Protein Inhibitor May Bring a Topical Treatment for HPV

/PRNewswire/ -- Human papillomavirus (HPV) causes cervical cancer, the second most common cause of cancer death for women, and is a common cause of anogenital and some head and neck cancers. Thanks to research being done at Tufts University School of Medicine, patients infected with cancer-causing HPV may someday have an alternative to surgical and harsh chemical treatments. In a study funded by the National Institutes of Health and published online in advance of print in The FASEB Journal, the researchers report on the development of a protein-based inhibitor that could provide a topical treatment for HPV.

"Currently, there is no cure for HPV, and the available treatment options involve destroying the affected tissue. We have developed a protein inhibitor that blocks HPV protein expression in cell culture, a first step toward a topically-applied treatment for this cancer-causing virus," said senior author James Baleja, Ph.D., associate professor of biochemistry at Tufts University School of Medicine (TUSM) and member of the biochemistry program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts.

"Vaccines are helping to lower the incidence of HPV, but vaccines will not help the millions of women and men who currently have an infection, especially those who have high-risk and persistent infections. Social and economic challenges make widespread administration of a vaccine difficult, particularly in developing countries. A topical treatment for HPV could provide an economical option," he continued.

HPV affects approximately 20 million people in the United States, making it the most common sexually transmitted infection. There are more than 100 types of HPV of which more than 40 are sexually transmitted. These include two high-risk types, HPV-16 and HPV-18, which cause the majority of cervical and anogenital cancers, and some portion of head and neck cancers, particularly oral cavity and oropharynx cancers. Cervical cancer is diagnosed in nearly 500,000 women each year, killing 250,000 annually. In the United States, it was estimated that 12,000 women in 2010 would be diagnosed with cervical cancer, while 10,100 women and men in the United States get vulvar, vaginal, penile or anal cancers each year. In addition, some portion of the head and neck cancers in the United States (11,300 men and women each year) is attributable to HPV. Other types of HPV, or low-risk HPV, can cause genital warts or are infections that clear on their own.

In their efforts to inhibit HPV, Baleja and his team zeroed in on the viral protein E2, which controls viral activities including DNA replication and the activation of cancer-causing genes. Using structure-guided design, the team developed a protein called E2R that prevents E2 from functioning normally. When the researchers applied E2R to a cell model of HPV biology, viral gene transcription was halted. Because HPV infects epithelial cells, the outermost layer of the skin and the mucous membranes, protein inhibitors such as E2R could be applied in a topical form.

Baleja and colleagues used biophysical tools including circular dichroism spectroscopy and x-ray crystallography to test the structure and stability of different inhibitors. The most stable inhibitor was then tested in mammalian cells and was found to inhibit the E2 protein of HPV-16, the high-risk strain that is most commonly associated with cancers. The data in this study suggest that the inhibitor may also be effective against another high-risk virus, HPV-18, as well as a low-risk virus, HPV-6a, which causes warts.

Additional authors on the paper are first author Kakoli Bose, Ph.D., formerly a postdoctoral fellow in the Baleja laboratory at TUSM and now with the Advanced Centre for Treatment, Research and Education in Cancer at the Tata Memorial Center in India; Gretchen Meinke, Ph.D., senior research associate in the Bohm Laboratory at TUSM, and Andrew Bohm, associate professor in the Department of Biochemistry at TUSM and member of the biochemistry program faculty at the Sackler School of Graduate Biomedical Sciences.

This research was funded by the National Cancer Institute, part of the National Institutes of Health, and by the Lifespan/Tufts/Brown Center for AIDS Research (CFAR), a joint research effort between Tufts and Brown Universities and their affiliated hospitals and centers. CFAR is funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

Bose K, Meinke G, Bohm A, and Baleja J. The FASEB Journal. "Design and characterization of an enhanced repressor of human papillomavirus E2 protein." Published online April 11, 2011. DOI 10.1096/fj.10-176461

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PIEDMONT HOSPITAL URGES GEORGIA WOMEN TO GET SCREENED

In 2007, the American Cancer Society estimated there were 11,000 cases of cervical cancer diagnosed in the United States. While cervical cancer is at a four percent decrease overall, thousands of women are still dying as a result of it each year. January is Cervical Cancer Awareness and Screening Month and Piedmont Hospital is encouraging women throughout Georgia to get cervical cancer screenings.

The primary reason for the decline in the incidence and mortality rate of women with cervical cancer is due to the widespread use of the Papanicolaou (Pap) test to detect cervical abnormalities. A Pap test can detect cervical cancer before it spreads or even develops – dramatically improving the odds of surviving the disease, and it is the most important thing women can do to protect themselves from cervical cancer.

“Regular screenings for women are the first defense against cervical cancer,” said Alfred Jenkins, M.D., OBGYN at Piedmont Gynecology Oncology. "If more women were screened regularly, many unnecessary deaths from cervical cancer could be avoided."

The American Cancer Society recommends two ways to prevent cancer: Avoid the risk factors for pre-cancers, such as HPV, and get a regular Pap test. The Pap test can even detect HPV infection and pre-cancers. Treatment of these problems can stop cervical cancer before it develops fully into an invasive cancer.

“Since January is Cervical Cancer Awareness and Screening Month, it is the perfect time to encourage women to see their doctor to get screened for cervical cancer,” Dr. Jenkins said. “I also encourage them to ask their doctor about the HPV vaccine as another method to prevent cervical cancer.”

Dr. Jenkins has been a part of the Piedmont Healthcare family since early last year, working with Piedmont Gynecologic Oncology located on the Piedmont Hospital campus. He also holds part-time office hours at Piedmont Fayette Hospital in Fayetteville. Dr. Jenkins is board-certified in obstetrics and gynecology and gynecologic oncology. Prior to joining Piedmont Gynecologic Oncology, Dr. Jenkins served as director of the Division of Gynecologic Oncology at M.D. Anderson Cancer Center-Orlando. While there, he performed the first gynecologic robotics procedure in the state of Florida. He also performs fertility-sparing surgery for cervical cancer.