HPV16 variants distribution in invasive cancers of the cervix, vulva, vagina, penis, and anus

Human papillomavirus (HPV) 16 is the most oncogenic human papillomavirus, responsible for most papillomavirus-induced anogenital cancers. We have explored by sequencing and phylogenetic analysis the viral variant lineages present in 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 non-synonymous E6 T350G polymorphism. Most (68%) of the variance in the distribution of 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, where HPV16_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 accounted for 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, anogenital cancers 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

Using population biobanks to understand complex traits, rare diseases, and their shared genetic architecture

The study of the role of genetic variability in common traits has led to a growing number of studies aimed at representing whole populations. These studies gather multiple layers of information on healthy and non-healthy individuals at large scales, constituting what is known as population biobanks.In this thesis I took advantage of the potential of these population biobanks to measure the influence of genetic variation in common and rare traits. I explored the mechanisms behind these by exploring their interaction with conditions, physiological measurements, and habits in general and healthy population. First, I used the Lifelines cohort, with genetic information of Dutch population. Here, my colleagues and I explored traits with different levels of genetic influence we uncovered associations between both Blood type and dairy consumption with human gut microbiome function and composition, and we identified a protective factor for a rare type of cardiomyopathy with potential use for diagnosis.Additionally, within a global collaboration across world-wide biobanks totaling > 2 million individuals, we demonstrated the robustness of the connections between genetic variation and 14 different diseases across the populations. We also provided methodological guidance for the combination of the effects of genetic variation to calculate the risk of disease in studies including biobanks with populations of different ethnic backgrounds.Overall, my PhD research contributed on identifying and validating which factors are relevant for potential clinical applications, and provided guidelines to be used in future genetic studies on common traits and diseases at a global scale

Variabilidad genética del virus del papiloma humano tipos 16, 58 y 52 en mujeres chachi y afroecuatorianas en el norte del Ecuador

Human Papillomavirus (HPV) is the most common sexually transmitted virus worldwide and its presence is directly associated with a high risk of developing cervix, anus, vagina, vulva, penis and oropharyngeal cancer. The present work is the first Ecuadorian study in which a molecular analysis of the MY09/MY11 region was carried out to find the lineages, possible sublineages and simple nucleotide polymorphisms (SNPs) of HPV genotypes 16, 58 and 52 in Chachi and Afro-Ecuadorian women from the north coast of the country, using 47 samples of cervical scrapes...El Virus del Papiloma Humano (VPH) es el virus de transmisión sexual más común en todo el mundo y su presencia está directamente asociada con un alto riesgo de desarrollar cáncer de cérvix, ano, vagina, vulva, pene y orofaringe. El presente trabajo es el primer estudio del Ecuador en el que se realizó un análisis molecular de la región MY09/MY11 para encontrar los linajes, posibles sublinajes y polimorfismos de nucleótido simple (SNPs) de los genotipos VPH16, 58 y 52 en mujeres de etnia Chachi y afroecuatoriana de la costa norte del país, empleando 47 muestras de raspados cervicales. Un 30% de las 47 muestras mostraron amplificación positiva para el gen L1 de VPH y un 21% para los genotipos de interés..