Trial Confirms Efficacy of HPV Vaccine, Shows Cross-Protection

Source: National Cancer Institute

End-of-trial results from a trial testing Cervarix, a vaccine against human papillomavirus (HPV) types 16 and 18, showed that the vaccine continued to provide substantial protection against cervical precancers 4 years after vaccination. Cervarix provided almost complete protection in young women who had no evidence of exposure to HPV at the time of vaccination. The vaccine provided less protection for the total vaccinated cohort and was less effective with increasing age at vaccination. These findings reflect the vaccine’s lack of effectiveness against infections acquired before vaccination.

The vaccine also partially protected women against four types of HPV that are not targeted by the vaccine. (Although HPV-16 and -18 cause about 70 percent of cervical cancers worldwide, as many as 15 HPV types can cause cancer.) These results from the PATRICIA trial (Papilloma Trial against Cancer in Young Adults) were published online November 9 in Lancet Oncology in two separate papers, available here and here.

The PATRICIA trial enrolled 18,644 young women between the ages of 15 and 25 from 14 countries. The participants were randomly assigned to receive either three doses of Cervarix or three doses of a hepatitis A vaccine as a control. Results from the interim analysis, published in July 2009, showed that the vaccine greatly reduced the risk of grade 2 cervical intraepithelial neoplasias and higher (CIN2+).

The new analysis shows that, 4 years after vaccination, Cervarix provided complete protection against grade 3 cervical intraepithelial neoplasias or higher (CIN3+) associated with HPV-16 and -18 among women who had no evidence of exposure to HPV. The vaccine provided strong protection against CIN3+ caused by other HPV types in this same group of women. Among the total cohort of women who received at least one dose of Cervarix, some of whom may have had prior exposure to HPV, the vaccine provided some protection. (See the table below.)

Cervarix Vaccine Efficacy among Women Who Received at Least One Dose of Cervarix

Women with no evidence of HPV exposure at baselineWomen who may have had prior exposure to HPV

Against CIN3+ associated with HPV-16 and -18


100 percent


45.7 percent


Against all CIN3+, regardless of HPV type


93.2 percent


45.6 percent


Against all adenocarcinoma in situ


100 percent


76.9 percent

The vaccine provided cross-protection against HPV-33, HPV-31, HPV-45, and HPV-51, all cancer-causing types of the virus. The researchers speculate that the observed cross-protection may be due either to the vaccine adjuvant (a substance that stimulates the immune system) or to similarities among proteins found on the surfaces of different HPV types.

In an accompanying editorial, Drs. Mark Schiffman and Sholom Wacholder of NCI’s Division of Cancer Epidemiology and Genetics, who were involved with the NCI Costa Rica HPV vaccine trial, noted the importance of the PATRICIA trial results. They also stated that “the practical aspects of vaccine uptake are now the most important issue in HPV vaccine research from a public health perspective.” To increase vaccine uptake in the developing world, where 90 percent of cervical cancer cases occur, next-generation HPV vaccines will need to be less expensive, provide protection in a single dose, and/or be stable without refrigeration, they explained.

Further reading: “Second Cervical Cancer Vaccine Protects against Additional HPV Types” and “Use and Acceptance of HPV Vaccine Still a Work in Progress

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

November, 2011|Oral Cancer News|

Protein inhibitor may supply contemporary HPV treatment

Source: Dr.Bicuspid.com

Researchers from Tufts University School of Medicine have developed a protein-based inhibitor that could provide a topical treatment for HPV as an alternative to surgical and harsh chemical treatments (FASEB Journal, April 11, 2011).

HPV affects about 20 million people in the U.S., 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.

“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, PhD, an associate professor of biochemistry at Tufts University School of Medicine.

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.

“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,” Baleja said. “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 added.


April, 2011|Oral Cancer News|

Oral cancer: How discovery devices assist screenings

Source: www.dentistryiq.com
Author: Nick Efthimiadis, Vice President, Sales & Marketing, LED Dental Inc.

As the intense media attention surrounding Michael Douglas’s illness clearly demonstrated, oral cancer is increasingly in the news these days. With the unfortunate growth in the number of relatively young people contracting the disease due to exposure to the sexually-transmitted human papilla virus — specifically, the HPV-16 strain — oral cancer will only become a bigger concern for both patients and dental practices over time. In fact, the Oral Cancer Foundation recently announced that HPV-16 has now replaced tobacco as the leading cause of this disease.

Sadly, one North American dies every hour of every day from oral cancer, and many of those who survive the disease are forced to deal with lengthy, painful treatment and permanent disfigurement. The main problem is that oral cancer is typically discovered in late stages, when the five-year survival rate is only around 30%.

The good news: when discovered early, the survival rate leaps to 80%-to-90%.

The key to early discovery is the dental practice. Ideally, each and every practice should be conducting a two-step oral cancer screening on all adult patients as part of their annual or semi-annual hygiene checkup. The first step consists of a conventional “white light” exam comprising visual inspection and palpation. The second step consists of examination with an adjunctive screening device. Fortunately, the two steps should take no more than five minutes combined.

Palpation as part of the "white light" exam

For the past several years, the adjunctive device that has been used for more screenings than any other is the VELscope system. It is the first technology to be approved by the FDA and Health Canada to help clinicians detect cancerous and pre-cancerous lesions that might not be apparent to the naked eye. What made this possible is that the VELscope was also the first product to bring tissue fluorescence visualization technology to dentistry, and it is still the industry’s gold standard. In fact, since its 2006 launch, VELscope devices have been used to conduct over 10 million exams.

In many practices, both the conventional and VELscope screenings are conducted by the hygienist.

Hygienist uses adjunctive device as part of oral cancer screening

The VELscope handpiece shines a safe blue light into the oral cavity. When viewed through the VELscope’s patented filters, healthy tissue fluoresces green. Suspicious tissue, such as oral abnormalities that may be or may lead to dysplasia and oral cancer, has a different fluorescence signature and generally appears as a dark, irregularly shaped patch. If a suspicious lesion is detected, the hygienist will normally have the dentist view it using the VELscope as well. In some cases, questioning of the patient may reveal a logical explanation, such as a burn from hot coffee. If the lesion cannot be explained, the dentist will normally ask the patient to return for a follow-up screening in two or three weeks. If the condition has not improved, the dentist will usually perform a surgical biopsy or refer the patient to a specialist for a biopsy.

Doctor checks suspicious lesion

It is important to note that the VELscope is a discovery device, not a diagnostic device. Only a surgical biopsy can provide an accurate diagnosis of a lesion. In some cases the diagnosis will be cancer, pre-cancer or dysplasia, but more often some other type of oral disease will be diagnosed. Examples include lichen planus and bacterial, viral and fungal infections. While these conditions are clearly much less serious than cancer, they are conditions that need to be discovered and treated.

The latest and most advanced generation of VELscope technology was recently introduced. The VELscope Vx Enhanced Oral Assessment system does everything prior generations did, but features two dramatic improvements. First, it is cordless and lightweight, making it exceptionally portable. Second, the price has been cut roughly in half; in fact, its $2,499.99 regular price makes it possible for many practices to have a VELscope Vx in every operatory.

There are many other advantages of the VELscope Vx system:

* It is easy to incorporate into the practice.
* It is completely noninvasive for the patient, with no rinses, dyes or discomfort.
* Any suspicious lesions can be easily photo-documented and shared with specialists who might be conducting surgical biopsies.
* It gives the patient wonderful peace of mind, since the vast majority will be shown to have no issues.
* It reinforces the image of a state-of-the-art, caring dental practice concerned for the oral and systemic health of it patients.
* It is affordable for patients, as practices can charge $15 or even less per screening.
* It can easily pay for itself in two months or less, and after that it can earn the practice $10,000-to-$20,000 in extra profit each year.
* Most important, it just might help you save a patient’s life.

In addition, LED Dental has a comprehensive education program for practices that are considering purchasing the VELscope Vx, and an extensive training program for practices that have purchased the system.

Every day of their careers, hygienists provide a variety of very important services for their patients. Now those patients are potentially vulnerable to a very serious health threat, and many of those patients have no idea that this threat exists. And, as a result, hygienists now have an opportunity to have a more profound impact on the health and lives of their patients than ever before.

Source: DentistryIQ

April, 2011|Oral Cancer News|

AAOMS Supports Goals of Oral Cancer Awareness Week

ROSEMONT, Ill., April 1, 2011 /PRNewswire-USNewswire/ — The 2011 Oral Cancer Awareness Week, set for April 11-15, is intended to educate people of all ages and socio-economic levels about the risk factors and symptoms of oral, head and neck cancer and the importance of early detection. The American Association of Oral and Maxillofacial Surgeons (AAOMS) agrees with the Oral Cancer Foundation, which conceived the awareness week observance, that it is critical oral cancers receive the national media attention necessary to raise public awareness.

The Oral Cancer Foundation points out that the high death rate traditionally associated with oral cancer is not because it is hard to discover or diagnose, but because the cancer has historically been discovered late in its development.  In its early stages, oral cancer may – and often does – go unnoticed because there are no blatant symptoms or pain.  This only underscores the importance of establishing a regimen to include regular self-examinations and examination by a dentist or oral and maxillofacial surgeon at least annually.

The mouth is one of the easiest parts of your body to examine yourself. Also, changes in the mouth can be easily seen, so oral cancer can be detected in its early stages. The key to early detection is performing a self-examination regularly. Examining your mouth each month will help you identify changes or new growths early. And, early detection is important in increasing the chance of a cure.

Factors That May Cause Cancer

According to the National Institutes of Health, approximately 35,000 people will be diagnosed with oral cancer each year.  The disease will strike two men for every woman, and will occur twice as often in the African American community.

Research has identified a number of factors that may lead to oral cancer. Of these, lifestyle choices, including use of tobacco and alcohol, remain the biggest cause of oral cancer. Other common factors include poor oral hygiene, irritation caused by ill-fitting dentures and rough surfaces on teeth, poor nutrition, some chronic infections and combinations of these factors. And, in recent years, the sexually transmitted HPV16 virus has been a rising factor in oral cancer, especially among younger adults. It is important to note, however, that about 25% of oral cancer patients have no known risk factors.

Studies have shown that the death rate from oral cancer is about four times higher for cigarette smokers than for nonsmokers. Those who both drink alcohol and smoke are 15 times more likely to develop the disease than those who engage in only one of these activities.

It is widely believed in the medical field that the heat generated by smoking pipes and cigars irritates the mouth and can lead to lip cancer. Prolonged sun or tanning bed exposure also puts you at risk for lip cancer.

Those at an especially high risk of developing oral cancer are over 40 years of age, heavy drinkers and smokers, or users of smokeless tobacco, including snuff. However, the number of people under 40 who have been diagnosed with oral cancer has been increasing.

Perform a Self-Exam Monthly

Oral and maxillofacial surgeons recommend that everyone perform an oral cancer self-exam each month. If you are at high risk for oral cancer — smoker, consumer of alcohol, user of smokeless tobacco, or snuff — you should also see your general dentist or oral and maxillofacial surgeon for an annual exam.

Visit the media page at aaoms.org for tips on how to perform a self-examination and what to look for.

Saving Faces, Changing Lives® — The American Association of Oral and Maxillofacial Surgeons (AAOMS), the professional organization representing more than 9,000 oral and maxillofacial surgeons in the United States, supports its fellows’ and members’ ability to practice their specialty through education, research and advocacy. AAOMS fellows and members comply with rigorous continuing education requirements and submit to periodic office examinations, ensuring the public that all office procedures and personnel meet stringent national standards.

SOURCE American Association of Oral & Maxillofacial Surgeons

We owe it to our sons to protect them against human papilloma virus – the new oral cancer peril

Source: www.dailymail.co.uk
Author: Professor Lawrence Young

The seemingly unstoppable rise of throat and mouth cancers over the past two decades has left experts baffled and deeply concerned. These are truly horrible diseases. More than 15,000 new patients are diagnosed each year in Britain alone and almost 8,000 die from the most common type, cancer of the oesophagus. Two-thirds of sufferers are men. And those that survive are often left horrifically disfigured by aggressive radiotherapy and surgery. Most worryingly, numbers of new cases have doubled since 1989.

We used to think most oral and throat cancers – which also include laryngeal (voice box), tracheal (windpipe) and oropharyngeal (soft-palate) tumours – were due to a lifetime of smoking and heavy alcohol consumption, and only really occurred in old age. But as health messages hit home, numbers of smokers and drinkers dropped, fewer older men and women developed these cancers and a new group of patients – middle-class, middle-aged men who drank moderately and had never smoked – emerged. This was a surprise.

Threat: Small studies, in which oral cancer tumours were analysed, reveal a new culprit: the human papilloma virus

Small studies, in which tumours were analysed, indicated a new culprit: the human papilloma virus (HPV), the same virus that we knew was the cause of cervical cancer in women. For years there have been whisperings among oncologists that this could become one of the most significant cancer challenges of the 21st Century. And six weeks ago, evidence published by two American universities showed that these fears were becoming a reality.

Researchers found that about half of the male population carried some form of HPV; that every year there is a six per cent increase in carriers of HPV 16 and 18 – the deadliest forms of the virus; and that up to 64 per cent of head and neck cancers are likely to be caused by the virus.

HPV is an umbrella term for about 200 strains of virus. More than 40 types are transmitted through sexual contact. Some cause genital warts but most men and women who catch HPV never develop symptoms. I was involved in early screening studies that linked the virus to gynaecological cancers in women. Now I implore health chiefs to think seriously about vaccinating boys against HPV.

Since 2008, British girls between the ages of 12 and 13 been given the HPV vaccine Cervarix, which protects against HPV 16 and 18. Initially the programme was met with disdain – it was claimed that giving the vaccine would sexualise prepubescent girls. But it needs to be administered as early as possible before the onset of sexual activity as exposure to any strain of the virus renders the vaccine ineffective.

Some might think that vaccinating women is enough, but while teenage girls are supposed to be given the vaccine, there is no law to ensure every girl has it. Even optimistic figures put the amount of British girls having the jab at just 70 to 80 per cent. Furthermore, there has not been enough research about how HPV is transmitted from women to men – we still aren’t entirely sure if the vaccine stops a woman being able to carry the virus, even if she has been made immune to the effects of it.

Yes, sex has played a role in increasing the number of HPV-related cancers – it is incredibly difficult to transmit the virus without having sexual contact. Fifty years ago, sex before marriage was frowned upon and multiple partners were unusual. HPV can be transmitted from a woman to the mouth and throat of a man during oral sex. But this does not equate with promiscuity.

Carriers of HPV 16 or 18 can show no symptoms for many years before the cancer develops, so it is entirely possible to have just one sexual partner and contract the virus without even knowing it. The only thing that stands in the way of combating this deadly threat is funding. Currently the vaccine is not available for boys in the UK – neither on the NHS, nor privately. This, in my opinion, needs rethinking.

In the US, parents are already paying privately to get their sons vaccinated. The NHS is under huge financial stress and the announcement of £1billion in cuts turns a blanket vaccination for all British boys into a costs issue that must be debated. Adults cannot be vaccinated – for us, regular check-ups and limiting sexual partners are the only options. Once contracted, there is no way to get rid of HPV, although we hope to develop treatments. For the majority it won’t cause cancer.

More tests need to be done to fully understand how HPV is spread between men and women. And we need to demand, as parents, that our sons have the same right as their sisters in being protected against HPV.

April, 2011|Oral Cancer News|

Revealed: oral sex is ‘bigger cause of throat cancer than tobacco’

Source: www.dailymail.co.uk
Author: staff

A virus spread during oral sex is now the main cause of throat cancer in people under 50, scientists have warned. They say the human papilloma virus spread during unprotected sex is to blame for a disturbing rise in potentially deadly oral cancers in the last few decades.

Doctors have called for boys to be vaccinated against HPV just like teenage girls to stop the spread of the disease.

HPV is best known as the cause of around 70 per cent of cervical cancers. Since 2008, girls have been vaccinated against the virus aged 12 and 13 in schools. However, it can also cause warts, verrucas and other cancers. Cancers of the mouth and oropharynx – the top of the throat – used to be mainly diagnosed in older men who drink or smoke. But increasingly, it is being seen in younger men.

Prof Maura Gillison of Ohio State University in Columbus said the sexually transmitted HPV was a bigger cause of some oral cancers than tobacco.

She said: ‘We don’t know from strict scientific evidence whether the vaccine will protect from oral HPV infections that lead to cancer. Those of us in the field are optimistic it will – the vaccines in every anatomical site looked at so far have been shown to be extraordinarily effective, about 90 per cent effective, at preventing infections.’

‘When one of my patients asks whether or not they sound vaccinate their sons, I say certainly.’

Girls aged 12 and 13 are offered the HPV vaccine on the NHS to protect against cervical cancer – a disease that kills nearly 1,000 women every year in the UK. The jab is given at school in three doses over six months. Doctors are increasingly concerned that the sexually transmitted virus is behind a rise in cancer.

Worrying: the sexually transmitted HPV was a bigger cause of some oral cancers than tobacco. In Britain the incidence of throat cancer is rising sharply while in the US the incidence of oral cancers linked to HPV have doubled in the last 20 years. In Sweden in the 1970s around a quarter of tonsil cancers were linked to HPV, but by the mid 2000s the figure was 90 per cent said Prof Gillison.

‘That’s the most compelling data in a population that the increase in tonsular cancer or oropharynx cancer incidence we’re seeing in a number of places worldwide is possible caused by HPV,’ she said.

Someone infected with HPV 16 – the strain linked to oral cancer- has a 14 fold increase in risk for getting oropharynx cancer, she said.

She added: ‘What is most strongly linked to oral HPV infection is the number of sexual partners someone has had in their lifetimes, in particular the number of individuals on whom they have performed oral sex.

‘The higher the number of partners that you’ve had, the greater the odds that you’d have an oral infection.’

Yesterday, researchers told the American Association for the Advancement of Science conference in Washington CD that teenagers consider oral sex to be ‘casual, socially acceptable, inconsequential and significantly less risk to their health than “real” sex.’

Last year a study at Johns Hopkins University found that HPV posed a greater risk in contracting cancer than smoking or alcohol. The American study of 300 people showed that those with more than six partners were almost nine times at greater risk of contracting the disease while those who had already experienced a previous oral HPV infection were 32 times more likely to develop cancer.

Most HPV infections have no symptoms and people often do not need treatment. Sara Hiom, Cancer Research UK’s director of health information, said: ‘Cancers in the mouth and throat are on the increase and rates have been rising dramatically in the UK since the mid 1980s, especially in people in their 40s, 50s and 60s.

‘The proportion of these cancers that appear to be related to infection by HPV is also increasing. But while it’s reasonable to assume that HPV vaccination in girls and boys would protect against these cancers, there is as yet no evidence as to whether the current HPV vaccines are effective at preventing them. The trials done to date have looked at cervical cancer or genital warts as endpoints, so we need new studies to show effectiveness against these HPV-related head and neck cancers. Yet most oral cancers diagnosed in people over 50 in the UK are still related to tobacco and alcohol use.’

February, 2011|Oral Cancer News|

Quadrivalent HPV vaccine may be effective in young men

Source: www.medscape.org
Author: Laurie Barclay, MD; Charles P. Vega, MD

Quadrivalent human papillomavirus (HPV) vaccine may prevent infection with HPV types 6, 11, 16, and 18 and the development of related external genital lesions in young men 16 to 26 years old, according to the results of a randomized, placebo-controlled, double-blind trial reported in the February 3 issue of the New England Journal of Medicine.

“Infection with …HPV and diseases caused by HPV are common in boys and men,” write Anna R. Giuliano, PhD, from the Risk Assessment, Detection, and Intervention Program, H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, and colleagues. “We report on the safety of a quadrivalent vaccine (active against HPV types 6, 11, 16, and 18) and on its efficacy in preventing the development of external genital lesions and anogenital HPV infection in boys and men.”

The study sample consisted of 4065 healthy boys and men, aged 16 to 26 years, enrolled from 18 countries. The primary efficacy goal was to demonstrate that use of the quadrivalent HPV vaccine was associated with a lower incidence of external genital lesions related to HPV-6, 11, 16, or 18. The investigators used a per-protocol population, in which participants received all 3 vaccinations and had tested negative for relevant HPV types at enrollment, and an intent-to-treat population, in which participants received vaccine or placebo, regardless of baseline HPV status.

In the intent-to-treat population, there were 36 external genital lesions in the vaccine group and 89 in the placebo group, yielding an observed overall efficacy of 60.2% (95% confidence interval [CI], 40.8 – 73.8). Vaccine efficacy for lesions related to HPV types 6, 11, 16, or 18 was 65.5% (95% CI, 45.8 – 78.6). In the per-protocol population, the observed efficacy was 83.8% (95% CI, 61.2 – 94.4); for lesions related to HPV types 6, 11, 16, or 18, the efficacy was 90.4% (95% CI, 69.2 – 98.1).

Observed efficacy regarding persistent infection with HPV-6, 11, 16, or 18 was 47.8% (95% CI, 36.0 – 57.6) in the intent-to-treat population and 85.6% (97.5% CI, 73.4 – 92.9) in the per-protocol population. Efficacy regarding detection of related DNA at any time was 27.1% (95% CI, 16.6 – 36.3) and 44.7% (95% CI, 31.5 – 55.6), respectively.

Significantly more participants receiving quadrivalent HPV vaccine had injection-site pain vs those receiving placebo (57% vs 51%; P < .001).

“Quadrivalent HPV vaccine prevents infection with HPV-6, 11, 16, and 18 and the development of related external genital lesions in males 16 to 26 years of age,” the study authors write.

Limitations of this study include narrow age range of the participants and relatively short follow-up period. In addition, participants had no more than 5 lifetime sexual partners, which may have resulted in overrepresentation of participants with a low likelihood of HPV exposure at baseline and a low likelihood of subsequent exposure vs the general population.

In an accompanying perspective, Jane J. Kim, PhD, From the Department of Health Policy and Management at Harvard School of Public Health in Boston, Massachusetts, notes “the extraordinary potential for HPV vaccination to improve health in both women and men.”

“And although enthusiasm for universal vaccination may initially be tempered by uncertainties about the vaccine’s safety, efficacy, and duration of protection (as well as its uptake, acceptability, and cost), many of these factors could very well change in the future,” Dr. Kim writes. “For example, the cost-effectiveness profile of routine vaccination of young men will improve if the evidence of efficacy continues to mount, the vaccine price declines, or coverage among girls and women remains low. To maximize the benefits to the population’s health from health services and interventions, we have a responsibility to use resources as efficiently as possible.”

Merck, the National Center for Research Resources, and the National Institutes of Health supported this study. Merck employs 7 of the study authors and has disclosed various financial relationships with 5 other study authors. Some of the other study authors have disclosed various other financial relationships with GlaxoSmithKline, Qiagen, and/or AstraZeneca. Dr. Kim has disclosed no relevant financial relationships. Disclosure forms provided by the authors and by Dr. Kim are available with the full text of the journal article at the New England Journal of Medicine Web site .

Source: N Engl J Med. 2011;364:401-411. Abstract

February, 2011|Oral Cancer News|

HPV: To test or not to test

Source: www.rdhmag.com
Author: Nancy W. Burkhart, RDH, EdD

The dental practitioner has a responsibility to examine and assess the oral tissue status of all patients. Usually, we are happy to report that the tissue is healthy and no further treatment is necessary. Ethically, our role in assessment is both an understood practice as well as a legal one each time we interact with our patients.

Tonsillar cancer. Courtesy of: Dr. Martin T. Tyler, McGill University Health Center.

Within your practice, what is the expected role in assessing and relaying advice/recommendations to our patients? Do we rely strictly on scientific evidence with evidence-based protocol? Do we trust the developers/promoters of dental products to provide information to us? Do we relay personal opinion from colleagues, or do we reject opinion-based information? Do we search the scientific literature for current information, or call our colleagues and company representatives and obtain a consensus of what the best options may be for dissemination of information?

We have all been in these situations. With busy practices, it is very time consuming to sit down and evaluate all the literature. Anyone who has been faced with a medical decision for a loved one or ourselves may actually feel exhausted while trying to sort through all of the options, treatments, and advice – some of which may even be at odds within specific group specialties in the way treatment is rendered. It can be very daunting, draining us both mentally and physically. So how do we approach this dilemma?

For some time, we have known about the detrimental effects of alcohol and tobacco products and the role of both in the etiology of oral cancer. Counseling a patient on discontinuing these products has become commonplace. Most of the population knows that these products are detrimental, but we still try to provide both current and factual information to our patients. Recently, considerable information has been published about the human papillomavirus (HPV) status of the patient. Both hygienists and dentists are being asked about HPV (specifically HPV 16) and its connection to oral cancer. HPV has been correlated with cancer at the base of the tongue, the oropharynx, and tonsil. Although we know that the correlation is present and oral exams are performed periodically, these areas are difficult to assess and do not appear as the typical oral tissue changes that we have been able to detect during oral cancer exams. These cancers are not easily detected through visual exams, palpation in early development, and by using some of the early cancer detection devices on the market while in early stage. Most of these cancers are detected in a late stage because the tonsillar tissue, particularly the tonsillar crypts, have many crevices and tissue surfaces that are hidden from the practitioner’s view. Some individuals have disease states hidden in the tissues.

By the time the problem is observed and detectable changes are observed in the lymph nodes, the stage is much higher and usually at a Stage III or IV. Although it is so important to check the posterior areas of the mouth, it is not uncommon to find that tonsillar regions are neglected.

For many years, dentistry did not even consider this “their area of expertise or responsibility” and the examination was left to the medical community. Students now are taught to check this area thoroughly while in dental schools, and we now know that the tissue in this area of the mouth is highly linked to HPV. Because of the lack of clear visible oral lesions, the palpation of cervical lymph nodes and close examination of these areas is crucial.

An excellent oral exam video has been produced by Dr. Michael Siegel and Dr. Valerie Murrah (see references). Dr. Siegel and Dr. Murrah demonstrate the exam with a thorough focus on the cervical lymph nodes and the oropharynx.

What do we really know about HPV?
A recently published letter written by Dr. Mark W. Lingen (2010) addressed the issue associated with the saliva test that is being offered in dental offices with on-site training by representatives of the company manufacturing the test. In the paper, he states that it appears that this test “is a test looking for a disease.” He additionally questions whether knowing if one is HPV positive really means anything that is clinically significant for the patient.

Most of the time HPV is cleared from the body through its own immune system. If the person is tested again at a later date, the results in most cases will be negative. Some individuals who have ongoing positive results could be more susceptible to oral cancer.

Essentially, we really do not know very much as to how this entity behaves in all individuals. We cannot predict in whom the virus will persist.

Overall, we do know that some individuals are more susceptible to certain disease states and cancers. As an example, we know that some individuals in their eighties and nineties have smoked all their lives, and yet they do not develop oral or lung cancer. Why is one individual affected and not another? Clearly, there are multiple factors playing a role in the development of disease states, and this may be genetically and environmentally influenced. Dr. Lingen also suggests that those reading his article may want to peruse a published article by Dr. Jaeschke et al. on a user’s guide to the medical literature. It is instructive in how to use an article promoting a diagnostic test (see references).

With the continued rise of oral cancer in the under 40-year-old age group without known risk factors, what do we really know about HPV?

  • We know that we are seeing oral cancer in the younger age groups (under 40 years old) with no historic risk factors, such as tobacco and alcohol.
  • We are finding posterior of the mouth cancer at advanced stages with often occult primary lesions in the oropharynx, base of the tongue, and tonsillar tissue. Most of the time these do not produce the historic surface lesions we are accustomed to finding. Neck palpation for hard, painless, fixed nodes is becoming increasingly important as a component of the oral exam. The CDC estimates that 20 million Americans are currently infected with HPV. This number is constantly changing as new data becomes available.
  • 50% of sexually active adults will be infected with HPV in their lifetime.
  • The National Cancer Institute estimates 36,540 oral cancers in 2010 with 7,880 subsequent deaths within the United States. These numbers vary with some of the large research institutes conducting current research.

I recently presented a seminar on mucosal diseases at a national meeting and introduced some ideas of my own. I found that I really could not even answer my own questions based on the research I read. Consequently, I then turned to open dialogue with those whom I knew had studied the literature on the subject. Unfortunately, I was less clear after assessing the information than I was at the start of my search. If I was not completely clear, what would I tell patients or students who asked the following?

  • Does kissing transfer the HPV and make the other person susceptible to oral cancer? How much of a deep passionate kiss do you need to transfer the HPV? How would you even begin to test this assumption?
  • Is a child at risk if the mother is HPV positive?
  • Can HPV be transferred if the mother tastes her baby’s food before giving it to the child? Since this is a rather common practice, should we be concerned about contagion? This is always a question that a patient will ask when diagnosed with any disease state.
  • Is an HPV positive person more at risk if he/she uses tobacco and alcohol together? Or, is one more of a risk than the other? Is a person who may be genetically susceptible to cancer more affected by the trio of alcohol, tobacco, or HPV?
  • Is the HPV an entity that can be harbored for years and then reappear? If you are in a relationship, does this open up the questions of fidelity? And, how do you help the patient answer this question, or can you possibly provide any answers?
  • Do you test all patients, or just some known high-risk groups?
  • Do you check adolescents who may or may not admit to sexual activity? Do you talk to the parent first before even asking? What would be the reaction of a parent? As you know, adolescents and even some much older individuals do not consider oral sex to be “true” sex, so your phrasing and communication is crucial.
  • Do you recheck a positive patient again and at what intervals?
  • Who should talk with the patient? How confidential is the information?
  • Do you check the entire family for HPV? Do you check at intervals?
  • Do you test patients for HPV who have had a previous oral cancer at every appointment?
  • Does the constant bleaching of teeth (practiced by many under 40 years of age) affect the oral tissues in some individuals, and does HPV affect this tissue after or during bleaching?
  • Does GERD and frequent heartburn make the tissues more susceptible to HPV in some individuals – possibly those with a genetic predisposition?

Finding the answers to our questions about HPV
I have pondered these questions for several months now and discussed all these questions with many colleagues who have expertise in oral medicine and pathology. I don’t know the answers to these questions in the depth needed to make clear recommendations. Frankly, I am amazed at how fast the dental/dental hygiene community has embraced the addition of promoting HPV testing in the dental office without knowing the answers to many important questions related to HPV.

We must do our own critical thinking about new information and the ramifications of that information for our patients. It is clearly never a sound idea to automatically discount information because it is new and maybe not in line with our current thoughts or those of our trusted fellow professionals. Progress in research is based on innovation, analysis, and critical thinking.

I, for one, believe that we have in some ways lost touch with the promotion of innovation and critical thinking. They are intertwined. Most people who are in research and education have a strong innovative side and those people who go into specialty areas in dentistry often have an investigative/innovative side as well. So what are we to accept and to believe and how do we assess new information? And, when is there enough evidence-based information to suggest new protocol to our patients?

Steven Berlin Johnson, in his new book, “Where Good Ideas Start,” states that alcohol was used as a “cure all” in early English history. We know that there is a depressant effect to alcohol. As time progressed, it was found that the new coffeehouses in England provided not only the stimulant brew of coffee, but it was determined that the arousal of ideas was prevalent as well. I am not suggesting that we all drink coffee and sit around discussing our ideas, but open pathways for discussion are key.

This promotion of discussion and sharing ideas goes back to early years when Ben Franklin led discussion sessions and the “Junto Groups” of like-minded craftsmen and townspeople came together to discuss the topics of the day.

Any time you have a group of people who gather and discuss ideas, new information is shared and new ideas flourish. The Internet has provided the opportunity in which discussion board participants post questions, relevant ideas can be debated, and critical thinking is promoted. This is true for many of us in the dental community where it is so easy to accept ideas from others in our profession. But we need to raise these questions, listen to other views, and critically analyze information. The Internet has provided a sounding board where patients, researchers, practitioners, and family members come together, ask questions, and discuss areas of concern.

An Internet site and discussion board was founded by Brian Hill of the Oral Cancer Foundation, Inc., and Brian is an oral cancer survivor himself. His organization provides educational materials, lectures and discussion postings for those who have been diagnosed with oral cancer. The group also supports family members dealing with oral cancer.

Brian has been instrumental in calling attention to the screening process and the importance of the oral exam, along with its role in early detection. He has been instrumental in the discussion of the role of HPV in oral cancer and calling attention to the risk factors for oral cancer with the distribution of educational materials. The Web site for the foundation is: http://www.oralcancer.org“, and a section of the site is devoted to HPV.

It is interesting that so little time is spent trying to provide information on nutrition and lifestyle modifications that clearly impact the health of all patients. Yet, dental personnel are being asked to counsel patients about sexual practices and personal medical information with regard to HPV status. If we do provide this counseling, what are the long-term ramifications?

A phenomenon in the medical field is known as “white coat syndrome.” Patients experience and test very high for blood pressure readings when they enter a medical office. Cardiologists are aware of this phenomenon, even among regular patients. We know how powerful the mind is, and there is no doubt that some disease states can actually develop due to prolonged stress and are termed “health anxiety.” The mind-body connection is very strong. Are we really ready to deal with all the psychological problems that may develop in our patients when given test results for HPV status? And, as Dr. Lingen so eloquently stated, do we really have enough information and what do the results really mean anyway?

Lastly, are we creating more problems than we are attempting to solve? Asking questions, discussing issues, and assessing the evidence is always necessary.

Keep asking good questions and always listen to your patients!

Nancy W. Burkhart, BSDH, EdD, is an adjunct associate professor in the department of periodontics, Baylor College of Dentistry and the Texas A & M Health Science Center, Dallas. Dr. Burkhart is founder and co-host of the International Oral Lichen Planus Support Group http://www.bcd.tamhsc.edu/outreach/lichen/ and coauthor of General and Oral Pathology for the Dental Hygienist. Her Web site for seminars is www.nancywburkhart.com.

Burkhart, NW. Squamous cell carcinoma of the tonsil. RDH November 29:11 2009.
Johnson S. Where good ideas come from: The natural history of innovation. Riverhead Books, New York. 2010.
Lingen MW. Editorial in Oral Surg Oral Med Oral Pathol Oral Radiol Endod 110:3, Sept.2010.
Jaeschke R, Guyatt GH, Sackett DL. Users’ guides to the medical literature. III. How to use an article about a diagnostic test. What are the results and will they help me in caring for my patients? The Evidence-Based Medicine Working Group. JAMA 1994; 271:703-7.
Ryerson AB, Peters ES, Coughlin SS, Chen VW, Gillison ML, Reichman ME, Wu X, Chaturvedi AK, Kawaoka K. Burden of potentially human papillomavirus-associated cancers of the oropharynx and oral cavity in the US, 1998-2003. Cancer Nov 15:113 (10 suppl) 2901-9.
Siegel M , Murrah V, Aloise D. Head, Neck and Oral Cancer Examination. MedEdPORTAL; 2009. Available from: http://services.aamc.org/30/mededportal/servlet/s/segment/mededportal/?subid=7768.


High-risk human papillomavirus in esophageal squamous cell carcinoma

Source: cebp.aacrjournals.org
Authors: Annika Antonsson et al

Although most cases of esophageal squamous cell carcinoma (ESCC) in western populations have been attributed to high levels of exposure to tobacco and alcohol, infectious agents have been postulated as possible causes, particularly human papillomavirus (HPV).

To explore this issue, we analyzed HPV DNA prevalence and HPV types together with lifestyle factors, in relation to tumor stage and survival in a low-incidence population. Archived tumor samples from a nationwide cohort of 222 ESCC patients were tested for the presence of HPV DNA by PCR; positive samples were sequenced to determine HPV type, and p16INK4a status was assessed by immunohistochemistry.

Of 222 ESCC patients, 8 tested HPV positive (prevalence, 3.6%; 95% confidence interval, 1.1-6.1%), of which 6 were HPV-16 positive and 2 were HPV-35 positive. Four of the eight HPV-positive tumors overexpressed p16INK4a. None of 55 normal esophageal tissue samples from healthy participants had any detectable HPV. Although the numbers were low, it seemed that patients with HPV-positive ESCC tumors were younger than those with HPV-negative tumors (mean age, 60.8 versus 65.3 years, P = 0.18) and had higher body mass index (BMI) throughout life (mean current BMI of 25.1 for HPV positive, 22.2 for HPV negative, P = 0.08; mean BMI at 20 years of 25.8 for HPV positive, 22.1 for HPV negative, P = 0.003). We found no difference between patients with HPV-positive and HPV-negative tumors with respect to other lifestyle factors.

Conclusions: These findings suggest a very low prevalence of HPV DNA in human ESCC.

HPV is very unlikely to be a common cause of ESCC in Australia. Cancer Epidemiol Biomarkers Prev; 19(8); 20.

1. The Australian Cancer Study: Esophageal Cancer: Investigators: David C. Whiteman, Penelope M. Webb, Adele C. Green, Nicholas K. Hayward, Peter G. Parsons, David M. Purdie. Clinical collaborators: B. Mark Smithers, David Gotley, Andrew Clouston, Ian Brown. Project Manager: Suzanne Moore. Database: Karen Harrap, Troy Sadkowski. Research Nurses: Suzanne O’Brien, Ellen Minehan, Deborah Roffe, Sue O’Keefe, Suzanne Lipshut, Gabby Connor, Hayley Berry, Frances Walker, Teresa Barnes, Janine Thomas, Linda Terry, Michael Connard, Leanne Bowes, MaryRose Malt, Jo White.

2. Study of Digestive Health: Investigators: Queensland Institute of Medical Research, Brisbane Australia: David C. Whiteman, Adele C. Green, Nicholas K. Hayward, Peter G. Parsons, Sandra J. Pavey, David M. Purdie, Penelope M. Webb; University of Queensland, Brisbane, Australia: David Gotley, B. Mark Smithers; The University of Adelaide, Adelaide, Australia: Glyn G. Jamieson; Flinders University, Adelaide, Australia: Paul Drew, David I. Watson; Envoi Pathology, Brisbane, Australia: Andrew Clouston.

3. Research Staff: Project Manager: Suzanne O’Brien; Research Scientist: Derek Nancarrow; Research nurses: Andrea McMurtrie, Linda Terry, Michael Connard, Deborah Roffe, Lorelle Smith, Marian Martin, Jeanette Mayhew, Susan Perry, Marcia Davis.

Annika Antonsson1, Derek J. Nancarrow2, Ian S. Brown3, Adele C. Green1, Paul A. Drew4, David I. Watson5, Nicholas K. Hayward2 and David C. Whiteman1 for the Australian Cancer Study1

Authors’ affiliations:
1Genetics and Population Health Division and 2Oncogenomics, Queensland Institute of Medical Research, and 3Sullivan Nicolaides Pathology and Royal Brisbane and Women’s Hospital Brisbane, Brisbane, Queensland, Australia; 4School of Nursing and Midwifery, and 5Department of Surgery, Flinders University, Bedford Park, South Australia, Australia

August, 2010|Oral Cancer News|

Human papilloma virus (HPV) and cancer

Source: ezinearticles.com
Author: David Warmflash, MD

Human papilloma virus (HPV), is a category of viruses of which more than seventy subtypes are known. Most people have heard of HPV, because the media have spent a good deal of time discussing the issue of mandatory vaccination against the virus. The discussion in the news is well-deserved. Each year, approximately 6.2 million people are infected with (HPV). Usually, the virus is cleared by the immune system, before any disease can develop.

However, because of the high rate of infection, HPV-associated disease is all-too common around the world. Each year 11,000 new cases of invasive cervical cancer are diagnosed in the United States, leading to approximately 4,000 deaths. The rate would be much higher, were it not for the advent of the the Papanicolaou test (Pap smear), used to screen for precancerous conditions since the 1930s. Since Pap smears and HPV vaccinations are hot topics, even if you have no background in medicine, it is likely that you are aware of HPV as an agent that causes cervical cancer. What you may not know, however, is that HPV also is involved in cancers of the throat and the skin.

Actually, not all of the subtypes of HPV are known to be involved in the pathological process leading to cancer and precancerous conditions of the cervix. Of the HPV subtypes linked to cervical cancer, four types are most important. These are HPV-6b, HPV-11, HPV-16, and HPV-18, the latter two being the most dangerous for women, because they are found in a high percentage (60-80%) of the high-grade lesions that lead cancer if not removed, and 90% of the cancers that invade from the cervix to other parts of the body. Although less important in the development of cervical cancer, subtypes 6b and 11 cause genital warts.

Thus, one of the two vaccines licensed by the Food and Drug Administration (FDA) to prevent the spread of HPV in the United States, Gardasil, works against HPV types 6b and 11 as well as types 16 and 18. Since genital warts affects males as well as females, the Advisory Committee on Immunization Practices (ACIP) of the Center for Disease Control (CDC) has recommended this vaccine for both sexes. The other licensed vaccine, Cervarix, is recommended for females. These recommendations, however, may change eventually, since studies in recent years have revealed that HPV causes disease not only in the genitals but elsewhere in the body.

In Texas, Executive Order 4 mandated HPV vaccination for 6th grade girls. While this was overturned by the Texas legislature, Virginia and the District of Columbia now require HPV vaccination with Gardasil or Cervarix for girls from age 11. Parents are allowed to opt out, however, and in the case of Virginia without submission of signed waivers. Thus, in Virginia, the state public health department has no way to know for certain how many girls actually receive the vaccine. Currently, legislation seeking mandatory vaccination for girls, but not boys, is pending in several other states.

Opponents of mandatory HPV vaccination for girls note the success of secondary prevention of cervical cancer, namely early detection by PAP smear. When detected early, however, the pre-cancerous condition must be treated, often by procedures such as loop electrosurgical excision (LEEP), cryotherapy, laser therapy, or conization. This has implications in patient well-being, making primary prevention (preventing the disease process from beginning in the first place) more attractive.

Those favoring mandatory vaccination for girls but opposing it for boys cite low benefit/cost ratios, but this assumes most girls actually get the vaccine and ignores data which suggest that males as well as females can develop HPV-associated throat cancer as a result of oral sex. Also cited by opponents of mandatory HPV vaccination are concerns that private, for-profit manufacturers influence lawmakers by inflating the need for the vaccine.

For several years, it has been known that HPV causes warts in the upper respiratory tract, a condition known as respiratory papillomatosis. Then a few years ago, a very strong association was found between HPV-16 and oropharyngeal squamous cell carcinoma (OPSCC) – throat cancer. Naturally, it was thought that HPV could be spread by way or oral sex, and this turned out to be true. A study by the National Cancer Institute (NCI) found the incidence of OPSCC to be high in people with more than twenty-five life time sex partners, but with only six or more life time oral sex partners.

While it is true that smokers have a higher incidence of both cervical cancer and throat cancer, in the association between OPSCC and HPV-16 was found to be particularly high for non-smokers. This is to say that assuming you’re not foolish enough to smoke, the only way you’ll get throat cancer is by way of exposure to HPV, and specifically type-16 one of the types that causes cervical cancer. Based on this, it seems likely that the CDC eventually will recommend the Cervarix vaccine for males as well for females. But this is not the end of the HPV story. Recently, it was discovered that HPV also is associated with one type of skin cancer.

Earlier this month, a study was published in the British Medical Journal showing that HPV plays a causative role in the generation of squamous cell carcinoma of the skin. Though not nearly as dangerous as malignant melanoma, squamous cell carcinoma is the second most common type of skin cancer, behind basal cell carcinoma. If the term “squamous cell” sounds familiar, it may be because I mentioned it above, discussing OPSCC, a squamous cell carcinoma of the throat.

Squamous cells are a subtype of a cell type known as epithelial cells. Squamous epithelial cells form linings, such as the outer layer of the skin, the lining of inner body surfaces, like the throat, and -you guessed it-the lining of the cervix; cervical cancer also is a carcinoma of squamous epithelial cells. And so, it should be no surprise that the same type of virus -HPV- causes cancers in three different body parts.