HPV73 a non-vaccine type causes cervical cancer

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HPV73 a non-vaccine type causes cervical cancer

Quinta, 16.05.2019

Finding a New Viral Cause of Cervical Cancer—Virtually all cases of cervical cancer are caused by high-risk types of human papillomavirus (HPV). In a study published online on April 9 in International Journal of Cancer, Ana Gradissimo, Ph.D., and Robert D. Burk, M.D., provide the first molecular evidence showing that HPV73—now classified as “possibly oncogenic”—definitely can cause cervical cancer. The findings are a matter of public health concern for two key reasons: HPV screening tests aimed at preventing cervical cancer don’t test for HPV73; and since current HPV vaccines don’t include HPV73, they won’t be able to prevent HPV73--related cervical disease. The researchers recommend that the International Agency for Research on Cancer upgrade HVP73’s classification from possibly carcinogenic to carcinogenic and that public health officials monitor of HPV73’s prevalence in cervical cancer across populations. Dr. Burk is professor of pediatrics, of microbiology & immunology, of epidemiology & public health, of obstetrics & gynecology and women’s health, and an attending physician at Montefiore. Dr. Gradissimo is a postdoctoral research fellow at Einstein.


Autores e Afiliações:

Amaro-Filho SM1, Gradissimo A2, Usyk M2, Moreira FCB3, de Almeida LM4, Moreira MAM1, Burk RD2,5.

Genetics Program, National Cancer Institute (INCA), Rio de Janeiro, Brazil.

2 Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY.

3 Pathology Division (DIPAT), National Cancer Institute (INCA), Rio de Janeiro, Brazil.

4 Department of Epidemiology, National Cancer Institute (INCA), Rio de Janeiro, Brazil.

5 Department of Epidemiology and Population Health, Microbiology and Immunology, and Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY.



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.

International Journal of Cancer