Et Evolution Des Maladies Infectieuses; Francia

Northwest Siberia is geographically remote territory, which has been settled by indigenous human populations probably since the Upper Paleolithic. To investigate the genetic landscape of Northwest Siberians, we have analyzed mitochondrial and Y chromosome DNA polymorphisms of 169 unrelated individuals from Khanty and Mansi ethnic groups in Northwest Siberia. In addition, HVS-I sequences (N = 3522) and Y chromosome SNP data (N = 2175), obtained from the literature, were used to elucidate the genetic relationships among the North Eurasian populations. The results show clinal distributions of mtDNA and Y chromosome haplogroups along East-West axis of Northern Eurasia. In this context, the Ugric-speaking Khanty and Mansi appear as unique intermediate populations carrying Upper Paleolithic and more recent haplotypes typical for both West and East Eurasian gene pools. This admixture indicates that the Khanty and Mansi populations have resided in the contact zone of genetically distinguishable eastern and western Eurasia.

We have analyzed the two hypervariable regions HVS-I and HVS-II of 200 Finnish male individuals for forensic purposes. The distribution of the haplotypes within Finland was determined by the geographical knowledge of the donors' maternal ancestors. In our population sample, we identified 135 different mtDNA haplotypes. Different mtDNA sequences were further divided to haplogroups using the EMPOP software. The most common haplogroups were H (40.0%) and U (27.5%). Subgroup U5b, which contains earlier described "Saami motif", consisted majority (65.5%) of the sample in the U haplogroup. Analysis of the mtDNA sequence hypervariable regions I and II showed that the mtDNA diversity within the Finnish population sample was comparable to other European populations and uniformly distributed. This is contrary to the Y-STR "minimal haplotype" diversity, which in Finland is lower than in any of the other European populations studied so far.

A single-nucleotide variant, C/T(-13910), located 14 kb upstream of the lactase gene (LCT), has been shown to be completely correlated with lactase persistence (LP) in northern Europeans. Here, we analyzed the background of the alleles carrying the critical variant in 1,611 DNA samples from 37 populations. Our data show that the T(-13910) variant is found on two different, highly divergent haplotype backgrounds in the global populations. The first is the most common LP haplotype (LP H98) present in all populations analyzed, whereas the others (LP H8-H12), which originate from the same ancestral allelic haplotype, are found in geographically restricted populations living west of the Urals and north of the Caucasus. The global distribution pattern of LP T(-13910) H98 supports the Caucasian origin of this allele. Age estimates based on different mathematical models show that the common LP T(-13910) H98 allele (approximately 5,000-12,000 years old) is relatively older than the other geographically restricted LP alleles (approximately 1,400-3,000 years old). Our data about global allelic haplotypes of the lactose-tolerance variant imply that the T(-13910) allele has been independently introduced more than once and that there is a still-ongoing process of convergent evolution of the LP alleles in humans.

[OBJECTIVE] Linkage disequilibrium (LD) and recombination rate variations are known to vary considerably between human genome regions and populations mostly because of the combined effects of mutation, recombination, and demographic history. Thus, the pattern of LD is a key issue to disentangle variants associated with complex traits. Here, we aim to describe the haplotype structure and LD variation at the pharmacogenetically relevant cytochrome P450 CYP2C and CYP2D gene regions among European populations. [METHODS] To assess the haplotype structure, LD pattern, and recombination rate variations in the clinically significant CYP2C and CYP2D regions, we genotyped 143 single-nucleotide polymorphisms (SNPs) across these two genome regions in a diverse set of 11 European population samples and one sub-Saharan African sample. [RESULTS] Our results showed extended patterns of LD and in general a low rate of recombination at these loci, and a low degree of allele differentiation for the two cytochrome P450 regions among Europeans, with the exception of the Sami and the Finns as European outliers. The Sami sample showed reduced haplotype diversity and higher LD for the two cytochrome P450 regions than the other Europeans, a feature that is proposed to enhance the LD mapping of underlying common complex traits. However, recombination hotspots and LD blocks at these two regions showed highly consistent structures across Europeans including Finns and Sami. Moreover, we showed that the CEPH sample has significantly higher tag transferability among Europeans and a more efficient tagging of both the rare CYP2C9 and the common CYP2C19 functional variants than the Sami. Our data set included CYP2C9*3 (rs1057910) and CYP2C19*2 (rs4244285) enzyme activity-altering variants associated in a recent genome-wide study with acenocoumarol-induced and warfarin-induced anticoagulation or to the antiplatelet effect of clopidogrel, respectively. Including these known activity-altering variants, we showed the haplotype variation and high derived allele frequencies of novel recently identified acenocoumarol genome-wide associated SNPs at CYP2C9 (rs4086116) and CYP2C18 (rs12772169, rs1998591, rs2104543, rs1042194) loci in a comprehensive set of 11 European populations. Furthermore, a significant frequency difference of a CYP2C19*2 gene mutation causing variable drug reactions was observed among Europeans. [CONCLUSION] The CEPH sample representing the general European population as such in the HapMap project seems to be the optimal population sample for the LD mapping of common complex traits among Europeans. Nevertheless, it is still argued that the unique pattern of LD in the Sami may offer an advantage for further association mapping, especially if multiple rare variants play a role in disease etiology. However, besides the activity-altering CYP2C9*3 (rs1057910) and CYP2C19*2 (rs4244285) variants, the high derived allele frequencies of novel recently identified acenocoumarol genome-wide associated SNPs at CYP2C9 (rs4086116) and CYP2C18 (rs12772169, rs1998591, rs2104543, rs1042194) loci variants indicated that the CYP2C region may have been influenced by selection. Thus, this fine-scale haplotype map of the CYP2C and CYP2D regions may help to choose markers for further association mapping of complex pharmacogenetic traits at these loci. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Anal condylomata are common in HIV-positive individuals and among men who have sex with men (MSM). Generally attributable to infection by low-risk human papillomaviruses (HPVs), condylomata are considered benign low-grade squamous intraepithelial lesions (SILs). However, anal condylomata have occasionally been linked to high-grade SIL and to oncogenic, high-risk HPVs. Here we describe the range of intraepithelial lesions and of the associated HPVs in heterosexual men and women and MSM. Perianal and anal condylomata were collected from 243 patients (56 heterosexual women, 61 heterosexual men and 126 MSM, including 41 HIV-positive MSM). We assessed lesion histology and HPV genotype. Prevalence estimates and Poisson models were used. Irrespective of HIV infection status, MSM showed a higher proportion of condylomata as high-grade SILs compared to heterosexual men/women. High-grade SILs were also more prevalent in anal than in perianal lesions in all patient groups. HIV-positive MSM exhibited increased prevalence ratio (4.6; 95% confidence interval 2.1–10.0) of perianal low-grade SILs containing only high-risk HPVs compared to HIV-negative MSM. In addition, more than 64% of anal SILs with a high-grade component, regardless of HIV infection, were exclusively associated with low-risk HPVs. In anal condylomata, both high-grade and low-grade SILs can be associated with high-risk and/or low-risk HPVs. Particularly, low-grade perianal SILs associated with high-risk HPVs were common in HIV-positive MSM, while presence of only low-risk HPVs in high-grade SILs were common in both MSM groups. Our findings sound a note of caution for the common clinical practice for the treatment of anal condylomata as benign lesions in MSM and HIV-positive patients.

We analysed samples of 400 Finnish males using nine Y-chromosomal short tandem repeat (STR) loci (minimal haplotype); for 200 of these subjects an additional seven Y-chromosomal STR loci were used. The geographical distribution of the observed haplotypes was determined from 200 individuals of known paternal origin within Finland. The observed number of alleles varied from 2 to 13 alleles per locus. A total of 146 minimal haplotypes were identified in our population sample. Interestingly, 90 (22.5%) individuals shared an identical haplotype. This haplotype was extremely frequent in the northern and eastern subpopulations of Savo, Pohjanmaa and Karjala (53, 42 and 37%, respectively). With the seven additional loci analysed in the sample of 200 individuals, 120 haplotypes were identified, and individuals sharing the most common haplotype decreased to 13.0%. However, in comparison to other European populations, the Finnish population showed decreased genetic diversity (GD) when the number of different minimal haplotypes in the population was divided by the sample size (36.5% in Finns versus 83.7% on average). Our results strongly support the earlier hypothesis of individual isolated Y-chromosomal lineages and population substructuring in Finland. For paternity testing, power of exclusion was 92% using minimal haplotype data, but including the seven additional loci this value increased to 97%.

In order to assess the utility of mtDNA typing for forensic purposes in Uruguay, a population sample of 120 maternally unrelated individuals were amplified and directly sequenced for the HV1 and for the HV2 segments in the control region of the human mtDNA, following previous international recommendations (1).