New Cervical Cancer Analysis Offers Clues On Role Of HPV

A multi-national effort to analyze the genome of cervical cancer has yielded some exciting discoveries that may inform future therapy.

Researchers, publishing in the journal Nature, identified 13 genetic mutations that can now be considered significant for cervical cancer. Of those, two of the mutations had never before been linked to cancer. And eight had been linked to other cancers, but not previously cervical -- including one uncovered mutation to the gene ERBB2 (also known as Her-2), which has been previously connected to breast cancer and, as such, targeted gene therapies already exist for patients with this mutation.

"This suggests that a subset of cervical cancer patients could be candidates for clinical trials involving ERBB2 inhibitors, which are available and FDA-approved," explained Akinyemi Ojesina, a co-first author of the paper and a postdoctoral fellow at the Broad Institute and the Dana-Farber Cancer Institute. "It is an exciting finding that could be translatable to the clinic."

Currently, between 10 and 15 percent of all cancer-related deaths in women globally, are a result of cervical cancer. Those rates are particularly high in developing countries where women are likely to have minimal access to early screening efforts, like pap smears, and preventive medicine, like the human papillomavirus (HPV) vaccine.

Researchers also found mutations in the immune system gene HLA-A -- which has been linked to squamous cell lung cancer -- and HLA-B, another immune system gene that helps the body identify foreign invaders. The researchers deduced from this discovery that mutations that affect the immune system may play a bigger role than previously thought in the development of cancer.

"So far, our knowledge regarding genetic alterations as potential targets for therapeutics has been limited, and no targeted therapeutics are yet in routine clinical use," said co-senior author Helga Salvesen, a professor of clinical medicine at University of Bergen, Norway. "The present study -- in particular the findings related to ERBB2 -- thus represents a unique and comprehensive new tool to guide clinical trial design in the future."

To conduct the study, researchers took samples from 115 cervical cancer patients from Norway and Mexico and then conducted exome sequencing on all of them, which is a type of analysis of the genetic code in the protein-coding regions of the genome, known as the exome. On some samples, the researchers performed an entire genomic sequencing and on some, they focused on transcriptome sequencing, which looks at gene expression.

In terms of transcriptome sequencing, the researchers focused on HPV, which is present in all cervical cancers. They looked at the "integration sites" where HPV inserts genetic code into the human genome, finding that HPV inserted itself where expression was "turned up" highest. The researchers concluded from this finding that the virus may have an amplification function, promoting the mutated genes that lead to cancer.

"Our findings further elucidate the key role HPV is playing in the development of cervical cancer, which in turn emphasizes the importance of combating the disease by vaccinating against HPV," Matthew Meyerson, co-senior author and a professor of pathology and medical oncology at Dana-Farber Cancer Institute, said in a statement.

Previous sequencing of HPV strains led to the recent discovery at Ohio State University that HPV damages human DNA and then inserts its own genetic material into the human genome.

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