RESUMEN
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.
Asunto(s)
Adenocarcinoma/virología , Carcinoma Adenoescamoso/virología , Carcinoma de Células Escamosas/virología , Neoplasias del Cuello Uterino/virología , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Adulto , Anciano , Carcinoma Adenoescamoso/epidemiología , Carcinoma Adenoescamoso/patología , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/patología , Femenino , Genotipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 16/patogenicidad , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/virología , Filogenia , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología , Proteínas Virales/genéticaRESUMEN
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.