Early effect of the HPV vaccination programme on cervical abnormalities in Victoria, Australia: an ecological study

Source: The Lancet



Australia introduced a human papillomavirus (HPV) vaccination programme with the quadrivalent HPV vaccine for all women aged 12—26 years between 2007 and 2009. We analysed trends in cervical abnormalities in women in Victoria, Australia, before and after introduction of the vaccination program.


With data from the Victorian Cervical Cytology Registry between 2003 and 2009, we compared the incidence of histopathologically defined high-grade cervical abnormalities (HGAs, lesions coded as cervical intraepithelial neoplasia of grade 2 or worse or adenocarcinoma in situ; primary outcome) and low-grade cytological abnormalities (LGAs) in five age groups before (Jan 1, 2003, to March 31, 2007) and after (April 1, 2007, to Dec 31, 2009) the vaccination programme began. Binary comparisons between the two periods were done with Fisher’s exact test. Poisson piecewise regression analysis was used to compare incident rate trends.


After the introduction of the vaccination programme, we recorded a decrease in the incidence of HGAs by 0·38% (95% CI 0·61—0·16) in girls younger than 18 years. This decrease was progressive and significantly different to the linear trend in incidence before introduction of the vaccination (incident rate ratio 1·14, 1·00—1·30, p=0·05). No similar temporal decline was recorded for LGAs or in older age groups.


This is the first report of a decrease in incidence of HGAs within 3 years after the implementation of a population-wide HPV vaccination programme. Linkage between vaccination and screening registers is needed to confirm that this ecological observation is attributable to vaccination and to monitor participation in screening among vaccinated women.



Oral Cancer Foundation breaks records in April’s Awareness and Screening Month

Source: MSNBC News
Author: staff

Oral cancer is an insidious disease that too often is not discovered until very late in its development, as it might not produce symptoms the average person may notice. By then treatments are less effective, and because of late discovery in far too many patients, it has a five year survival rate of only about 57%, much lower than cancers we commonly hear about. Oral cancer has existed outside the awareness of much of the public, yet it will take one life, every hour of every day in the U.S. This year the combination of unprecedented efforts by the relatively small, non-profit Oral Cancer Foundation, a coalition of strategic partners they formed, and a dose of celebrity power, created what might be called a perfect storm; and one that potentially will change public awareness of one of the few cancers that is actually increasing in incidence in the U.S.

For thirteen years in a row, April has been oral cancer awareness month nationally. More than 85% of all head and neck cancers are oral and oropharyngeal disease. Historically, a loose coalition of stakeholders in the disease has mustered about 200 screening events in April in facilities ranging from large institutions to individual dental offices around the country. Those participants opened their doors for at least a half-day to opportunistically screen members of the public in their communities for free, to find early stage disease, and to raise public awareness.

This year the Oral Cancer Foundation, which assumed responsibility for the logistics and promotion of the April effort, was able to create nearly 2,000 sites/events, a ten-fold increase over any previous year. In combination with 4 major walk/run awareness events the Foundation coordinated in April, tens of thousands of individual screenings for this deadly disease were conducted.

When speaking of this unprecedented success, Brian Hill, the Executive Director of the Oral Cancer Foundation, who is also a survivor of a late stage 4 oral cancer, stated, “I think that several things impacted our success. As a small organization that routinely deals with limited funding and human resources, we historically build strategic alliances to accomplish our goals. As a result, we had established relationships with large and powerful organizations to tap for help. We have a significant membership base of private practice doctors and clinical institutions that were already in place to actually accomplish the screenings, and the foundation put some of its other agendas on hold during March and April, to apply ourselves fully to the task. Combine those assets with an “A-list” celebrity who has recently come out of treatment for the disease, award-wining actor Michael Douglas, altruistically choosing to use his significant celebrity and visibility to advocate for early detection. His prime time appearances on Oprah, The Today Show and The View, discussing the need for early discovery and asking the American public to get screened for the disease, and you have an optimum environment to be successful.”

Dr. Michael Alfano, Vice Chancellor of NYU, and one of the Oral Cancer Foundation’s advisors, was particularly impressed with the metrics at the end of the month. Dr. Alfano has been an oral cancer advocate for decades, and his insightful development of the Oral Cancer Consortium, a confederacy of allied universities, and medical institutions in NY, NJ, and PA began the April screening efforts in 1998. That group continues to be involved today. “I am very pleased that OCF continues to build on their many positive credits in the world of oral cancer. To see what this idea has now become is highly gratifying. Screening has enormous potential to save lives when applied in an opportunistic manner. When the dental community, which is routinely and daily involved in the oral environment, embraces this issue, they become an important first line of defense against these cancers through early discovery of suspect tissues. OCF’s ability to organize these dental practices, and move them to active participation clearly has made a difference.”

The screenings this April were primarily visual and tactile, though many offices used some adjunctive devices in their efforts. None of these devices like the VELscope which uses a wavelength-specific beam of blue light to identify tissues with abnormalities in the oral cavity, are in any way invasive to the patients. Jamie O’Day, the Treatment Facilities Coordinator for OCF observed, “This particular cancer lends itself well to a screening methodology which is quick, painless, and even outside the realm of April’s free events, very inexpensive to accomplish. It is primarily visual and tactile, with the medical and dental professionals looking for things that a layperson may not notice, since they are often painless. Something as simple as a tissue discoloration, a hard painless lymph node in the neck, or in a patient’s verbal history taking, the statement that when swallowing they feel like something is painlessly stuck in their throat, or swallowing has become more difficult, are just a few of the signs and symptoms that professionals know are red flags. While there are more potential symptoms, I state these to illustrate how someone might easily ignore them, allowing a potentially deadly situation to prosper to a more advanced stage.”

“This is the very reason that an annual exam by a trained professional is so important,” Brian Hill added. “There is no question that annual screening and testing for potentially life threatening diseases has become the norm in the U.S. today. There are legitimate concerns about the financial impacts of some of these screenings, whether private or third party paid, and the invasiveness of them as well. Oral cancer screening is likely the least expensive or invasive cancer screening a person can have. I often joke that it is so simple that in the five-minute procedure you don’t even have to take your clothes off. As to expense, many dental offices conduct this cancer exam just as part of their normal intra and extra oral exam with no additional charges.”

Several of OCF’s partners, which the foundation credits with much of the successful turnout this year, are heavy hitters in the world of dentistry, and included both professional organizations and private sector firms.

Dr. Ross Kerr, chair of the Oral Cancer Task Force of the American Academy of Oral Medicine, said of his organizations involvement, “Oral cancer is on the rise in the U.S.. A new viral etiology, Human Papilloma Virus #16 (HPV16) is bringing a new demographic of individuals to the disease. This is the same virus which is a cause of cervical cancers in women. A decade ago, we were confident that we knew who was at high risk for oral cancers, but today that is significantly less so with this viral component as a cause. Historically those who smoked for decades, or were heavy alcohol consumers, developed these cancers after their fifth decade of life. Today we are seeing young, non-smoking individuals as the fastest growing segment of the oral cancer population. While that historic group still is a concern, this new demographic makes differentiation of those at high risk much more problematic. I think that the foundation’s approach to this through opportunistic screening is particularly important today. We may in the future have biological markers that we could test through salivary diagnostics to isolate those most at risk, but today the conventional screening protocol is the tool that we can immediately apply to the problem with tangible results. We (AAOM) were very pleased to be a partner with the Oral Cancer Foundation this year, and will continue to be involved in their future efforts. They clearly understand and can apply the mechanisms to get results.”

Two other dental professional groups also joined OCF’s efforts: The American Dental Association, and the Academy of General Dentistry. Mr. Hill commented that this commitment from these two powerful dental organizations represented a partnership that he has been working towards for some time. “The April awareness initiative was the tipping point opportunity to formalize a joint effort with these two organizations,” said Hill, “and both provided the outreach we needed to bring on private dental practices as screening sites. AGD provided the foundation with a full-page ad in the March issue of their journal Impact, which reaches the vast majority of all general dentists in the U.S. This contribution helped greatly. The ADA also through their publications, encouraged the dental community to partner with us through targeted stories. I think the partnership was made possible this year by changes inside the ADA, particularly the naming of Dr. Kathleen O’Loughlin to the Executive Director position. She is an individual who brings a significant public health background, combined with her own social consciousness to the organization, and I am optimistic that this is just the beginning of things that we can accomplish together. We could not have reached the significant level of dental participations without them.”

In the private sector, the Foundation sought to expand an existing relationship with the world’s largest dental products distribution company and a Fortune 500 member, Henry Schein Inc. Chairman of the Board and CEO Stanley Bergman created a call to action letter directed at their tens of thousands of US customers, asking them to join the effort with OCF. When combined with the messages that were already on the dental community’s radar, this direct request for their involvement was pivotal. LED Dental Inc. also reached out to thousands of customers who use their oral cancer screening tool, the VELscope, and contributed to the dental outreach as well. Outside the world of dentistry, pharmaceutical giant Bristol Meyers Squibb partially supported the costs of the effort through a dedicated grant given to OCF. “This was our first year working with BMS,” observed Megan Cannon, OCF’s Director of Operations, “and I hope that this huge leap OCF was able to facilitate in public awareness, screening sites, and numbers of individuals screened, will fuel their desire to work with OCF in a bigger way in the future. For all the donated time by screeners and volunteers, there is a significant financial component to doing this annual event well. We could not have grown this awareness month program without that generous financial support.” The balance of the funding that the Foundation needed to accomplish this year’s success came from an unrestricted grant in 2010 from The Entertainment Industry Foundation, a longtime supporter of the Oral Cancer Foundation, through the affiliated Bruce Paltrow Fund. OCF Founder Hill stated, “Many of our most important accomplishments in the last couple of years have only been possible through EIF’s generosity. They have been the strongest of all OCF’s supporters, and valuable allies in the war against cancer. They are the powerhouse behind the highly visible and effective Stand Up 2 Cancer effort, that is a catalyst for breakthrough ideas and collaborations in medicine that have not previously existed. We are proud to be official partners with them in their Stand Up 2 Cancer program, and now with their financial support of our efforts, we have developed a more complex and productive synergy.”

According to Mr. Hill, “This year’s screening and awareness events were a huge success by past standards, and I am very proud of what The Oral Cancer Foundation has accomplished. In fact, the efforts were so successful, that we have extended the events into May, and some offices are even signing up to do events in June. My only regret is that we were asked to take on the April effort so late in the game, with only about 4 weeks to pull things together. I believe that next year, with plenty of time to fine tune what we have learned, drum up additional financial support for the national screening and awareness month, and add new components to the program, that we and our partners will be able to accomplish truly amazing things.”

Oral Cancer is not a rare disease. It kills one person every hour of every day in the U.S., and 100 new individuals will be diagnosed each day with oral cancer. These staggering statistics make these free events crucial, as awareness of the disease and its risk factors in the U.S. population is so low. Oral cancer is the largest group of those cancers which fall into the head and neck cancer category. Common names for it include anatomical sites where it occurs such as mouth cancer, tongue cancer, tonsil cancer, head and neck cancer, and throat cancer. While treatments for it can be effective, survivors are often left with significant quality of life issues, including impaired speech, swallowing dysfunctions, and facial disfigurements from surgeries.

Contact for further information: Brian Hill, Executive Director OCF,  (949)278-4362

Additional information can be found on the Foundation’s web site

The Oral Cancer Foundation is an IRS registered 501c3 non-profit public charity.

American Dental Association encourages public to get screened for oral cancer

Author: press release

The American Dental Association (ADA) and the Oral Cancer Foundation (OCF) encourage people  to take part in Oral Cancer Awareness Month in April by visiting a dentist for a free oral cancer screening.  So far, more than 1,250 sites across the nation have registered their screening events with the OCF.

“Although many dentists perform oral cancer screenings as a routine part of dental examinations, the ADA encourages dentists to go out into their communities during the week of April 11-15 to provide free oral cancer screenings to people who might not regularly visit a dentist,” said ADA Spokesperson Sol Silverman, D.D.S., a professor of oral medicine at the University of California, San Francisco.

“Early detection is critical in increasing survival rates for patients who have developed an oral cancer; and recognizing and managing precancerous lesions is extremely important in prevention,” he said.

Mr. Brian Hill, OCF executive director and an oral cancer survivor, also stressed the importance of early detection and the important role that dentists play.  “Early detection is important because it reduces treatment-related morbidity and improves survival rates,” he said.

In 2010, the National Cancer Institute estimated that approximately 36,540 people were diagnosed with oral cancer and approximately 7,880 people died of oral cancer. The National Institute of Dental and Craniofacial Research (NIDCR) estimates that the five-year survival rate for people diagnosed early, when the disease has not spread beyond the original location, is approximately 83 percent compared to a 20 percent survival rate for those who were diagnosed when the cancer has spread to other organs.

In 2010, The Journal of the American Dental Association published “Evidence-based Clinical Recommendations Regarding Screening for Oral Squamous Cell Carcinomas” which was developed by an expert panel convened by the ADA Council on Scientific Affairs. The panel’s report concluded that clinicians should remain alert for signs of potentially cancerous lesions while performing routine visual and tactile examinations in all patients during dental appointments.

Risk factors for mouth and throat cancers include tobacco use, heavy consumption of alcohol, particularly when they are used together, as well as infection with the human papillomavirus, which is better known as HPV.

To locate free oral cancer screening programs in your area, please visit the OCF Web site here: To learn more about oral cancer, please visit the ADA’s Web site here:

Source: American Dental Association

Longitudinal study of human papillomavirus persistence and cervical intraepithelial neoplasia grade 2/3: critical role of duration of infection

Journal of the National Cancer Institute, April 5, 2011.
Authors: Ana Cecilia Rodríguez, Mark Schiffman, Rolando Herrero, Allan Hildesheim, Concepción Bratti, Mark E. Sherman, Diane Solomon, Diego Guillén, Mario Alfaro, Jorge Morales, Martha Hutchinson, Hormuzd Katki, Li Cheung, Sholom Wacholder, Robert D. Burk

The natural history of human papillomavirus (HPV) infections in older women is critical for preventive strategies, including vaccination and screening intervals, but is poorly understood. In a 7-year population-based cohort study in Guanacaste, Costa Rica, we examined whether women’s age and the duration of carcinogenic HPV infections influenced subsequent persistence of infection and risk of cervical intraepithelial neoplasia grade 2 (CIN 2) or worse disease.

At enrollment, of the 9466 participants eligible for pelvic examination, 9175 were screened for cervical neoplasia using multiple methods; those with CIN 2 or worse disease were censored and treated. Participants at low risk of CIN 2 or worse (n = 6029) were rescreened at 5–7 years (passively followed), whereas higher-risk participants (n =
2115) and subsets of low-risk women (n = 540) and initially sexually inactive women (n = 410) were rescreened annually or semiannually (actively followed) for up to 7 years. HPV testing was done using a polymerase chain reaction–based method. We determined, by four age groups (18–25, 26–33, 34–41, and ≥42 years), the proportion of prevalent infections (found at baseline) and newly detected infections (first found during follow-up) that persisted at successive 1-year time points and calculated absolute risks of CIN 2 and CIN grade 3 (CIN 3) or worse during follow-up. P values are two-sided.
Results Regardless of the woman’s age, newly detected infections were associated with very low absolute risks of persistence, CIN 2, or worse disease. For newly detected infections, the rate of progression to CIN 2+ (or CIN 3+), after 3 years of follow-up, was not higher for women aged 34 years and older than for younger women. Moreover, rates of newly detected infections declined sharply with age (in the actively followed group, at ages 18–25, 26–33, 34–41, and ≥42 years, rates were 35.9%, 30.6%, 18.1%, and 13.5%, respectively; P < .001). Among prevalent infections, persistent infections among older women (≥42 years) was higher than that among younger age groups or new infections at any age (P < .01 for comparison of eight groups). Most (66 of 85) CIN 2 or worse detected during follow-up was associated with prevalent infections. Only a small subset (25 of 1128) of prevalent infections persisted throughout follow-up without apparent CIN 2 or worse.

The rate of new infections declines with age, and new infections typically do not progress to CIN 2 or worse disease in older women; thus, overall potential benefit of prophylactic vaccination or frequent HPV screening to prevent or detect new carcinogenic HPV infections at older ages is low.

April, 2011|Oral Cancer News|

Late-stage cancer detection in the USA is costing lives

Source: The Lancet

In the USA, cancer is the most common cause of death in people aged between 49 and 80 years. In 2007, 562 875 cancer deaths were reported, which account for about 23% of all deaths. Cancers of the lung, colorectum, breast, and prostate are the most common and have the highest mortalities. In high-income countries remarkable progress has been made in cancer management and care, and although cancer incidence continues to rise, due to the influences of ageing, lifestyle, and population growth, mortality has fallen and survival rates are improving for several cancers, largely because of advances in screening, early detection, and treatment.

So in light of this progress, the US Centers for Disease Control and Prevention (CDC) report published last week makes for troubling reading, showing as it does that almost half of colorectal and cervical cancers and a third of breast cancers are being diagnosed at a late stage when treatment is less effective. The study is the first nationwide examination of stage-specific cancer incidence rates and screening prevalence for breast, cervical, and colorectal cancer by demographics including age and race or ethnic origin. The study found a lower uptake of screening and the presentation of symptoms late in low-income and ethnic minority communities, who also had longer delays in getting their diagnosis and treatment after an abnormal test. All these factors have been well documented to be associated with a late diagnosis for over a decade, so it is disappointing to see that cancer care is still failing the same patient groups. A further finding was the wide variation in late-stage diagnosis across different locations, which is a sad reflection of the fragmented health-care system in the USA. The CDC also reported that people without appropriate health insurance had less access to services despite the Patient Protection and Affordable

Care Act that is supposed to cover recommended screening tests by supporting people financially through co-payments.

Patient delay can be a major factor behind late diagnosis; many patients are unaware of (or ignore) the symptoms of cancer; and health literacy, cultural attitudes towards seeking medical care, fear and embarrassment of a cancer diagnosis, and difficulties navigating the health-care system all play a part. But physicians can add to delays by failing to recognise sentinel signs and by failing to triage the right patients forward for further investigation. Symptoms of early cancer can be non-specific and mistaken for other conditions, a factor behind the late presentation of ovarian or pancreatic cancers, for example. Biomarkers could have a role in helping to identify and stratify high-risk populations. Education of both the patient and general physician is essential to move to an early diagnosis of cancer. For example, if patients have a family history of certain cancers, such as colorectal or breast cancer, then these individuals can present earlier than might be expected. Both patient and physician should be aware of these indicators and appropriate screening programmes made available to all who need them.

A shortcoming of the CDC report is the lack of discussion about the nature of diagnostic tests and the challenges they present. For colorectal cancer, the fecal occult blood test is not discriminative, and the follow-up tests of sigmoidoscopy or colonoscopy are invasive and not without risk. Although, encouragingly, the recent trial of once-only flexible sigmoidoscopy screening has been shown to be safe and practical. However, overdiagnosis and overtreatment can limit the effectiveness of screening in the general population; thus, identification of high-risk groups is crucial. There is a need for better initiatives to support the development of specific tests for particular cancers and to direct treatment to specific patient groups.

Several initiatives to promote early diagnosis in symptomatic patients are noted in the report and should be credited. The CDC have recently established the Colorectal Cancer Control Program, which provides funding to 25 states and four tribal organisations to promote screening and follow-up care to low-income individuals who are uninsured for screening. The CDC’s National Comprehensive Cancer Control Program provides funding and technical assistance to all states and minority community organisations to develop and implement coordinated cancer control plans to provide a continuum of services including prevention, early detection, treatment, survival, and palliation.

Efforts to identify people most at risk of cancer and those who are difficult to reach must continue to be a priority if the alarming statistics in the CDC report are to improve. More research aimed at improving diagnostic tests and biomarker development would complement and improve early clinical diagnoses, and should go hand-in-hand with the removal of patient and physician barriers to effective cancer care.

December, 2010|Oral Cancer News|

Latest generation VELscope device approved for sale by Health Canada

Author: staff

LED Dental Inc. announced today that its VELscope Vx Enhanced Oral Assessment system was granted a medical device license and approved for sale by Health Canada. The VELscope Vx system’s unique cordless design and affordable pricing make it easier than ever for dental practices to detect oral cancer and other forms of oral disease.

The first-generation VELscope device was introduced in 2006, with the second-generation version launching two years later. In total, LED Dental has sold almost 6,000 units of the two devices, which have been used to conduct almost 10 million enhanced oral soft tissue exams worldwide. Oral soft tissue exams not only help detect all types of oral disease but are also a key element of an oral cancer screening protocol. Today, VELscope fluorescence visualization technology is used to conduct more enhanced oral exams than any other detection technology in the world.

“We are extremely excited about the potential of the VELscope Vx system to significantly increase the number of dental practices conducting oral cancer screenings,” said Peter Whitehead, founder and CEO of LED Dental. “The device’s portability makes it easy to transport between operatories within the dental practice, and its attractive pricing makes it possible for practices to charge very low exam fees to their patients.”

Oral cancer kills one North American every hour of every day. According to the SEER database, oral cancer has a higher mortality rate than several better-publicized cancers, such as cervical cancer and testicular cancer. Some oral cancers are now known to be linked to exposure to the sexually-transmitted human papilloma virus (HPV), which means that anyone who is sexually active is potentially at risk for the disease. Because of this, many health experts advise everyone 18-years-old and older to get an oral cancer exam on at least an annual basis.

Regular exams can help address the fact that oral cancer is typically discovered in late stages, when the 5-year survival rate is around 30%. When discovered in early stages, however, the survival rate leaps to 80-to-90%, according to SEER data. Early detection can help reduce not only the mortality rate, but the degree of invasiveness and disfigurement resulting from treatment.

The VELscope Vx shines a safe, blue light into the oral cavity and excites natural tissue fluorescence. When viewed by the clinician through the Vx’s patented filters, abnormal tissue typically appears as an irregular, dark area that stands out against the otherwise normal, green fluorescence pattern of surrounding healthy tissue.

VELscope Vx exams can help dental practices detect not only oral cancer, but other more common types of oral disease, such as infections. Exams take only a few minutes, and are completely free of any pain or inconvenience for patients.

October, 2010|Oral Cancer News|

‘Synthetic lethality’ strategy improves molecularly targeted cancer therapy

Author: Fox Chase Cancer Center

Molecularly targeted therapies can reduce tumors rapidly. However, not all tumors respond to the drugs, and even those that do often develop resistance over time. Looking for a way to combat the problem of resistance, researchers at Fox Chase Cancer Center hypothesized that hitting already weakened cancer cells with a second targeted agent could kill them—but only if it was the right second agent.

One well-validated molecular target for anti-cancer drugs is the epidermal growth factor receptor, or EGFR. Using a novel screening approach, investigators in the Fox Chase Developmental Therapeutics Program identified over 60 additional proteins that are necessary for cells to survive in the presence of an EGFR inhibitor. When they simultaneously blocked the EGFR inhibitors and any one of these other proteins, more of the cancer cells died. The researchers say this screening strategy to identify targets for effective combinations of cancer drugs will open the door for future therapies. Already, two clinical trials are under way to test innovative drug combinations suggested by the new tactic.

“We found that knocking out one or the other target doesn’t have a major effect, but knocking out both increases tumor cell death,” says Igor Astsaturov, M.D., Ph.D., an assistant professor and medical oncologist at Fox Chase. Astsaturov led the study, which will be published in the September 21, 2010 issue of Science Signaling.

To identify additional targets that would boost the effectiveness of EGFR inhibitors against cancer, Astsaturov and colleagues screened only proteins that interact directly or indirectly with EGFR. The team mined the literature and built a candidate set of 638 EGFR-interacting proteins. They then used an experimental technique called small inhibitory RNA (siRNA) systematically to block activity of each of the genes in cancer cells that had been treated with an EGFR inhibitor. In doing so, the investigators demonstrated on three clinically relevant examples for which drugs are already available—PRKC, STAT3, and Aurora kinase A—that these proteins were necessary for cell survival in the presence of an EGFR inhibitor.

This two-hit strategy—where neither hit is adequate to kill the cells, but together they are—is called synthetic lethality. Geneticists have used synthetic lethal screens in experiments with model organisms, such as fruit flies and yeast, for decades, but cancer researchers have only recently adopted the approach.

“We knew from model organisms that there was a dense network of genes. Using bioinformatics tools to intelligently mine this network provided us with a rich source of hits,” says Erica A Golemis, Ph.D., professor and co-leader of the Developmental Therapeutics Program at Fox Chase, and senior author on the new study. Golemis is also co-leader of the Keystone Initiative in Head and Neck Cancer at Fox Chase, and notes that EGFR inhibitors are already broadly used in the clinic for cancers affecting the head and neck.

“The most exciting hit is the Aurora kinase,” Golemis says. Several Aurora kinase inhibitors are already being tested in the clinic and thus are available for testing in combination with EGFR inhibitors.

Based on the new data, Hossein Borghaei, D.O., director of the Lung Cancer Risk Assessment Program at Fox Chase is launching a trial testing the EGFR inhibitor erlotinib with an Aurora kinase inhibitor in patients with non-small cell lung cancer. Astsaturov has started testing a drug called vandetanib—which simultaneously inhibits EGFR and RET (another protein in the EGFR-interacting network)—in patients with esophageal cancer.

In addition to providing a rich source of synthetic lethal hits, limiting the siRNA screen to a previously-defined network of interacting proteins had an important impact on the size of the project, according to Golemis. “A full genome siRNA screen is prohibitively expensive for many labs. This approach makes siRNA screens more accessible to smaller labs and academic institutions.”

September, 2010|Oral Cancer News|

HPV is changing the face of head and neck cancers

Author:  Christen Cona

In February, at the Multidisciplinary Head and Neck Cancer Symposium in Chandler, Ariz., Maura Gillison, MD, PhD, professor and Jeg Coughlin Chair of Cancer Research at The Ohio State University in Columbus, presented data that showed that the proportion of all head and neck squamous cell cancers that were of the oropharynx — which are most commonly HPV-positive cancers — increased from 18% in 1973 to 32% in 2005.

Maura Gillison, MD, PhD, Jeg Coughlin Chair of Cancer Research at The Ohio State University, said screening for HPV in the head and neck is years behind cervical screening for HPV. - Photo by Roman Sapecki

In addition, studies from the United States, Europe, Denmark and Australia indicate that HPV-positive patients have a more than twofold increased cancer survival than HPV-negative patients, according to Gillison.

With the rising incidence of HPV-related oropharynx cancers, it will soon be the predominant type of cancer in the oral or head and neck region, according to Andy Trotti, MD, director of radiation oncology clinical research, H. Lee Moffitt Cancer Center & Research Institute, in Tampa, Fla.

“We should be focusing on HPV-related oropharyngeal cancer because it will dominate the field of head and neck cancers for many years,” he said during an interview with HemOnc Today . “It is certainly an important population for which to continue to conduct research.”

Because HPV-associated oropharyngeal cancer is emerging as a distinct biological entity, the recent rise in incidence will significantly affect treatment, and prevention and screening techniques, essentially reshaping current clinical practice.

Social change driving incidence
In the analysis performed by Gillison and colleagues, trends demonstrated that change in the rates of head and neck cancers was largely due to birth cohort effects, meaning that one of the greatest determinants of risk was the year in which patients were born.

The increased incidence of HPV-related oropharyngeal squamous cell carcinoma started to occur in birth cohorts born after 1935, indicating that people who were aged in their teens and twenties in the 1960s were demonstrating increased incidence, Gillison said.

“Two important and probably related events happened in the 1960s. In 1964, the surgeon general published a report citing smoking as a risk factor for lung cancer, and public health policy began promoting smoking cessation along with encouragement not to start smoking,” she told HemOnc Today.

If you were 40 years old between 2000 and 2005, your risk for having HPV-related cancer is more than someone who was between the age of 40 and 45 years in 1970, according to Gillison. Social changes that occurred among people born after 1935, for example, a reduction in the number of smokers, is consistent with the increasing proportion of oropharyngeal cancers that were HPV-related.

“The rates for HPV-related cancers began to increase and the rates for HPV-unrelated cancers started to decline, consistent with the known decline in tobacco use in the U.S. population,” she said.

Now, most cases of head and neck squamous cell carcinoma in non-smokers are HPV-related; however, oral HPV infection is common and is a cause of oropharyngeal cancer in both smokers and non-smokers, research shows.

In addition to a decrease in tobacco use reducing HPV-unrelated oral cavity cancers, the number of sexual partners may have increased during this time and have helped to increase HPV-related oropharyngeal cancers, according to Gillison.

Determining the cause of the elevated incidence is only a small piece of the puzzle. Screening, establishing who is at risk, and weighing vaccination and treatment options are all relevant issues that must be addressed.

Screening is problematic
A critical area for examination and research is the issue of screening for oral cancers. In contrast to cervical cancer, there is no accepted screening that has been shown to reduce incidence or death from oropharyngeal cancer, according to Gillison.

Not many studies have examined the issue of screening for HPV-unrelated oral cancers, and the few that have, tend to include design flaws.

Gillison said there is a hope that dentists would examine the oral cavity and palpate the lymph nodes in the neck as a front-line screen for oral cancer; however, in her experience, and from her perspective as a scientist, this has never been shown to provide benefit for oral cancer as a whole.

Another caveat with regard to HPV detection is that head and neck HPV screening is about 20 years behind the cervical field.

“Clinicians screening for HPV in the field of gynecology were incredibly fortunate because Pap smear screening was already an accepted cervical cancer screening method before HPV was even identified,” she said. “There was already a treatment algorithm: If there were cytologic abnormalities, patients were referred to the gynecologist, who in turn did a colposcopy and biopsy.”

A similar infrastructure does not exist for oropharyngeal cancer. People with HPV16 oral infection are at a 15-fold higher risk for oropharynx cancer and a 50-fold increased risk for HPV-positive head and neck cancer, yet there is no algorithm for treatment and management of these at-risk individuals, Gillison said.

In 2007, WHO said there was sufficient evidence to conclude that HPV16 was the cause of oropharynx cancer, but with no clinical algorithm already established, progress in this area is much further behind.

Another problematic aspect of HPV-related oropharyngeal cancer screening is that the site where the cancer arises is not accessible to a brush sampling, according to Gillison.

“To try to find this incredibly small lesion in the submucosal area that you cannot see and cannot get access to with a brush, highlights that we need to develop new techniques, new technologies and new approaches,” she said.

The near future consists of establishing the actual rates of infection in the oral cavity and oropharynx, and then screening for early diagnosis, according to Erich Madison Sturgis, MD, MPH, associate professor in the department of head and neck surgery and the department of epidemiology at The University of Texas M.D. Anderson Cancer Center.

“I am not extremely hopeful because the oropharyngeal anatomy makes screening complicated, and these cancers likely begin in small areas within the tonsils and the base of the tongue,” Sturgis told HemOnc Today. “I am hopeful, however, that preventive vaccines will eventually, at a population level, start to prevent these cancers by helping people avoid initial infection by immunity through vaccination earlier in life.”

Much of the currently known information surrounding the issue of HPV-related oral cancers is new, so researchers continue to conduct research in various relevant areas. One key question to answer is who may be at higher risk for HPV-related oropharynx cancers.

Who is at risk?
As mentioned earlier, the number of oral sex partners seems to play a role in the risk for contracting the HPV virus.

In one study published in The New England Journal of Medicine in 2007, findings demonstrated that a high lifetime number of oral sex partners (at least six partners) was associated with an increased risk for oropharyngeal cancer (OR=3.4; 95% CI, 1.3-8.8).

In addition to a higher number of oral sex partners, other still unknown factors may be contributing to risk. This is an area that needs further research, according to Barbara Burtness, MD, chief of head and neck oncology, and professor of medical oncology at Fox Chase Cancer Center in Philadelphia.

The effect of smoking status is another area that needs further research. According to Burtness, smokers with HPV-associated oropharynx cancer have less favorable outcomes.

When discussing the prognosis of HPV-associated cancers, Sturgis said low risk is defined as low or no tobacco exposure and positive HPV status, and intermediate risk is defined as significant tobacco exposure but an HPV-positive tumor, and the highest risk group appears to be the HPV-negative group.

Although HPV-negative cancers are overwhelmingly tobacco-related cancers and tend to have multiple mutations, it appears that HPV-positive cancers, particularly those in patients with low tobacco and alcohol exposure, tend to lack mutations and to have a better prognosis, and this may ultimately help to guide treatment practices, according to Sturgis. Yet, there is still much to learn about HPV-related oropharyngeal cancers on various fronts.

Vaccination a hopeful ally
In HPV-related head and neck cancer, particularly oropharynx cancers, more than 90% of patients who have an HPV-type DNA identified, have type 16, according to Sturgis.

The two current HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), which are approved for cervical cancers, include HPV types 16 and 18; therefore, in theory, they should be protective against the development of infections in the oropharynx and protective at preventing these HPV-associated cancers from occurring.

The presumption is that if there was a population-wide vaccination against HPV, there would be less person-to-person transmission, and this would lead to fewer oropharynx cancers, according to Burtness, who said this theory still needs further research.

There is excitement at the possibility that therapeutic vaccines could be developed, and various groups are investigating this, Burtness added.

“There is reason to think that the vaccines may be helpful; however, when HPV infects the tonsillar tissues, it exerts control in the host cells by making two proteins: E6 and E7; so another potentially exciting therapeutic avenue would be to target those specific viral proteins,” she told HemOnc Today.

Anxiety about protection from the HPV virus is palpable, according to Sturgis. He described the worry that many patients experience about contracting and transmitting HPV infection.

“Many patients are concerned they will put their spouses and/or children at risk in ways such as kissing them; and we need to tone down those worries until we have better data,” he said.

Screening and vaccination are fundamental aspects of current ongoing research, but of equal importance is determining what clinicians should do to treat a population of patients with HPV-related oropharyngeal cancers.

HPV status may influence treatment
With rates of HPV-related cancers escalating, determining the appropriate treatment for these patients is crucial.

During the past 10 years, findings from retrospective studies have shown that patients with HPV-related cancers have a much better prognosis than patients who test negative for HPV. Findings from several retrospective analyses from clinical trials conducted during the past 2 years have come to the same conclusion, according to Gillison: HPV-positive patients have half the risk for death compared with patients negative for HPV.

Therefore, there may be several alternative treatment options, including the possibility of reducing the dose of radiation given to patients after chemotherapy, thereby reducing toxicity.

Comparing HPV-negative and HPV-positive patients may not be enough to determine proper treatment, researchers said. Data between different cohorts of HPV-positive patients also needs to be examined. Smoking, for example, may play a role in patient outcome.

In a prospective Radiation Therapy Oncology Group clinical trial (RTOG 0129), presented by Gillison at the 2009 ASCO Annual Meeting and recently published in The New England Journal of Medicine (see page 53), researchers conducted a subanalysis of the effect of smoking on outcome in uniformly staged and treated HPV-positive and HPV-negative patients while accounting for a number of potential confounders. HPV-positive patients who were never smokers had a 3-year OS of 93% compared with heavy smoking HPV-negative patients who had an OS of 46%.

The study found that smoking was independently associated with OS and PFS. Patients had a 1% increased risk for death and cancer relapse for each additional pack-year of smoking. This risk was evident in both HPV-positive and HPV-negative patients. Gillison said smoking data must be paid attention to, and she encouraged cooperative group research on the topic.

Most of the findings demonstrate improved outcomes for patients with HPV-positive oropharyngeal cancers vs. patients with HPV-negative oropharyngeal cancers, according to the experts interviewed by HemOnc Today.

Dose de-intensification for less toxicity
To date, there is no evidence that HPV-related cancers should be managed differently than HPV-unrelated cancers, but it is a hot topic among clinicians in the field, according to Burtness.

The superior outcomes for HPV-associated oropharynx cancer have suggested the possibility of treatment de-intensification. The use of effective induction chemotherapy may permit definitive treatment with a lower total radiation dose. In theory, this would reduce the severity of late toxic effects of radiation, such as swallowing dysfunction. Such a trial is being conducted by the Eastern Cooperative Oncology Group. Burtness said this is currently pure research question.

“There is still much research that needs to be done before clinicians can safely reduce the dose of radiation administered to HPV-positive patients,” Burtness said.

Currently, she and colleagues in the ECOG are conducting a study of patients with HPV-associated stage III or IV oropharynx cancers to examine the possibility of tailoring therapy to these patients. Patients are assigned to one of two groups: low-dose intensity-modulated radiotherapy 5 days per week for 5 weeks (27 fractions) plus IV cetuximab (Erbitux, ImClone) once weekly for 6 weeks, or standard-dose intensity-modulated radiotherapy 5 days per week for 6 weeks (33 fractions) plus IV cetuximab once weekly for 7 weeks.

If patients have a very good clinical response to chemotherapy, which is likely to happen with HPV-associated cancers, they are eligible to receive a reduced dose of radiation, and hopefully, they would experience less adverse effects, Burtness said.

“Patients who are treated with the full course of radiation for head and neck cancer are now getting 70 Gy, and they are often left with dry mouth, and speech and swallowing difficulty,” she said. “We are hopeful that if these particular cancers are treatment responsive to chemotherapy, we may be able to spare the patient the last 14 Gy of radiation.”

Immunotherapy a viable treatment
Another possible treatment technique that may benefit patients with HPV-related cancers is immunotherapy. One form of immunotherapy uses lymphocytes collected from the patient, and training the cells in the laboratory to recognize in this case a virus that is associated with a tumor and consequently attack it. This approach potentially may be used to treat HPV-related oropharynx cancers, according to Carlos A. Ramos, MD, assistant professor at the Center for Cell and Gene Therapy at Baylor College of Medicine, Houston.

“With some infections that lead to cancer, even though the virus is present in the tumor cells, the proteins shown to the immune system are limited; therefore, they do not drive a very strong immune response,” Ramos told HemOnc Today. “Training the immune system cells, T lymphocytes, may make them respond better to antigens.”

Data from ongoing trials that are taking T lymphocytes from patients and educating them to recognize antigens in patients with the Epstein-Barr virus associated tumors have shown some activity against them, according to Ramos. This adoptive transfer appears to be safe and may have the same effect on the HPV virus associated tumors. Immunotherapy does not cause the usual toxicities associated with chemotherapy, he said.

“There are currently no trials showing whether we can prevent more recurrences with this approach, but the results of trials examining viruses such as Epstein-Barr are good so far, in both patients who have no evidence of disease and in those who still have disease,” he said.

Even patients with active disease who have not responded to other therapies have responded to this therapy, Ramos said. He and colleagues are working toward compiling preclinical data to study the possibility of using immunotherapy to treat patients with HPV-related cancers.

Journey is just beginning
Much of what is known about risk, screening, prevention and treatment of HPV-related oropharynx cancers is in the early stages of discovery and much is still theoretical, according to Sturgis.

“As far as we can tell, these infections are transmitted sexually; the hope is that as we have better vaccines for prevention of cervical dysplasia, the downstream effect will help prevent other HPV-related cancers, such as anal cancers and penile cancers and oropharyngeal cancers,” he said.

Several recent studies examining new therapies that may reduce the intensity of traditional treatments while maintaining survival rates would have a major effect on the field, according to Sturgis.

Gillison said the rise in the number of cases of HPV-related cancers is changing the patient population considered to be at risk, and more research is vital.

“The most important thing for clinicians to do is be aware that trials are being developed and strongly encourage their patients to participate,” she said.

ADA unveils oral cancer evidence-based recommendations

Author: Jennifer Garvin

A panel convened by the ADA Council on Scientific Affairs explored the potential benefits and risks of screening for oral squamous cell carcinomas and the use of screening aids to detect malignant or potentially malignant oral lesions. The panel’s findings are published as the cover story in the May edition of The Journal of the American Dental Association.

“Evidence-Based Clinical Recommendations Regarding Screening for Oral Squamous Cell Carcinomas” were developed by a CSA expert panel convened in April 2009, and join similar recommendations on topical fluoride and sealants as the Association’s only evidence-based recommendations.

Though evidence-based dentistry (EBD) recommendations do not represent a standard of care, the CSA hopes practitioners will use the recommendations as a resource in their clinical decision-making process alongside a clinician’s judgment and experience in the context of a patient’s individual needs.

The panel worked with ADA Center for Evidence-Based Dentistry staff and assessed five systematic reviews and four clinical studies as a basis for developing the recommendations. They addressed whether or not screenings help reduce morbidity and mortality, and whether or not oral cancer detection devices aid in detecting potentially malignant or malignant lesions.

The panel concluded that while oral cancer screenings may detect potentially malignant and/or malignant lesions, clinicians are urged to remain alert for signs the lesions may become cancerous or early stage cancers while performing routine visual and tactile examinations in all patients, particularly those who use tobacco or consume alcohol heavily.

“What’s most important is that this (review) points to the need for more research on the natural history of squamous cell carcinomas in the mouth and the epidemiology of oral cancer,” said Dr. Michael Rethman, CSA chair. “We still don’t understand the answers to a lot of fundamental questions like the progression of the disease and whether intervention helps. It’s plausible that early diagnosis helps, but we don’t even know that,” he added.

“There’s an incredible need for more research on this topic,” he added.

For more information about the ADA’s clinical recommendations, visit

To see the May issue of JADA, go to

1. In developing the evidence-based clinical recommendations for oral squamous cell carcinomas, the ADA Council on Scientific Affairs considered the following four questions:

  • Does screening through visual and tactile examination performed by a dentist reduce morbidity and mortality resulting from potentially malignant or malignant lesions?
  • Does the use of the following adjuncts (autofluorescence, tissue reflectance and transepithelial cytology) by a dentist, in conjunction with visual and tactile examination, reduce morbidity and mortality from oral cancer to a greater extent than that experienced with visual and tactile examination alone?
  • In comparison with visual and tactile examination alone, do the currently available oral cancer detection devices enhance the diagnostic properties (such as sensitivity, specificity, positive and negative predictive values) in detection of potentially malignant or malignant lesions?
  • Are there specific population subgroups—defined by age, sex, ethnicity, risk factors or other characteristics—in which oral cancer screening has relatively high positive and negative predictive values, resulting in detection of potentially malignant or malignant oral lesions?

Isn’t it about time? Overcoming the real barriers to complete oral cancer screening

Author: Jonathan A. Bregman, DDS, FAGD

In the previous articles of this series, I discussed four barriers I see as stopping those in the dental profession from doing a complete oral cancer screening examination.

In Part 1, the barrier I discussed is the overall lack of confidence in doing a complete extra-/intraoral cancer screening exam. The rationale: “not doing the exam at all puts me at less risk than doing it and missing something.”

In Part 2, the barrier I discussed is being unclear about who to examine: the changing target population, especially the influence of the human papillomavirus (HPV 16/18).

In Part 3, the uncertainties of how the complete cancer screening examination should be done, plus communicating the reasons for doing it for patients.

In Part 4: Uncertainty about how to properly record the cancer screening examination

Barrier 5: Uncertainty about how to best and most effectively deliver the message of a positive finding

The more we look, the more we find.

The more we look, the closer we look, the more abnormalities we will detect with our cancer screening exam. This makes sense, of course. The same goes for the complete periodontal examination, the complete occlusal analysis, the complete updated radiographic evaluation, etc.

In each area — tissue abnormalities, periodontal abnormalities, occlusal abnormalities — we must address the needs of the patient in a way that sets the stage for understanding of the problem(s) and presenting possible options/solutions to correct the problems.

Build on what you already know

In every program I do on this important aspect of doctor/team and patient communication, I ask the same question, “What difficult message have you delivered in the past four to five days you have been in your office treating patients?”

The answers are varied.

* “You need a root canal. And afterwards, you need a build-up and a crown!!”
* “You will lose this tooth (or this front tooth).”
* “You will lose all of your teeth.”
* “You have a disease in your mouth called periodontal disease that, if left untreated, can cause heart damage and lead to a variety of maladies including pancreatic cancer.”
* “The crown (bridge) is failing and needs to be replaced.”

So, how do you consistently set the stage to effectively deliver these messages?

Creating the right environment is the first step

Think about what you do when having a difficult discussion with a patient.
What is your body position in relation to theirs?

* Behind?
* To the side?
* Across the room?

Most of you would say, “On eye level, right in front of the patient, and close enough to have this conversation, but not too close to invade personal space.”

And what would the overall environment be like?

* Noisy?
* People coming and going
* In a public space

Once again, the unanimous reaction is, “A quiet, private space that lends itself to this important communication.”

Establishing the demeanor of the ‘giver of the difficult message’ is the second step

How do you act when you meet with your patient to discuss a difficult problem?

* Preoccupied with what you have to get back to doing?
* Distracted?
* Judgmental of the patient’s reaction?

You are probably thinking, “Of course not! I am totally focused on the patient and react in a totally nonjudgmental manner.” Yes, that is indeed critically correct.

I have set the stage with the right environment and approach with the most effective demeanor. NOW WHAT?

The third step is effectively working through the four key aspects of delivering the message of a positive finding from an oral cancer screening examination.

One: Clearly and simply state the message in as few words as possible.

Example: “Ms. Jones, I have found an abnormality on the side of your tongue. It is a mixed red and white patch. I am referring you to an excellent doctor who will help to diagnose this abnormality.” (Or, “We will do a biopsy to determine exactly what this abnormality is.”)

Two: Just be quiet, listen, watch, and gauge the patient’s reaction.

One patient might very calmly say, “Well, I guess we need to find out what it is. What is the next step for me?” Another patient might become hysterical or totally melt down.

By saying nothing at this time, you will be able to determine the best way to help your patient proceed instead of assuming (and we all know what the word “assume” breaks down to be!) their needs and going into a long discussion or explanation that may or may not meet their needs.

Three: Use active listening when discussing the patient’s concerns and answering his or her questions.

Active listening is accomplished by using a feedback approach to a conversation to clarify questions being asked and concerns felt.

For example: “So I am hearing that you are very concerned about this area on your tongue since you sing in the church choir and are afraid that it would stop you from doing what you love to do. Is that right?”

Another example: “So that I am clear, are you asking me how long you can wait to make the appointment with the specialist or to have a biopsy done our office?”

Peter Barry, a premier speaker, trainer, and dental consultant, stated the following during one of his recent programs. “Our patients need for us to know that we not only hear them (one of the six senses) but actually are listening to them.” I could not agree more.

Active listening accomplishes these two key goals:

1. Our patients know that we are really listening to them.
2. There is no confusion as to what the patient is asking or feeling.

Four: Ensure that there are no further questions and clarify the next steps that the patient must take.

One of the first lessons in communications that I teach is how to find out if patients understood what was said to them and if they had any further questions.

If you say, ”So, do you understand?” Unspoken, the word “dummy,” will almost always get a “yes” because who wants to be dumb. BUT, if the phrasing of the question is changed to “Is there anything I have not made clear to you today?” and “Do you have any other questions or concerns I have not answered?” opens the door to any further clarification the patient may need.

So be clear that the patient’s questions and concerns have been answered, hand out your business card in case other questions come up after the patient leaves, and hand the patient off to the person who will help him or her take the necessary next steps of scheduling an appointment with the specialist.

One warning: don’t guess. Stick to your ‘mantra.’

Patients will always ask, “So what do you think this is” or “Should I really be concerned about this?” or “Do you think that this is cancer?’



“We only know that this is an abnormality. We need to diagnose exactly what it is.” Or, “It is not good dentistry and not fair to you for me to guess at a diagnosis, which is why we are going to find out what this abnormality is or is not.”

Don’t let the need to deliver the difficult message of a positive finding from your cancer screening exam be a barrier for you and your practice.

1. You have done this before: use what you have learned about the effective delivery of other difficult messages and apply those same principles to the detection of an oral abnormality.

2. Create an environment that is “patient friendly” for delivery and receipt of this important message.

3. Remember the four key aspects for the delivery of the message:

* One: State the problem simply and clearly.
* Two: Stop, be quiet, listen, and observe.
* Three: Use active listening techniques to make certain that the patient knows that you are truly listening to him or her and to prevent misunderstandings.
* Four: Wrap up the question segment using the correct communication skills and turn the patient over for the next step, which is either a referral to a specialist or reappointing in your office for a biopsy.

4. Don’t guess at a diagnosis. Let the definitive biopsy establish the diagnosis not your screening exam.


What’s coming up next article in this series?

Resistance factor six: Creating a seamless referral system and follow-up protocols.

1. Jonathan A. Bregman, DDS, FAGD, is a clinician, speaker, author, and trainer who led successful dental practices for more than 30 years. While dedicated to improving the dentist, team, and patient experience, he has a passion for educating dental professionals about early oral cancer detection and laser-assisted dentistry. You may contact Dr. Bregman by e-mail at or visit Also be sure to check out his blog at

March, 2010|Oral Cancer News|