HPV73 a nonvaccine type causes cervical cancer.
HPV73 is classified as possibly oncogenic. It is neither routinely evaluated in HPV screening, nor covered by any of the prophylactic vaccines. We sought to investigate the carcinogenic characteristics of HPV73. Molecular studies were performed on eight cervix cancer biopsy specimens containing HPV73 from a cross-sectional cancer cohort of 590 women referred to the National Cancer Institute in Rio de Janeiro, Brazil. Transcriptional activity of HPV73 was evaluated by detection of spliced transcripts of E6/E6* and E1^E4 in cDNA created from RNA isolated from fresh tissue. Disruption of viral E1 and E2 genes in the tumor DNA was assessed by overlapping PCR amplification. Evaluation of viral integration was performed using a customized capture panel and next-generation sequencing, and an in-house bioinformatic pipeline. HPV73 E6/E6* transcripts were found in 7/7 specimens with available RNA, and three also had HPV73 E1^E4 transcripts. Disruption of E1 and E2 genes was observed in 4/8 specimens. Integration of HPV73 sequences into the cancer cell genomes was identified in all cervix cancer tissues. These results provide evidence that HPV73 is an oncogenic virus that can cause invasive cervix cancer. With current molecular screening and HPV vaccination, not all cervix cancers will be prevented.
['Amaro-Filho|Sergio M|SM|', 'Gradissimo|Ana|A|', 'Usyk|Mykhaylo|M|', 'Moreira|Fabio C B|FCB|', 'de Almeida|Liz M|LM|', 'Moreira|Miguel A M|MAM|', 'Burk|Robert D|RD|0000-0002-8376-8458']
D000328:Adult D000368:Aged D001938:Brazil D003430:Cross-Sectional Studies D004273:DNA, Neoplasm D005260:Female D006801:Humans D008875:Middle Aged D009856:Oncogene Proteins, Viral D027383:Papillomaviridae D030361:Papillomavirus Infections D016133:Polymerase Chain Reaction D012367:RNA, Viral D002583:Uterine Cervical Neoplasms D016662:Virus Integration
cervical cancer HPV transcriptionally active integration oncogenic type