human papillomavirus HPV

HPV Can Damage Genes and Chromosomes Directly, Whole-Genome Sequencing Study Shows

Press release from the James Cancer Center COLUMBUS, Ohio – The virus that causes cervical, head and neck, anal and other cancers can damage chromosomes and genes where it inserts its DNA into human DNA, according to a new study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James). It’s long been known that cancer-causing types of human papillomavirus (HPV) produce two viral proteins, called E6 and E7, which are essential for the development of cancer. However, they are not sufficient to cause cancer. Additional alterations in host-cell genes are necessary for cancer to develop. Here, scientists identified a new mechanism by which HPV may damage host DNA directly and contribute to cancer development. Published in the journal Genome Research, this laboratory study used whole-genome sequencing to investigate the relationship between the HPV and host genomes in human cancers. “Our sequencing data showed in vivid detail that HPV can damage host-cell genes and chromosomes at sites of viral insertion,” says co-senior author David Symer, MD, PhD, assistant professor of molecular virology, immunology and medical genetics at the OSUCCC – James. “HPV can act like a tornado hitting the genome, disrupting and rearranging nearby host-cell genes,” Symer explains. “This can lead to overexpression of cancer-causing genes in some cases, or it can disrupt protective tumor-suppressor genes in others. Both kinds of damage likely promote the development of cancer.” “We observed fragments of the [...]

Charlotte Parker2013-11-08T12:21:37-07:00November, 2013|OCF In The News, Oral Cancer News|

Merck’s Experimental HPV Vaccine Shows Promise in Late Stage Trial

Source: Nasdaq By: Peter Loftus Published: November 3, 2013 An experimental Merck & Co. vaccine appeared to provide broader protection against a cancer-causing virus than the company's Gardasil shot in clinical trials. Merck said the study results support its plan to submit the new vaccine, code-named V503, for U.S. regulatory approval by year's end, which could lead to market launch next year at the soonest. Merck expects health-care providers to eventually switch to V503 if the product receives marketing approval. Some analysts expect its annual sales could exceed $1 billion. "The case for using V503 is even stronger than the case for using Gardasil, which was already strong," said Roger Perlmutter, head of Merck's research and development unit. Dr. Perlmutter has singled out V503 as one of the programs Merck will focus on as it overhauls its R&D unit in a bid to recover from a series of setbacks. Gardasil, launched in 2006, was the first vaccine to protect against human papillomavirus, or HPV, a sexually transmitted virus that can cause cervical cancer in women and other less-common types of cancer in males and females. The U.S. Centers for Disease Control and Prevention recommends HPV vaccination of boys and girls ages 11 and 12, though it is approved to be given to people ages 9 to 26. GlaxoSmithKline also sells an HPV vaccine called Cervarix. Gardasil is designed to protect against four strains of HPV, two of which are believed to be responsible for about 70% of all cervical [...]

Charlotte Parker2013-11-05T11:13:34-07:00November, 2013|Oral Cancer News|

Prominent M.D. Anderson cancer doctor dies at 63

Source: Houston ChroniclePublished: June 22,2013By: Todd Ackerman OCF sadly reports the death of one of its founding board members and good friend, Dr. Kian Ang. Dr. Ang was Brian Hill's personal radiation oncologist when he was treated at MDACC for his oral cancer. The two developed a strong friendship over the years. Brian often refers to Dr. Ang as one of his most valued mentors in the treatment of oral cancers, and in critical thinking when reviewing scientific papers. He will be greatly missed as a strong contributor and advisor to OCF, having helped set its direction for many years. Dr. Kian Ang, a prominent cancer doctor who helped popularize the M.D. Anderson Cancer Center tradition of ringing a bell at the end of radiation treatment, died Wednesday. He was 63. Ang, who pioneered practice-changing treatment for head and neck cancers, succumbed to cancer at M.D. Anderson, surrounded by family. He was diagnosed recently with the disease. "Dr. Ang was the true triple threat - outstanding clinician, accomplished investigator and educator par excellence," said Dr. Randal Weber, chairman of head and neck surgery at M.D. Anderson. "He was the guy who could do it all, what many of us aspire to be but fall short of." Colleagues at the University of Texas cancer center said Ang's greatest achievements included pioneering work treating head and neck cancers with a combination of radiation and chemotherapy, particularly targeted therapies; and determining that cancers of the throat are more sensitive to treatment if caused by the [...]

Charlotte Parker2013-09-27T11:06:22-07:00September, 2013|Oral Cancer News|

Concerned About HPV-Related Cancer Rise, Researchers Advocate Boosting HPV Vaccination Rates

By: Anna AzvolinskySource: JNCI Journal of the National Cancer Institute Advance AccessPublished: August 29, 2013 Deaths from the major cancers—lung, colorectal, breast, and prostate—continue to decline, a trend that started in the early 1990s. Cancer incidence is also declining, if slightly, for both sexes. That’s the good news from the annual Report to the Nation on the Status of Cancer, a joint research effort by the American Cancer Society, the Centers for Disease Control and Prevention, the National Cancer Institute, and the North American Association of Central Cancer Registries (J Natl. Cancer Inst. 2013;105:175–201). But the study also shows an uptick in rates of anal and oropharyngeal cancer, a type of head and neck cancer related to infection with the human papillomavirus (HPV), in the 10-year period ending in 2009. Cancer of the oropharynx increased among white men and women (3.9% and 1.7%, respectively). Anal cancer also increased in both sexes, with the greatest increase among black men (5.6%) and white women (3.7%). Rates of vulvar cancer, another HPV-related cancer, also increased among women despite continued lower rates of cervical cancer. Researchers attribute this rise in HPV related cancers to more HPV infections. “We think that increases in oral–genital sexual practices and increasing number of sexual partners that occurred some 30 years ago as part of the sexual revolution may be implicated in part of the increase in cancer rates we are seeing today,” said Edgar P. Simard, Ph.D., M.P.H., senior epidemiologist of surveillance research. Although rates of HPV infection from three decades ago were not available in the joint report, a trend exists of men and women now in their 50s and 60s having the highest rates of both oropharyngeal and anal cancers. To directly relate HPV infection [...]

Charlotte Parker2013-09-03T14:10:57-07:00September, 2013|Oral Cancer News|

Enhanced Radiation Sensitivity in HPV-Positive Head and Neck Cancer

Source: American Association for Cancer Research Received February 28, 2013.Revision received April 9, 2013.Accepted April 26, 2013. Abstract Patients with human papillomavirus (HPV+)–associated head and neck cancer (HNC) show significantly improved survival outcome compared with those with HPV-negative (HPV−) tumors. Published data examining this difference offers conflicting results to date. We systematically investigated the radiation sensitivity of all available validated HPV+ HNC cell lines and a series of HPV− HNC cell lines using in vitro and in vivo techniques. HPV+ HNCs exhibited greater intrinsic radiation sensitivity (average SF2 HPV−: 0.59 vs. HPV+: 0.22; P < 0.0001), corresponding with a prolonged G2–M cell-cycle arrest and increased apoptosis following radiation exposure (percent change 0% vs. 85%; P = 0.002). A genome-wide microarray was used to compare gene expression 24 hours following radiation between HPV+ and HPV− cell lines. Multiple genes in TP53 pathway were upregulated in HPV+ cells (Z score 4.90), including a 4.6-fold increase in TP53 (P < 0.0001). Using immortalized human tonsillar epithelial (HTE) cells, increased radiation sensitivity was seen in cell expressing HPV-16 E6 despite the effect of E6 to degrade p53. This suggested that low levels of normally functioning p53 in HPV+ HNC cells could be activated by radiation, leading to cell death. Consistent with this, more complete knockdown of TP53 by siRNA resulted in radiation resistance. These results provide clear evidence, and a supporting mechanism, for increased radiation sensitivity in HPV+ HNC relative to HPV− HNC. This issue is under active investigation in a series of clinical trials attempting [...]

Charlotte Parker2013-08-01T13:59:40-07:00August, 2013|Oral Cancer News|

Leaders in Dentistry: Dr. Ezra Cohen

Source: Dr. Bicuspid By: Donna Domino, Features Editor Date: July 17, 2013 May 21, 2013 — DrBicuspid.com is pleased to present the next installment of Leaders in Dentistry, a series of interviews with researchers, practitioners, and opinion leaders who are influencing the practice of dentistry. We spoke with Ezra Cohen, MD, an associate professor of medicine and the co-director of the head and neck cancer program at the University of Chicago, and the associate director for education at the university’s Comprehensive Cancer Center. Dr. Cohen specializes in head and neck, thyroid, and salivary gland cancers, and is an expert in novel cancer therapies who has conducted extensive research in molecularly targeted agents in the treatment of these cancers. His research interests include discovering how cancers become resistant to existing treatments and overcoming these mechanisms and ways to combine radiotherapy with novel agents. Here Dr. Cohen discusses trends in the incidence, detection, and treatment of oral and head and neck cancers. DrBicuspid.com: What’s the significance of your recent finding that there may be five distinct subgroups of the human papillomavirus (HPV)? Dr. Cohen: The purpose of the research was trying to define molecular subgroups of head and neck cancer (HNC) to inform therapy and outcomes a lot more than we do now as defined by stage and anatomic site. We were taking advantage of a cohort of patients that we treated in a similar fashion at the University of Chicago with a chemotherapy regimen that we commonly use here. The patients [...]

Webmaster2013-07-19T07:48:02-07:00July, 2013|Oral Cancer News|

Reasons for Not Vaccinating Adolescents: National Immunization Survey of Teens, 2008–2010

Source: PediatricsAuthors: Paul M. Darden, MD, David M. Thompson, PhD, James R. Roberts, MD, MPH, Jessica J. Hale, MSa, Charlene Pope, PhD, MPH, RN, Monique Naifeh, MD, MPHa, and Robert M. Jacobson, MDPublished Online: March 18, 2013 Abstract OBJECTIVE: To determine the reasons adolescents are not vaccinated for specific vaccines and how these reasons have changed over time. METHODS: We analyzed the 2008–2010 National Immunization Survey of Teens examining reasons parents do not have their teens immunized. Parents whose teens were not up to date (Not-UTD) for Tdap/Td and MCV4 were asked the main reason they were not vaccinated. Parents of female teens Not-UTD for human papillomavirus vaccine (HPV) were asked their intent to give HPV, and those unlikely to get HPV were asked the main reason why not. RESULTS: The most frequent reasons for not vaccinating were the same for Tdap/Td and MCV4, including “Not recommended” and “Not needed or not necessary.” For HPV, the most frequent reasons included those for the other vaccines as well as 4 others, including “Not sexually active” and “Safety concerns/Side effects.” “Safety concerns/Side effects” increased from 4.5% in 2008 to 7.7% in 2009 to 16.4% in 2010 and, in 2010, approaching the most common reason “Not Needed or Not Necessary” at 17.4% (95% CI: 15.7–19.1). Although parents report that health care professionals increasingly recommend all vaccines, including HPV, the intent to not vaccinate for HPV increased from 39.8% in 2008 to 43.9% in 2010 (OR for trend 1.08, 95% CI: 1.04–1.13). CONCLUSIONS: Despite doctors increasingly recommending adolescent vaccines, parents [...]

Charlotte Parker2013-06-20T10:42:12-07:00June, 2013|Oral Cancer News|

NIH scientists find promising biomarker for predicting HPV-related oropharynx cancer

Source: National Cancer InstitutePublished: 6-17-13 Researchers have found that antibodies against the human papillomavirus (HPV) may help identify individuals who are at greatly increased risk of HPV-related cancer of the oropharynx, which is a portion of the throat that contains the tonsils. In their study, at least 1 in 3 individuals with oropharyngeal cancer had antibodies to HPV, compared to fewer than 1 in 100 individuals without cancer. When present, these antibodies were detectable many years before the onset of disease. These findings raise the possibility that a blood test might one day be used to identify patients with this type of cancer. Genomic structure of HPV The results of this study, carried out by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health, in collaboration with the International Agency for Research on Cancer (IARC), were published online June 17, 2013, in the Journal of Clinical Oncology. Historically, the majority of oropharyngeal cancers could be explained by tobacco use and alcohol consumption rather than HPV infection. However, incidence of this malignancy is increasing in many parts of the world, especially in the United States and Europe, because of increased infection with HPV type 16 (HPV16). In the United States it is estimated that more than 60 percent of current cases of oropharyngeal cancer are due to HPV16. Persistent infection with HPV16 induces cellular changes that lead to cancer. HPV E6 is one of the viral genes that contribute to tumor formation. Previous [...]

Charlotte Parker2013-06-18T12:16:01-07:00June, 2013|Oral Cancer News|

Enhanced radiation sensitivity in HPV-positive head and neck cancer

Source: http://cancerres.aacrjournals.orgAuthors: Randall J. Kimple1,*,Molly A. Smith1,Grace C Blitzer1,Alexandra D Torres1,Joshua A Martin1,Robert Z. Yang1,Chimera R Peet1,Laurel D. Lorenz2,Kwangok P Nickel3,Aloysius J Klingelhutz4,Paul F Lambert5, andPaul M Harari1 Abstract Patients with human papillomavirus associated (HPV+) head and neck cancer (HNC) demonstrate significantly improved survival outcome compared to those with HPV-negative (HPV-) tumors. Published data examining this difference offers conflicting results to date. We systematically investigated the radiation sensitivity of all available validated HPV+ HNC cell lines and a series of HPV- HNC cell lines using in vitro and in vivo techniques. HPV+ HNCs exhibited greater intrinsic radiation sensitivity (average SF2 HPV- 0.59 vs. HPV+ 0.22, p<0.0001), corresponding with a prolonged G2/M cell cycle arrest and increased apoptosis following radiation exposure (percent change 0% vs. 85%, p=0.002). A genome-wide microarray was used to compare gene-expression 24 hours following radiation between HPV+ and HPV- cell lines. Multiple genes in TP53 pathway were upregulated in HPV+ cells (Z score 4.90), including a 4.6 fold increase in TP53 (p<0.0001). Using immortalized human tonsillar epithelial cells, increased radiation sensitivity was seen in cell expressing HPV-16 E6 despite the effect of E6 to degrade p53. This suggested that low levels of normally functioning p53 in HPV+ HNC cells could be activated by radiation, leading to cell death. Consistent with this, more complete knockdown of TP53 by siRNA resulted in radiation resistance. These results provide clear evidence, and a supporting mechanism, for increased radiation sensitivity in HPV+ HNC relative to HPV- HNC. This issue is under active investigation in [...]

Charlotte Parker2013-06-10T16:15:32-07:00June, 2013|Oral Cancer News|

The Man’s Guide to HPV

Source: Men's HealthBy: Melaina Juntti What men can do about HPV Michael Douglas caught major flak for saying oral sex gave him throat cancer. But if you're laughing, it's time to grow up. Oral cancers caused by the sexually transmitted human papillomavirus (HPV) have skyrocketed 225 percent in the past 15 years, with men accounting for 75 percent of all cases. The number-one culprit: HPV passed via oral sex. It used to be that cigarettes caused most of these cancers. But since smoking rates have plummeted over the past few decades, and we're having way more oral sex today than even our fathers' generation, HPV has become the most common STD in the U.S. – inevitably leading to more oral cancer cases. It only takes one time going down on someone to contract HPV, and experts estimate that 80 percent of us will be exposed to the virus at some point in our lives. This STD sometimes causes genital warts, but according to the Centers for Disease Control and Prevention, that's not very common. In most cases, HPV has no symptoms. And since no test exists to detect HPV in guys, you won't know you have the virus until years later – if it turns into cancer. "It's very hard to determine when you acquired HPV," says Dr. William Schaffner, chairman of the Department of Preventive Medicine at Vanderbilt University. "It doesn't usually come from just one sexual episode. That said, every once in a while, cancer develops within [...]

Charlotte Parker2013-06-10T11:35:49-07:00June, 2013|OCF In The News|