Human Papillomavirus 16 (HPV16) causes 70% of invasive cervical cancers (ICC) worldwide. Interaction between HPV16 genetic diversity, host genetics and target tissue largely determine the chances to ...trigger carcinogenesis. We have analyzed the differential prevalence of viral variants in 233 HPV16‐monoinfected squamous (SCC), glandular (ADC) and mixed (ADSC) ICCs from four continents, assessing the contribution of geographical origin and cancer histology. We have further quantified the contribution of viral variants and cancer histology to differences in age at tumor diagnosis. The model fitted to the data explained 97% of the total variance: the largest explanatory factors were differential abundance among HPV16 variants (78%) and their interaction with cancer histology (9.2%) and geography (10.1%). HPV16_A1‐3 variants were more prevalent in SCC while HPV16_D variants were increased in glandular ICCs. We confirm further a non‐random geographical structure of the viral variants distribution. ADCs were diagnosed at younger ages than SCCs, independently of the viral variant triggering carcinogenesis. HPV16 variants are differentially associated with histological ICCs types, and ADCs are systematically diagnosed in younger women. Our results have implications for the implementation of cervical cancer screening algorithms, to ensure proper early detection of elusive ADCs.
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Interaction between Human Papillomavirus 16 genetic diversity, host genetics and target tissue largely determines the odds of HPV16 triggering invasive cervical cancers (ICCs), but the mechanisms remain unclear. Our study assessed HPV16 variant diversity in three ICC histological types in European, Central‐South American, Asian and African samples. Different viral variants displayed different prevalence depending on geographical origin and histological cancer type. Genuine differences in HPV16 lineage prevalence explained more than 70% of all variance in the viral lineage distribution, with the interaction of geographical origin and histological cancer type with HPV16 variants together accounting for 20% of the data variance.
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 (<n = 198) or LP (<n = 33) and caused by HPV6 or HPV11 monoinfections were analysed. The phylogenetic relationships of the retrieved viral sequences were explored. We have identified the long control region and the intergenic E2–L2 region as the two most variable regions in both HPV6 and HPV11 genomes. We have generated new HPV6 (<n = 166) or HPV11 (<n = 65) partial sequences from GWs and LPs lesions spanning both regions and studied them in the context of all available sequences of both types (final n = 412). Our results show a significant (p <0.01) differential presence of HPV6 variants among both pathologies, with HPV6 B variants being preferentially found in GW versus LP samples. No differential involvement of HPV11 variants was observed. Our findings suggest that different HPV6 variants may either show differential tropism or have different potential to induce lesions in different epithelia.
Quality of the nucleic acids extracted from Formalin Fixed Paraffin Embedded (FFPE) samples largely depends on pre-analytic, fixation and storage conditions. We assessed the differential sensitivity ...of viral and human double stranded DNA (dsDNA) to degradation with storage time.
We randomly selected forty-four HPV16-positive invasive cervical cancer (ICC) FFPE samples collected between 1930 and 1935 and between 2000 and 2004. We evaluated through qPCR the amplification within the same sample of two targets of the HPV16 L1 gene (69 bp, 134 bp) compared with two targets of the human tubulin-β gene (65 bp, 149 bp).
Both viral and human, short and long targets were amplified from all samples stored for 15 years. In samples archived for 85 years, we observed a significant decrease in the ability to amplify longer targets and this difference was larger in human than in viral DNA: longer fragments were nine times (CI 95% 2.6-35.2) less likely to be recovered from human DNA compared with 1.6 times (CI 95% 1.1-2.2) for viral DNA.
We conclude that human and viral DNA show a differential decay kinetics in FFPE samples. The faster degradation of human DNA should be considered when assessing viral DNA prevalence in long stored samples, as HPV DNA detection remains a key biomarker of viral-associated transformation.
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 nonsynonymous 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.
We communicate a comprehensive description of human papillomavirus (HPV)16 variants in anogenital cancers in Europe, Central/South America, and Asia and quantify the contributions of anatomy and geography. Prevalence values of HPV16 variants are largely the same independently of the geographical origin and anatomical location of the lesion, with the only exception of anal cancers in Asia. Geographic dispersal with humans and tissue adaptation are not major driving forces in the evolution of HPV16, the most oncogenic HPV.
Dois experimentos foram conduzidos com o objetivo de avaliar o uso do farelo de algodão na alimentação de coelhos em crescimento. No ensaio de digestibilidade, foram utilizados oito coelhos de ambos ...os sexos, com 50 dias de idade, da raça Nova Zelândia Branca. O período experimental constou de oito dias de adaptação às condições experimentais e quatro dias de coleta total de fezes. O farelo de algodão foi fornecido como único alimento, adicionando-se 0,5% de cloreto de sódio e 0,4% de mistura mineral vitamínico, e, em seguida,umedecido com 40% de água formando uma pasta. Os coeficientes de digestibilidade aparente foram de 66,81; 84,65; 41,14; 39,00 e 68,27% para matéria seca, proteína bruta, fibra em detergente neutro, fibra em detergente ácido e energia bruta, respectivamente. No experimentode desempenho, foram utilizados 32 coelhos (16 machos e 16 fêmeas) da raça Nova Zelândia Branca, com 41 dias de idade, alojados individualmente e distribuídos em delineamento inteiramente casualizado em quatro tratamentos (quatro níveis de substituição da proteína bruta do farelo de soja pela proteína bruta do farelo de algodão: 0; 33; 66 e 100%) e oito repetições. Ao final do experimento (76 dias de idade), os animais foram abatidos para avaliação de carcaça. Observou-se aumento (p < 0,05) no consumo diário de ração e na conversão alimentar, porém o ganho de peso médio e as características de carcaça não foram afetados, sugerindo que o farelo de algodão (38% PB) pode substituir totalmente o farelo de soja em ração de coelhos em crescimento, subentendendo seu uso na dependência da oferta e preço de mercado.Two experiments were carried out aiming to evaluate the use of cottonseed meal as feed for growing rabbits. Eight White New Zealand rabbits, 50 days old, male and female, were used in the digestibility trial. The experimental period lasted for 12 days (8 days of adaptation and 4 days of whole faeces collection). Cottonseed meal was offered as the only food source, with the addition of 0.5% NaCl and 0.4% vitamin mineral mixture. The cottonseed meal was then moisted with 40% water, forming a paste. The apparent digestibility coefficients were: 66.81; 84.65; 41.14; 39.00 and 68.27% for dry matter, crude protein, neutral detergent fiber, acid detergent fiber and gross energy, respectively. In the performance trial, 32 White New Zealand rabbits (16 males and 16 females), 41 days old, were used and kept in individual cages. Data was analyzed under a randomized design with eight replications and four treatments (four levels ofcrude protein replacement of soybean meal by cottonseed meal crude protein: 0; 33; 66 and 100%). At the end of the experiment, the rabbits (76 days old) were finished for carcass evaluation. An increase was observed (p < 0.05) in daily feed intake and feed/gain ratio, but there was no significant effect on average live weight gain and carcass quality. The results show that cottonseed meal can totally replace soybean meal as feed for growing rabbits, depending only on economic factors, such as the ever-changing prices for each type of feed.
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