Findings may help physicians tailor cervical cancer therapies to specific gene mutations and improve the accuracy of diagnostic screening tests for this disease
New scientific knowledge about the role of human papillomavirus (HPV) in the growth of cervical cancer is creating excitement within the medical community. Among other things, these findings could encourage more widespread vaccination against HPV. That in turn would lead to reduced Pap smear testing by pathology laboratories over time.
For these reasons, cytopathologists and cytotechnologists will be particularly interested in the research findings that were published as a first-ever, international genomic study of cervical cancer, which was published online December 25, 2013, at Nature.com. Researchers discovered that the location where HPV integrates itself into the human genome, is where it causes amplified gene expression that promotes and elevates mutated gene activity that may cause cervical cancer to develop.
Benefits of International Research Collaboration
Cooperation of researchers from the United States, Mexico, and Norway was essential to the study’s relevance worldwide, suggested Helga Salvesen, M.D., Ph.D., who was co-senior author of the Nature article. She is a Professor of Clinical Medicine at University of Bergen in Norway, and was a visiting scientist at the Boston-based Broad Institute during the study. “By analyzing genomic data from diverse populations, we can discover patterns to disease progression in context of the full range of human genetic variation,” she stated.
In a unique investigation into the role of HPV in causing cervical cancer, co-senior study author Helga Salvesen, M.D., Ph.D., (pictured) a Professor of Clinical Medicine at University of Bergen, Norway, noted that findings of this study—particularly the role of ERBB2 in cervical cancer—provide a unique and comprehensive new tool to guide clinical trial design for future studies of this disease. (Photo copyright Centre for Molecular Medicine Norway.)
Study Discovers How HPV May Trigger Cancer Growth
To discover the genetic underpinnings of the disease, study investigators sequenced and examined the exomes−the protein-producing region of the human genome−of 115 cervical cancer patients from Norway and Mexico. In some cases, whole genomes were sequenced to help focus on gene expression.
Researchers then compared genomic data from cervical cancer tumors with healthy tissue from the same individual to determine what had gone wrong, or muted, noted a press release from the Dana-Farber Cancer Institute.
“Our findings further elucidate the key role HPV is playing in the development of cervical cancer, which in turn emphasizes the importance of combatting the disease by vaccinating against HPV,” remarked Matthew Meyerson, M.D., Ph.D., co-senior author of the study. He is a Professor of Pathology and Medical Oncology at the Boston-based Dana-Farber Cancer Institute and a Senior Associate at the Broad Institute.
Matthew Meyerson, M.D., Ph.D. (pictured), is co-senior author of the study and a Professor of Pathology and Medical Oncology at the Boston-based Dana-Farber Cancer Institute and a Senior Associate at the Broad Institute. He noted that the study of HPV’s role in causing cervical cancer confirmed the importance of preventing cervical cancer with vaccination. (Photo copyright Dana-Farber Cancer Institute.)
Researchers Identify Potential New Targets for Drug Therapy
The research team also identified new possible targets for drug therapy by revealing 13 somatic gene mutations considered significant in cervical cancer. Eight of these mutations had not been previously associated with cervical cancer. Two other mutations had never been linked with any form of cancer.
One of the most notable of these mutations not previously linked to cervical cancer is ERBB2, also known as Her-2. The mutation was found in a small but significant subset of the tumors, noted the press release. This finding suggests that patients with this gene mutation, which is a known oncogene in breast cancer, may benefit from ERBB2 inhibitors already approved by the FDA.
Another novel gene mutation identified by the researchers is in MAPK1. MAPK1 is involved in the MAP kinase signaling pathway, a network of interconnected genes that help to control cell growth regulation, explained the Dana-Farber press release. Mutations of other genes in this pathway are known to drive cancer, but this is the first time MAPK1 has been found to be mutated, presenting the possibility of another kinase signal pathway target for drug therapy.
HPV May Disrupt the Immune System
There was one more major finding. It was the prevalence of mutations in genes that affect the immune system. Researchers said this suggests that disruptions to the immune system may play a more important role in cancer progression than scientists previously believed.
“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,” noted Salveson. “The present study−in particular the findings related to ERBBE−thus represents a unique and comprehensive new tool to guide clinical trial design in the future.”
“The outstanding findings our successful collaborative international research are giving us, here in Mexico, very powerful arguments in favor of the benefit of speeding up the adoption of molecular methods for screening HPV,” noted co-author Hugo Barrera, Ph.D.. “[This can be] followed by colposcopy to detect cancer at its earliest phases when it is curable.” Barrera is a Professor of Biochemistry and Molecular Medicine at the School of Medicine and University Hospital of the University of Nuevo Leon in Monterey, Mexico.
Significance of Findings for Pathologists and Medical Laboratories
There currently are about 80 different known HPV mutations, of which 15 are found in about 80% of cervical cancers. But existing clinical laboratory tests for HPV are designed to look for only 10 to 12 of those mutations. Therefore, today’s generation of HPV screening tests do not detect all mutations involved in cervical cancer.
The new knowledge provided by this study is expected to be useful in developing improved diagnostic tests for HPV. It may also open the door to targeted therapies that attack a patient’s specific cervical cancer mutations. This would be a first in treatment for cervical cancer and provide an opportunity for pathologists to create a new class of companion diagnostic tests that can be offered by medical laboratories.
—by Patricia Kirk
Related Information:
International team completes systematic, genomic study of cervical cancer
