National Cancer Institute

e-Cigarette Use Tied to Tobacco Use in Teenagers

Author: Diana Swift

e-Cigarette smoking appears to promote progression to traditional cigarette smoking and may be helping form a new population of smokers, according to a prospective study published online September 8 in JAMA Pediatrics.

Brian A. Primack, MD, PhD, from the Division of General Internal Medicine, University of Pittsburgh School of Medicine in Pennsylvania, and colleagues analyzed data on 694 young nonsmokers who were attitudinally nonsusceptible to smoking at baseline. The very small proportion (2.3%) who already used e-cigarettes at baseline proved more likely to progress to smoking or to being open to it.

The cohort, which was more than 75% non-Hispanic white, consisted of 374 females. The mean age of the 16 baseline e-cigarette users was 19.5 years compared with 20 years for nonusers.

Study data came from waves 2 and 3 of the US-based Dartmouth Media, Advertising, and Health Study, a national survey of adolescents and young adults aged 16 to 26 years who were recruited via random digit dialing using landline (66.7%) and cellular (33.3%) telephone numbers.

The survey, conducted from October 1, 2012, to May 1, 2014, started tracking e-cigarette use at wave 2 (2012 – 2013), which served as the baseline, whereas wave 3 (2013 – 2014) served as follow-up for the current study.

Eligible participants had to be never-smokers and attitudinally nonsusceptible to smoking at baseline. This was assessed with these questions: “If one of your friends offered you a cigarette, would you try it?” and “Do you think you will smoke a cigarette sometime in the next year?” Response options included “definitely yes,” “probably yes,” “probably no,” and “definitely no.” Those who responded “definitely no” to both measures were considered nonsusceptible nonsmokers.

After a year, 11 of 16 baseline e-cigarette users (68.8%) and 128 of 678 participants nonusers (18.9%) progressed to traditional combustible cigarette smoking. After controlling for demographic covariates such as age, sex, and maternal education level, baseline e-cigarette use was independently associated with both progression to smoking (adjusted odds ratio [AOR], 8.3; 95% confidence interval, 1.2 – 58.6) and progression to susceptibility (AOR, 8.5; 95% CI, 1.3 – 57.2) among initially nonsusceptible nonsmokers.

“These findings support regulations that decrease the accessibility and appeal of e-cigarettes to nonsmoking adolescents and young adults,” Dr Primack and associates write.

Conceding that some might see the small percentage of baseline e-smokers as not translating into a substantial public health risk, the researchers caution that e-cigarette use is on the rise. “[D]ata published in 2015 suggest that large numbers of youth are initiating e-cigarette use and that as many as half of these individuals do not smoke traditional combustible cigarettes. Therefore, it will be important to continue surveillance among youth of both e-cigarette use and overlap with use of other tobacco products.”

Noting that many youth may be dual users of cigarettes and e-cigarettes, the authors say nicotine exposure may drive initial e-cigarette users to use cigarettes as a more efficient nicotine delivery device. In addition, nicotine content aside, “e-cigarettes may behaviorally accustom individuals to powerful cigarette smoking cues such as inhalation, exhalation, and holding the cigarette.”

Furthermore, e-cigarettes, which expose users to potentially harmful aerosolized substances other than nicotine, are not subject to regulations limiting cigarette smoking, such as age limits for sale, flavoring and marketing restrictions, clean air laws, taxes, and labeling requirements, which may increase their accessibility to youth. “For example, e-cigarettes are marketed on television, representing the first time in more than 40 years that a smoking-related device is advertised on this medium,” the investigators write.

In an accompanying editorial, Jonathan D. Klein, MD, MPH, an adolescent medicine specialist and an associate executive director of the American Academy of Pediatrics in Elk Grove Village, Illinois, noted that a recent Centers for Disease Control and Prevention report found that e-cigarette use in the National Youth Tobacco Survey increased from 4.5% in 2011 to 13.4% in 2014, affecting more than 2.2 million students. “The article by Primack et al is one more piece of evidence that the effect of e-cigarettes on youth is happening now in real time,” he writes, adding that “these data provide strong longitudinal evidence that e-cigarette use leads to smoking, most likely owing to nicotine addiction.”

Dr Klein also points to mounting concerns among health experts that e-cigarettes will also renormalize smoking, delay or prevent cessation, and cause former smokers to become re-addicted. He says the evidence suggests that e-cigarette users are less likely to quit smoking traditional cigarettes than nonusers In spite of such data and evidence of harm from e-smoking devices. He states that the US Food and Drug Administration has failed to assert authority and oversight over these alternative products.

“We do not need more research on this question; we have the evidence base, and we have strategies that work to protect nonsmokers from e-cigarettes and other forms of tobacco,” Dr Klein writes. “What we still need is the political will to act on the evidence and protect our youth.”

This study was supported by grants from the National Cancer Institute and the National Center for Advancing Translational Sciences. The authors and Dr Klein have disclosed no relevant financial relationships.

JAMA Pediatr. Published online September 8, 2015. Article full text, Editorial full text

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

February, 2016|Oral Cancer News|

NCI-designated Cancer Centers Urge HPV Vaccination for the Prevention of Cancer

Author: Washington University School of Medicine in St. Louis Staff

Approximately 79 million people in the United States are currently infected with a human papillomavirus (HPV) according to the Centers for Disease Control and Prevention (CDC), and 14 million new infections occur each year. Several types of high-risk HPV are responsible for the vast majority of
cervical, anal, oropharyngeal (middle throat) and other genital cancers. The CDC also reports that each year in the U.S., 27,000 men and women are diagnosed with an HPV-related cancer, which amounts to a new case every 20 minutes. Even though many of these HPV-related cancers are preventable with a safe and effective vaccine, HPV vaccination rates across the U.S. remain low.

Together we, a group of the National Cancer Institute (NCI)- designated Cancer Centers, recognize these low rates of HPV vaccination as a serious public health threat. HPV vaccination represents a rare opportunity to prevent many cases of cancer that is tragically underused. As national leaders in cancer research and clinical care, we are compelled to jointly issue this call to action.

According to a 2015 CDC report, only 40 percent of girls and 21 percent of boys in the U.S. are receiving the recommended three doses of the HPV vaccine. This falls far short of the goal of 80 percent by the end of this decade, set forth by the U.S. Department of Health and Human Service’s Healthy People 2020 mission. Furthermore, U.S. rates are significantly lower than those of countries such as Australia (75 percent), the United Kingdom (84-92 percent) and Rwanda (93 percent), which have shown that high vaccination rates are currently achievable. The HPV vaccines, like all vaccines used in the U.S., passed extensive safety testing before and after being approved by the U.S. Food and Drug Administration (FDA). The vaccines
have a safety profile similar to that of other vaccines approved for adolescents in the U.S. Internationally, the safety of HPV vaccines has been tested and approved by the World Health Organization’s Global Advisory Committee on Vaccine Safety. CDC recommends that boys and girls receive three doses of HPV vaccine at ages 11 or 12 years. The HPV vaccine series can be started in preteens as early as age 9 and should be completed before the 13th birthday. The HPV vaccine is more effective the earlier it is given; however, it is also recommended for young women until age 26 and young men until age 21.The low vaccination rates are alarming given our current ability to safely and effectively save lives by preventing HPV infection
and its associated cancers. Therefore, we urge parents and health care providers to protect the health of our children through a number of actions:

  • We encourage all parents and guardians to have their sons and daughters complete the 3-dose HPV vaccine series before the 13th birthday, and complete the series as soon as possible in children aged 13 to 17. Parents and guardians should talk to their health care provider to learn more about HPV vaccines and their benefits.
  • We encourage young men (up to age 21) and young women (up to age 26), who were not vaccinated as preteens or teens, to complete the 3-dose HPV vaccine series to protect themselves against HPV.
  • We encourage all health care providers to be advocates for cancer prevention by making strong recommendations for childhood HPV vaccination. We ask providers to join forces to educate parents/guardians and colleagues about the importance and benefits of HPV vaccination. HPV vaccination is our best defense in stopping HPV infection  in our youth and preventing HPV-related cancers in our communities. The HPV vaccine is CANCER PREVENTION. More information is available from the CDC.

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


February, 2016|Oral Cancer News|

Federal goal is set to increase the amount of boys and girls vaccinated against HPV by 2020

Source: www. (Wall Street
Author: Caitlin McCabe

Public-health officials are pushing for higher HPV vaccination rates amid growing evidence that cancers linked to the virus are afflicting more men.

The National Cancer Institute announced recently it is pouring nearly $2.7 million into 18 U.S. cancer centers to boost HPV vaccinations among boys and girls. The cancer centers will work with local health clinics to set recommendations for vaccinating against the sexually transmitted infection, which in some cases can cause cancers in men and women later in life.

HPV, or human papillomavirus, was considered a women’s-only issue, after researchers discovered a link between it and cervical cancer in the 1980s. 

Now, as cervical-cancer rates are falling and oral-cancer rates in men steadily rise, “the burden of HPV cancer is shifting to men,” said Maura Gillison, a professor in the College of Medicine at Ohio State University Comprehensive Cancer Center.

Vaccination rates remain stifled, despite the availability of two vaccines that experts say provide effective coverage against cancer. 

The Department of Health and Human Services’ goal is to boost HPV-vaccination rates to 80% by 2020—which is far higher than the 38% of girls and 14% of boys who completed the three-dose HPV vaccine last year, according to data from the National Immunization Survey of teenagers.

Pediatricians say boosting those rates can be difficult. Pediatricians may feel uneasy talking to parents of young children about sexually transmitted infections, health experts say, while parents may resist the vaccine because they believe their child isn’t at risk.

“Discussing this vaccination is difficult because there’s an implication of sexual activity,” said Carrie Byington, a practicing pediatrician in Salt Lake City and chairwoman of the Committee on Infectious Diseases for the American Academy of Pediatrics. “It can make some pediatricians uncomfortable with the topic.”

A study conducted in 2011 by the Moffitt Cancer Center in Tampa, Fla., found fewer than 15% of physicians always recommended the vaccine to boys, and no more than 55% always recommended it to girls. Susan Vadaparampil, a professor in the department of oncologic services at Moffitt who helped lead the study, said she thinks recommendation rates have risen today but there’s a long way to go.

To ease difficult conversations, Dr. Vadaparampil said resources on the Centers for Disease Control and Prevention website suggests that pediatricians should emphasize the vaccine is ultimately a protection against cancer and explain why children should receive the shots at such a young age. 

Experts recommend the vaccine at age 11 or 12, but it can be given to girls up to age 26 and boys up to age 21. It is important for children to receive all three doses of the vaccine before they become sexually active.

“There’s science behind giving it at age 11—it’s not just about moral or family choices, or a child’s choice for sexual debut,” said Wendy Sue Swanson, a pediatrician and executive director of digital health at Seattle Children’s Hospital. “The immune response is better if you give it to an 11-year-old.”

Administering the vaccine at a young age doesn’t encourage sexual activity, Dr. Swanson said, citing a concern some parents have. A 2012 study comparing girls who had been vaccinated at ages 11 and 12 to nonvaccinated girls showed the vaccine made no difference in sexual behavior for at least three years after receiving the doses.

Not all cases of HPV are cancerous. Experts estimate nearly 79 million Americans are currently infected with one of the 100 different strains of HPV, which is passed via sex. 

Typically, a body’s immune system fights off HPV naturally within two years of exposure. Complications, such as genital warts or cancer, arise when the virus lingers. 

About 26,800 Americans are diagnosed with HPV-related cancers each year, about two-thirds of whom are women, according to 2010 data, the latest available, from the CDC.

The largest HPV-related threat to men is throat cancer, which has grown sharply in the past decade, Dr. Gillison said. 

Today, more than 90% of all oral cancers are HPV-related, according to trends Dr. Gillison has observed in clinical settings in developed countries. That is up from about 72% between 2000 and 2004 and 16% between 1984 and 1989, she said, referencing a study she conducted that analyzed throat tumors in the U.S.

Most of that growth has been in men: Each year, about 7,200 American men are diagnosed with HPV-related oral cancer, versus 1,800 cases in women, according to 2010 CDC data. 

Dr. Gillison said researchers estimate that around 2020, HPV-related oral cancers in men will eclipse cervical cancer, which afflicts some 12,000 new women each year, according to 2014 data from the American Cancer Society.

It’s unclear why men are more at risk for oral cancer than women, though some researchers suggest a person’s number of sexual partners may be related. The rise is problematic, Dr. Gillison said, because no preventive screening against throat cancer exists. 

“The problem with HPV-positive oral cancer is that premalignant lesions are not clinically detectable. They’re deep within the tonsils that are in the base of the tongue,” Dr. Gillison said. “By the time HPV-infection is detected, they usually already have Stage 3 or 4 cancer.”

That is why doctors and experts are relying so heavily on vaccination as prevention.

Two vaccines—Cervarix, manufactured by GlaxoSmithKline Inc., and Gardasil, manufactured by Merck & Co.—are currently available, though only Gardasil is usually recommended for boys.

Cervarix offers protection against two strains of HPV; Gardasil against four. A third vaccination from Merck currently awaiting approval from the Food and Drug Administration would offer protection against an additional five strains of HPV—nine in total. Doctors expect approval within in the next several months.


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

November, 2014|Oral Cancer News|

Oropharyngeal cancer patients with HPV have a more robust response to radiation therapy


(SACRAMENTO, Calif.) — UC Davis cancer researchers have discovered significant differences in radiation-therapy response among patients with oropharyngeal cancer depending on whether they carry the human papillomavirus (HPV), a common sexually transmitted virus. The findings, published online today in The Laryngoscope Journal, could lead to more individualized radiation treatment regimens, which for many patients with HPV could be shorter and potentially less toxic.

HPV-related cancers of the oropharynx (the region of the throat between the soft palate and the epiglottis, including the tonsils, base of tongue and uvula) have steadily increased in recent years, according to the National Cancer Institute, especially among men. At the same time, the incidence of oropharyngeal cancers related to other causes, such as smoking or alcohol consumption, is declining. HPV is the most common sexually transmitted infection in the United States; it can spread through direct skin-to-skin contact during vaginal, anal and oral sex.

The UC Davis study, conducted by Allen Chen, associate professor in the UC Davis Department of Radiation Oncology, examined patterns of tumor reduction during radiation treatment in two otherwise similar groups of patients with oropharyngeal cancer: those who tested positive for HPV and those who tested negative for the virus. None of the HPV patients in the study was a smoker, a leading risk factor for the disease.

Chen used CT scans acquired during image-guided radiation therapy (IGRT) and endoscopy (a tube with a small camera) to capture 3D images of the patients’ tumors and monitor their treatment progress. He found that within the first two weeks after starting radiation, the gross tumor volume decreased by 33 percent in HPV-positive patients, while the volume decreased by only 10 percent in HPV-negative patients.

Chen said the results demonstrate that HPV-positive patients have a more rapid and robust response to radiation treatments, confirming what clinicians have suspected for years.

“These HPV-related tumors literally melt before your eyes,” he said. “It is very gratifying to tell patients early on during treatment that their tumors are responding so quickly. Most of them are pleasantly relieved to hear such news.”

The rapid rate of tumor regression did not continue, however, after the second week of radiation treatment, and by the end of the seven-week regimen, the total tumor shrinkage in both groups of patients was nearly the same.

However, “the dramatic early response observed in the HPV-positive patients strongly implies that these tumors behave distinctly from a biological standpoint and could be approached as a separate disease process,” Chen said.

For example, the findings suggest that treatment for HPV-positive cancer may not need to be as intensive for it to be effective, Chen said, adding that a shorter, abbreviated treatment regimen would potentially lessen the side effects from radiation, which include sore throat, dry mouth, taste loss and swallowing difficulties.

“It is likely that treatment in the future will be individualized based on biomarkers present in the tumor, and HPV has the potential to do just that,” said Chen.

Chen said there is increasing evidence that HPV-positive patients who receive radiation treatments live longer and have higher cure rates. According to the NCI, 88 percent of the HPV-positive patients are still alive two years after their treatments, compared with 66 percent of the HPV-negative patients.

“Given the impressive outcomes for patients with HPV-positive cancer using currently aggressive treatments, how to de-intensify therapy while maintaining cure rates is definitely a hot topic right now,” said Chen.

Chen, in collaboration with colleagues, has recently launched a clinical trial of HPV-positive oropharyngeal cancer patients to evaluate outcomes when their radiation doses are reduced from seven weeks to either five or six, depending on their response to initial chemotherapy. This institutional trial, which is only available at UC Davis, just recently opened enrollment.

“Why subject a patient to seven weeks of radiation when five weeks of radiation could be just as effective?” Chen said. “Sparing select patients from this extra radiation could potentially prevent significant toxic side effects and improve quality of life, both in the short-term and long-terms.”

The current clinical trial also involves collection of oropharyngeal patient blood and tumor samples during treatment, so that researchers can precisely correlate HPV in these specimens with a patient’s rate of response to radiation therapy.

The dramatic increase in oropharyngeal cancers in recent years has been described as an “epidemic,” Chen said, due in large part to the increasing prevalence of HPV. In the United States, more than half of cancers currently diagnosed in the oropharynx are linked to HPV-16, according to the National Cancer Institute.

“Our trial was designed to help determine what the optimal treatment approach for these patients might be in the future,” Chen said.

Why HPV-positive tumors respond differently to radiation treatment is under investigation at UC Davis, as well. The thought is that HPV labels cancer cells with a foreign antigen, which stimulates an immune response, Chen said.

“The HPV hijacks the host cancer cell leading to expression of a viral antigen on the surface, causing the patient’s immune system to ramp up and fight the cancer,” Chen said. “By identifying which molecular pathways are up-regulated or down-regulated during radiation therapy, it is our hope that insight may be gained into why HPV-positive oropharyngeal cancer is so radiation sensitive. This could have tremendous implications for developing strategies to fight not just oropharyngeal cancer, but all tumors in the future.”



Other authors were Judy Li and Laurel A. Beckett from the Division of Biostatistics of the Department of Public Health Sciences, Talia Zhara of the Department of Radiation Oncology, Gregory Farwell of the Department of Otolaryngology-Head and Neck Surgery, Derick H. Lau, associate professor of internal medicine, hematology and oncology, Regina Gandour-Edwards of the Department of Pathology and Laboratory Medicine, Andrew T. Vaughan, professor of radiation oncology, and James A. Purdy professor emeritus of the Department of Radiation Oncology and former director of the physics division.

UC Davis Comprehensive Cancer Center is the only National Cancer Institute-designated center serving the Central Valley and inland Northern California, a region of more than 6 million people. Its specialists provide compassionate, comprehensive care for more than 9,000 adults and children every year, and access to more than 150 clinical trials at any given time. Its innovative research program engages more than 280 scientists at UC Davis, Lawrence Livermore National Laboratory and Jackson Laboratory (JAX West), whose scientific partnerships advance discovery of new tools to diagnose and treat cancer. Through the Cancer Care Network, UC Davis collaborates with a number of hospitals and clinical centers throughout the Central Valley and Northern California regions to offer the latest cancer care. Its community-based outreach and education programs address disparities in cancer outcomes across diverse populations. For more information, visit

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

September, 2012|Oral Cancer News|

Robotic Surgery Through The Mouth Safe For Removing Tumors Of The Voice Box, Study Shows


COLUMBUS, Ohio – Robotic surgery though the mouth is a safe and effective way to remove tumors of the throat and voice box, according to a study by head and neck cancer surgeons at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).

<p>Dr. Enver Ozer<br /></p>

Dr. Enver Ozer

This is the first report in the world literature illustrating the safety and efficacy of transoral robotic surgery for supraglottic laryngectomy, the researchers say.
The preliminary study examined the outcomes of 13 head and neck cancer patients with tumors located in the region of the throat between the base of the tongue and just above the vocal cords, an area known as the supraglottic region.
The study found that the use of robot-assisted surgery to remove these tumors through the mouth took about 25 minutes on average, and that blood loss was minimal – a little more than three teaspoons, or 15.4 milliliters, on average, per patient. No surgical complications were encountered and 11 of the 13 patients could accept an oral diet within 24 hours.
If, on the other hand, these tumors are removed by performing open surgery on the neck, the operation can take around 4 hours to perform, require 7 to 10 days of hospitalization on average and require a tracheostomy tube and a stomach tube, the researchers say.
The findings were published recently in the journal Head and Neck.
“The transoral robotic technique means shorter surgery, less time under anesthesia, a lower risk of complications and shorter hospital stays for these patients,” says first author Dr. Enver Ozer, clinical associate professor of otolaryngology at the OSUCCC – James.
“It also means no external surgical incisions for the patient and better 3-D visualization of the tumor for the surgeon,” says Ozer, a head and neck surgeon who specializes in robot-assisted techniques.
The cases examined in this study were part of a larger prospective study of 126 patients undergoing transoral robotic surgery between 2008 and 2011.
Other Ohio State researchers involved in this study were Bianca Alvarez, Kiran Kakarala, Kasim Durmus, Ted N. Teknos and Ricardo L. Carrau.
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only seven centers funded by the NCI to conduct both phase I and phase II clinical trials. The NCI recently rated Ohio State’s cancer program as “exceptional,” the highest rating given by NCI survey teams. As the cancer program’s 210-bed adult patient-care component, The James is a “Top Hospital” as named by the Leapfrog Group and one of the top cancer hospitals in the nation as ranked by U.S.News & World Report.
This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
September, 2012|Oral Cancer News|

Perspectives on Coping Among Patients With Head and Neck Cancer Receiving Radiation

Source: MedScape News Today

Abstract and Introduction


Purpose/Objectives: To describe coping among patients with laryngeal and oropharyngeal cancer during definitive radiation with or without chemotherapy.
Research Approach: Qualitative content analysis conducted within a larger study.
Setting: Two radiation oncology outpatient clinics in Baltimore, MD.
Participants: 21 patients with oropharyngeal or laryngeal cancer.
Methodologic Approach: Interviews with open-ended questions were conducted during treatment. Questions covered topics such as coping during treatment, treatment-related issues, and resources.
Main Research Variables: Coping, treatment, and coping resources.
Findings: Patients’ self-assessments suggested they were coping or that coping was rough or upsetting. Issues that required coping varied over four time points. Physical side effects were problematic during and one month after treatment completion. Patients used coping to manage the uncertainties of physical and psychological aspects of their experience. Family and friend support was a common coping strategy used by patients, with the intensity of side effects corresponding with the support provided across time points.
Conclusions: Findings confirm previous research, but also provide new information about ways in which patients with head and neck cancer cope with their illness experience. Emergent themes provide insight into patients’ feelings, issues, and assistance received with coping.
Interpretation: Patients with head and neck cancer need education on the amount and severity of side effects and should be appraised of potential difficulties with scheduling, driving, and other logistic issues. Patients also should be informed of helpful types of support and coping strategies. Additional research is needed to expand the findings related to patients’ coping with treatment and to explore the experiences of family and friends who provide social support.


Head and neck cancer (HNC) accounts for 3% of all cancers in the United States and is twice as common in men compared to women (National Cancer Insitute [NCI], 2011). The incidence in the United States was estimated to be 52,000 new cases in 2011 (NCI, 2011). Treatment for HNC is multimodal, including surgery, radiation, and often chemotherapy. Patients’ illness experiences involve physical symptoms, side effects from treatment, symptom distress, and psychological distress (Archer, Hutchison, & Korszun, 2008; Haman, 2008). Patients also experience uncertainty about the effectiveness of an unfamiliar treatment, their ability to manage daily living, and long-term effects of the disease and treatment (Rose & Yates, 2001). Because of uncertainty, each patient perceives illness, cognitively appraises his or her situation, and copes with illness differently (Mishel, 1988).

Patients with HNC experience an array of physical symptoms resulting from their cancer and its treatment (Chandu, Smith, & Rogers, 2006). Symptoms related to side effects of radiation include dysphagia, xerostomia, pain, fatigue, altered taste, mucositis, skin changes, and weight loss (Olmi et al., 2003; Khoda et al., 2005). Symptoms related to side effects of chemotherapy include difficulty swallowing, anemia, nausea, neutropenia, diarrhea, and mucositis (Lambertz, Robenstein, Mueller-Funaiole, Cummings, & Knapp, 2010; Schrijvers, Van Herpen, & Kerger, 2004). Patients with HNC may experience several of those symptoms and side effects at any time during their treatment.

Symptom distress is defined as the degree or amount of physical or mental upset, anguish, or suffering experienced from specific symptoms (Rhodes & Watson, 1987). Few researchers have examined symptom distress among patients with HNC. Lai et al. (2003) reported that patients undergoing treatment had a moderate amount of symptom distress related to dry mouth, fatigue, loss of appetite, insomnia, and pain. Symptom distress also changes over time in response to the perceived difficulties of patients as a result of the physical and psychological demands of treatment (Haisfield-Wolfe et al., 2011). Symptom distress among patients with HNC can influence coping with symptoms and psychological distress (Elani & Allison, 2010).

Psychological distress, including the presence of anxiety, depression, and depressive symptoms, is present during the course of HNC treatment. Patients experience high levels of anxiety, particularly at diagnosis and pretreatment (Horney et al., 2011). Researchers have found depression and depressive symptoms prior to treatment (Baile, Gibertini, Scott, & Endicott, 1992; Davies, Davies, & Delpo, 1986), during treatment (Haisfield-Wolfe, McGuire, Soeken, Geiger-Brown, &, De Forge, 2009; Kugaya et al., 2000), at the completion of radiation treatment (Katz, Irish, Devins, & Gullane, 2003; Sehlen et al., 2003), and three months after diagnosis (Hammerlid, Silander, Hornestam, & Sullivan, 2001).

Uncertainty in illness is defined as an inability to determine the meaning of events, assign values to objects and events, and accurately predict outcomes (Mishel, 1988). Uncertainty and symptoms have been shown to interfere with adaptation to cancer (Bailey, Mishel, Belyea, Stewart, & Moher, 2004), and high levels of uncertainty interfere with coping (Mishel, 1984). In studies of patients with cancer, increased uncertainty has been related to depression (Bailey et al., 2004), poorer coping with stress (Badger, Braden, & Mishel, 2001), and inadequate psychological adjustment (Christman, 1990). However, few research studies have addressed coping in the context of uncertainty among patients with HNC.

Coping is defined as a “cognitive and behavioral effort to manage specific external or internal demands and conflicts that are appraised as taxing or exceeding the resources of a person” (Lazarus & Folkman, 1984, p. 112). Cognitive appraisal of taxing situations is a prerequisite for initiation of coping attempts that are aimed at adapting to the new reality of living with HNC. Variables associated with adaptation include those of a physical, psychological, and social nature. Research that investigates coping among patients with HNC, focusing on areas patients cope with and what coping strategies they use, is limited. Chaturvedi, Mbulaiteye, and Engels (2008) found that major concerns faced by patients with HNC were worries about their current illness and future (e.g., physical evaluation, communication, inability to perform usual tasks, finances, being upset).

During treatment, patients with HNC cope with symptoms and worries such as weight loss, dry and sore mouth, difficulty masticating and swallowing food, altered perception of taste, and missing meals (Lees, 1999). Patients receiving radiotherapy reported experiencing insufficient information and lack of time to ask questions (Larsson, Hedlin, & Athlin, 2007). Patients also have described coping with “disruption of their daily lives,” “waiting in suspense,” and “being left to their own devices” (Larsson et al., 2007, p. 324). Other areas identified as requiring coping after treatment were feelings of being self-diminished, underreported suffering, and loss of meaning in life (Moore, Chamberlain, & Khuri, 2004). Six to 12 months after treatment, patients were faced with physical changes, concerns about cancer, difficulties with work, interpersonal relationships, and social functioning (Semple, Dunwoody, Kernohan, McCaughan, & Sullivan, 2008).

Coping strategies used by patients with HNC vary. List et al. (2002) found that at pretreatment, patients with HNC primarily used social support. Recently treated patients with HNC used a greater number of coping strategies and commonly employed emotional ventilation, disengagement, denial, and suppression of competing activities (Sherman & Simonton, 2010). Elani and Allison (2010) found an association between levels of patients’ anxiety and depression and the types of coping strategies used. Those with higher levels used more self-blame, wishful thinking, and avoidance strategies. Thambyrajah, Herod, Altman, and Llewellyn (2010) examined benefit finding after HNC treatment and found that major themes were change in life priorities, greater closeness to family and friends, a greater awareness of self, and spirituality. Those few studies demonstrate that although patients with HNC are challenged with numerous physical, psychological, and social effects, their coping remains poorly understood.

Patients cope with symptoms and side effects, worry about disruption in their lives, and often are left to their own devices (Larsson et al., 2007; Lees, 1999). Patients also experience loss of meaning in life, underreport their pain, feel (or are) disfigured, and have changes in interpersonal relationships (Moore et al., 2004). They verbalize that they feel concerned about the uncertainties of cancer recurrence and daily living (Semple et al., 2008). Despite that large burden, few intervention studies have been designed to assist patients with HNC in coping. Learning more about how patients with HNC cope during each phase of their cancer experience will provide clarity in understanding the coping needs of and strategies used by this population.

The purpose of this study was to describe coping in the context of uncertainty among patients with laryngeal and oropharyngeal cancer during definitive radiotherapy with or without chemotherapy over four time points. This work was conducted as a substudy within a larger, longitudinal descriptive study (Haisfield-Wolfe et al., 2009) examining symptoms, symptom distress, depressive symptoms, and uncertainty.

Mishel’s (1988) Uncertainty in Illness Theory (UIT) guided the study research. UIT centers on an ill individual’s appraisal and coping with uncertainty. UIT views coping as a context-specific behavior in which an individual appraises and manages uncertain objects or events as a threat or as a positive challenge (Lazarus, 1967; Lazarus & Launier, 1978; Mishel, 1988). This substudy focuses on coping related to uncertainty. In designing this substudy, the researchers developed three open-ended interview questions to illicit information regarding how patients with HNC cope with treatment. Exploring coping within the context of uncertainty will help increase understanding of coping issues and strategies, with the ultimate aim of developing interventions that will improve practice.


Design, Setting, and Sample

The current study is a descriptive, qualitative content analysis of open-ended questions that patients answered about their coping during treatment. Patients were recruited from radiation oncology clinics at two cancer centers in Baltimore, MD. The sample consisted of 21 patients who met the following inclusion criteria: being aged 18 years or older, newly diagnosed with oropharyngeal or laryngeal cancer, and undergoing definitive radiation with or without chemotherapy. Patients were interviewed at four time points: week 1 (treatment initiation), week 5 (midpoint in treatment), week 9 (end of treatment), and week 12 (one-month visit with radiation oncologist after completion of radiation).

Procedures and Analysis

Approval was obtained from the human subjects institutional review boards at the University of Maryland Medical Center and Johns Hopkins Medical Institutions. Procedures were similar at each site, with physicians and nurses screening new patients for eligibility and identifying those interested in participating. Those individuals then were contacted by the researchers. Of 24 patients meeting inclusion criteria, 21 signed informed consent and provided demographic information. Patients who declined participation stated they were overwhelmed by their diagnosis and schedule. During a structured interview that was conducted as part of the larger study, researchers used the following prompts at each time point.

  • Tell me about how you are coping during treatment.
  • Tell me about any issues related to your treatment.
  • What resources are helping you to cope?

Depending on patients’ responses, the researchers occasionally asked additional questions for clarification. Patients were given as much time as needed to answer the questions, with the average interview lasting 15–30 minutes. Participants’ responses were recorded manually.

The recorded responses were categorized by time point and entered into a Microsoft® Word® document. Using a content analysis approach, the first author examined the text. A qualitative method was used to sort words and sentences having aspects related to each other by content and context into content areas (Graneheim & Lundman, 2004; Krippendorff, 2004). After rereading the whole interview again, content areas were labeled. The individual content areas were tabulated to identify the frequency with which they occurred (Krippendorff, 2004) and then discussed by the researcher and two HNC content area experts. When the researcher or the content experts had different perspectives, discussion occurred until consensus was reached. The categories and their content then were formulated into themes. Finally, the data were reviewed and judged by an HNC survivor who agreed that the themes and content reflected the experience of patients with HNC coping during and after treatment.

Study integrity was established using the aspects of trustworthiness: credibility, dependability, transferability, and confirmability (Lincoln & Guba, 1985). Credibility was demonstrated in the unique responses of patients with HNC to the interview questions, which focused on specific areas of coping with treatment. Dependability was demonstrated not only in the agreement among HNC experts and researchers regarding the results, but also by similar research findings in the literature that are reported in the Discussion section of this article. Transferability was judged by HNC content experts and an HNC survivor who reviewed the findings and agreed that they were transferable to other HNC contexts and settings. Finally, confirmability was maintained when a code book was developed and an audit trail of coding and content area decisions were recorded by the researchers to help ensure rigor and provide guidance for future research.


Demographic and Clinical Characteristics

Sample characteristics are presented in Table 1 . Most patients were Caucasian, married, and men. The mean age was 59.2 years (SD = 9.2), and most patients had 12 years of education. Five patients reported a prior mental health disorder, and one patient was taking antidepressant medications. All patients were receiving radiation treatment at the time of the study, and 15 patients were receiving concomitant chemotherapy.

Open-ended Questions

Coping During Treatment: See Table 2 for the number of participants reporting each theme across time points. Exemplars for the three most prevalent themes that emerged related to coping are presented in Table 3 . At all four time points, the most prevalent theme was the patient’s self-perception of managing to cope. Responses revealed degrees of coping, for example, “quite well,” “as expected,” or “fair.” More than half of the patients reported they were coping with their illness and treatment. Although patients self-perceived they were coping across time points, they also identified physical and psychological issues that challenged their coping abilities. The second most prevalent theme was upsetting or rough experience, which increased over time. At the beginning of treatment, patients reported areas of difficulty with coping as stress related to disease and treatment. At midtreatment, patients reported bothersome side effects. At end of treatment, patients reported coping with aspects of treatment related to managing stressful events or severe side effects. One month after treatment, patients reported being upset about not feeling better by this point in time.

The third most prevalent theme was anticipation, which was highest at baseline and end of treatment (week 9). Patients were anticipating the end of both treatment and side effects. Responses that demonstrated anticipation included “I’m counting the days,” or “I can see the end of the tunnel.” Patients also reported using coping strategies (e.g., blogging, walking, accepting assistance from family or friends, acceptance of their illness, denial).

Issues Related to Treatment: Selected exemplars for the three most prevalent themes related to issues during treatment are presented in Table 4 . The most prevalent theme throughout the four time points was having physical side effects related to treatment, which increased at midtreatment and declined at end of treatment and one month after treatment. Patients reported 16 different side effects: weight loss, taste changes, sore throat, skin sores, pain, nausea, hiccoughs, hearing loss, fatigue, excess mucous, dry throat, difficulty talking, difficulty eating or swallowing, anorexia, and change in body image. One month after completion of treatment, patients still reported persistent symptoms (e.g, pain, difficulty swallowing, fatigue). Of note, the second most prevalent theme (six patients at weeks 5 and 9) was minimal or no issues, with the frequency declining over time. The third most prevalent theme was fear, anxiety, or worrying, which was present at all time points, but was most prevalent at baseline and one month after treatment. Exemplars emphasized the uncertainty associated with completion of treatment, for example, “fear of recurrence of cancer” and “don’t know what to expect.”

Assistance With Coping: Illustrative exemplars for the three most prevalent themes related to assistance are shown in Table 5 . The most prevalent theme was family support, with the majority of patients reporting family as the main source of support received over the four time points. The second most prevalent theme was friend support, which also persisted over four time points. Many patients told stories about how their friends and family had supported them. As the number of side effects increased at midtreatment and end of treatment, the number of individuals supporting the patient increased. At end of treatment (week 9), patients reported the importance of hospital personnel. One month after treatment, the amount of family support decreased and the interactions with friends increased. The third most prevalent theme was mental outlook, which increased over time. Coping strategies reported included Web support, keeping a normal schedule, weekly massage, walking, keeping busy, working at home, journaling, pets, and going to the mall for a few hours to take a “minivacation.”


The results indicate that patients used coping to manage the uncertainties of physical and psychological aspects of their experience. Emergent themes provided insight into patients’ issues and feelings, as well as the support they received during treatment and afterward. Common themes uncovered for each question will be discussed briefly.

Coping at Each Treatment Time Point

Coping is defined as managing internal and external demands of illness (Lazarus & Folkman, 1984). Although the majority of patients perceived that they were coping, they reported different degrees of individual coping (e.g., “excellent,” “fair”) and noted issues that influenced how they coped, such as symptoms, fear, or anxiety. Therefore, most individuals appeared to be coping with the internal and external demands of treatment, with the exception of those who found their situation to be rough or upsetting. Interestingly, patients who reported that their coping was rough or upsetting were not the same grouping of patients across all time points. Patients reported better coping or more difficulty coping depending on the time point; for example, a patient who was coping adequately at baseline and midtreatment reported not coping well at end of treatment because of pain when swallowing. The adequacy of coping appeared to vary depending on the physical and psychological demands the patient had to face. Anticipation emerged at week 9 when patients were experiencing their worst symptoms and were anticipating the end of treatment and the results of their scans, which would determine whether the treatment was successful. That appears to be similar to the theme of waiting in suspense reported by Larsson et al. (2007), who studied patients with HNC six to eight weeks after radiotherapy. Those findings highlight a major issue among patients with HNC: the fear of recurrence experienced by cancer survivors. Coping interventions are needed to assist patients with that issue. One strategy is to educate patients about the wide variety of coping strategies used by participants in this substudy.

Issues Related to Treatment

Physical side effects of treatment were the most prevalent theme identified as an issue to be coped with, revealing specific areas of concern for patients with HNC and verifying findings of other researchers on coping with treatment side effects (Lees, 1999). Specific side effects included difficulty talking, eating, and swallowing; taste changes; excess mucous; and changes in body image. At the midpoint of treatment, patients reported coping with 17 different symptoms, with one patient reporting concurrent presence of three to four side effects at one time. The large number of symptoms patients coped with also has been reported by others (Hansen & Roach, 2007; Vissink, Jansma, Spijkervet, Burlage, & Coppes, 2003). Even one month after treatment, patients still identified pain (mainly in the throat), fatigue, and difficulty swallowing as issues. Treatment-related issues that were problematic for patients generally were related to the processes and procedures of radiation treatment, such as wearing a mask. Both treatment side effects and treatment-related issues revealed the complexities of the illness experience and the challenges posed to patients’ coping. Ten patients reported minimal or no issues at baseline, although that theme was less common at subsequent time points. That finding was surprising because patients were just starting their treatments and one might anticipate that they were coping with a variety of issues. Alternatively, patients simply may have been coping more effectively with their illness. In a study of patients with HNC, Moore et al. (2004) found that patients may underreport their pain and suffering. Finally, the theme of fear, anxiety, or worry was present at all time points, but particularly at baseline and end of treatment. Patients expressed distress about the uncertainties of their illness and their future. They were anxious about treatment and afraid of the outcomes. They worried about the cancer spreading, the treatment schedule, and whether they would endure their treatment. Those fears and worries have been observed by other researchers and clinicians (Hodges & Humphris, 2009). Clearly, uncertainties related to cancer cure and what the future holds are a major issue in the illness experience of patients with HNC. Additional study to determine interventions to assist patients in this area is needed.

Assistance With Coping

Patients used social support to cope with their treatment over the four study time points. They depended on their families and friends to assist them with many aspects of their lives, including traveling to outpatient clinic visits and radiation treatments, daily living activities, communicating with healthcare providers, managing symptoms, scheduling appointments, reading information and educational materials, and engaging in other activities to manage and cope with treatment. Patients also relied on those support people for companionship. As patients progressed with their treatment, more family and friend support was needed to cope with the resulting complexities. Patients used a broad range of coping strategies and also articulated acceptance of their situation or, occasionally, denial.

Of note, some patients took breaks from their situations by going to the mall or turning off their cellular phones to reduce disturbances to their focus on getting well. Sherman and Simonton (2010) reported coping strategies of ventilation, disengagement, and suppression of competing activities, but the wide array of activities reported in the current study provides insights into how patients may take the initiative to cope with their illness and treatment.

Mental outlook was a prevalent theme that helped patients’ cope, and that mindset increased as they progressed through treatment. Patients were convinced that they were getting through the treatment because of their mindset and that they were going to endure. That finding is important because it suggests that patients with a positive mental outlook represent a patient subgroup with a greater ability to cope. Each individual copes with illness and cognitively appraises his or her situation differently (Lazarus & Folkman, 1984). Therefore, mental outlook could have influenced the way patients coped with the physical and psychological demands of illness and treatment.


The current study was limited by the unrecognized individual biases of the researchers and the HNC content experts who analyzed the data. Interviews were conducted at four time points during radiation treatment and, therefore, cannot reflect the entire experience of coping in patients with HNC. During interviews, patients were experiencing fatigue and other factors that may have affected the amount and degree of self-reporting that occurred. Finally, different ways to ask about coping may have revealed different perspectives.

Implications for Nursing

The findings confirm previous research, but also provide new information about the ways in which patients with HNC cope with their illness experience. In the clinical setting, patients with HNC should be educated regarding the number and severity of side effects they may experience and be appraised of potential difficulties with scheduling, driving, and other logistic issues. Patients also should be informed of the types of support and coping strategies that can be helpful. Healthcare providers also should inform patients that they may experience low energy during treatment, thus requiring support of significant others who can assist them with a variety of activities and issues.

Additional research is needed to expand the findings related to patients’ coping during and after treatment because this study was small with limited exploration of coping. For example, future researchers should explore the illness and coping experience of patients with HNC who perceive that they are coping adequately, but then report multiple treatment-related issues. Another area for future research is an exploration of the issues, burdens, and individual coping of family and friends who provide social support to patients with HNC during treatment, which can ultimately strengthen support for patients and reduce the negative impact of caregiving.

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

June, 2012|Oral Cancer News|

Darwin’s Principles Say Cancer Will Always Evolve to Resist Treatment


According to researchers at Moffitt Cancer Center, cancer is subject to the evolutionary processes laid out by Charles Darwin in his concept of natural selection. Natural selection was the process identified by Darwin by which nature selects certain physical attributes, or phenotypes, to pass on to offspring to better “fit” the organism to the environment.

As applied to cancer, natural selection, a key principle of modern biology, suggests that malignancies in distinct “microhabitats” promote the evolution of resistance to therapies. However, these same evolutionary principles of natural selection can be applied to successfully manage cancer, say Moffitt researchers who published an opinion piece in a recent issue of Nature Reviews Cancer.

“Understanding cancer as a disease starts with identifying crucial environmental forces and corresponding adaptive cellular strategies,” said Robert A. Gatenby, M.D., chair of the Department of Diagnostic Imaging. “Cancer is driven by environmental selection forces that interact with individual cellular adaptive strategies.”

Cancer cell development, like any natural selection (or Darwinian) process, is governed by environmental selection forces and cellular adaptive strategies, the authors wrote. Investigating cancer and its proliferation through genetic changes and ignoring the adaptive landscape is most likely futile. Under “selective pressure” of chemotherapy, in this case the “adaptive landscape,” resistant populations of cancer cells invariably evolve.

The authors say that tumors can be thought of as “continents” populated by multiple cellular species that adapt to regional variations in environmental selection forces. Their strategy in offering this metaphor, they wrote, is to “integrate microenvironmental factors at work during cancer’s progression” into the model of the evolution of cancer and, particularly, the evolution of drug resistance.

“Hundreds of mutations can be found in tumors,” said co-author Daniel Verduzco, Ph.D., a post-doctoral fellow at Moffitt. “The physical environment of the early tumor is constantly changing, often in response to inflammation.”

This reality should remind us, they wrote, that natural selection selects for phenotype, for observable physical characteristics, and that natural selection forces at work in local environments causes populations to change phenotypically rather than genotypically.

The authors point out that for most patients with advanced cancers — even when there is a well-known target and a highly specific drug — response to therapy is fleeting owing to the evolution and proliferation of a resistant population of cancer cells.

While targeted therapies have been among the most recent approaches to treating cancer, the authors suggest that the vast changes in the genetics of tumors via mutations reduce the effectiveness of targeted therapies and are a reason why targeted therapies cease to work.

“The emergence of resistance is predictable and inevitable as a fundamental property of carcinogenesis,” Gatenby said. “However, this fundamental fact is commonly ignored in the design of treatment strategies. The emergence of drug resistance is rarely, if ever, dealt with until it occurs.”

In an effort to develop patient-specific, long-term therapeutic strategies, the authors contend that resistance should be anticipated. By “anticipation” in action, they mean developing “adaptive therapies” prior to the emergence of resistance.

Cancer cells, they wrote, can only adapt to immediate selection forces. Cancer cells cannot anticipate future environmental conditions or evolutionary dynamics. This concept, said the authors, may provide an advantage when designing new therapies by “directing” the natural selection processes to prevent the outgrowth of resistant cancer populations and so improve outcomes.

“This potentially unifying theory places the evolution of cancer within a dynamically active landscape,” said Robert J. Gillies, chair of the Department of Cancer Imaging and Metabolism, and program leader of Experimental Therapeutics. “The outcome is cancer’s heterogeneity — those variations that negatively affect targeted therapies to control cancer.

“Recognizing that evolutionary dynamics are an essential component of carcinogenesis itself can lead to development of appropriate therapeutic strategies,” Gillies said. “For example, knowing ahead of time that resistant cancers are likely to emerge provides us with lead time to develop preventive or adaptive therapeutic approaches. We have recently completed studies with our colleagues, Dr. Ariosto Silva , showing that evolutionarily informed therapies can forestall the emergence of resistant tumors for a very long time.”

The authors conclude that we can use our understanding of evolution to strategically direct natural selection toward preventing the outgrowth of resistant cancer populations and, in so doing, improve outcomes.

This research is supported in part by a grant from the McDonnell Foundation (Grant# 220020270) and two grants from the National Cancer Institute, part of the National Institutes of Health (Gant # U54 CA143970 and Grant # R01 CA077575).

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

June, 2012|Oral Cancer News|

2009 Federal Tobacco Tax Increase Cut Number of Youth Smokers by At Least 220,000 in First Two Months Alone, New Study Shows


WASHINGTON, DC – The large federal tobacco tax increase implemented on April 1, 2009, reduced the number of youth smokers by at least 220,000 and the number of youth smokeless tobacco users by at least 135,000 in the first two months alone, according to a new study released today by researchers at the University of Illinois at Chicago.

The researchers emphasized that the study measured only the immediate impact of the tax increase through May 2009, and the number of youth prevented from smoking and using smokeless tobacco would be much larger over time.

The study “showed that a large national tax increase can influence youth tobacco use prevalence within a very short time period,” the researchers wrote. “Adolescents not only respond to tax policy changes, but the speed of their response is fast. The prevalence of smoking and use of smokeless tobacco… dropped immediately following the tax increase in this study, and statistically significant and meaningful changes could be measured and detected within 30 days of the tax increase.”

The study was published online by the National Bureau of Economic Research and can be found at:

The new study comes as the tobacco industry, led by Philip Morris USA and R.J. Reynolds, is spending nearly $40 million to oppose a June 5 ballot initiative in California (Proposition 29) to increase that state’s cigarette tax by $1 per pack. The initiative would reduce smoking and fund research on cancer and other tobacco-related diseases, as well as tobacco prevention programs.

“This study shows exactly why the tobacco industry is spending so much money to oppose California’s Prop 29: They know higher tobacco taxes are very effective at reducing smoking, especially among kids,” said Matthew L. Myers, President of the Campaign for Tobacco-Free Kids. “Because the truth is against them, the tobacco companies are spending huge sums on ads to deceive and confuse voters. Californians should ignore their lies and vote yes on Prop 29.”

Study Findings

A 2009 law approved by Congress, the Children’s Health Insurance Program Reauthorization Act, increased the federal tax rate on cigarettes by 61.66 cents per pack (from 39 cents to $1.0066 per pack) and on moist snuff, the most common form of smokeless tobacco, by 92.5 cents per pound (from 58.5 cents to $1.51 per pound). Taxes were also increased on other forms of smokeless tobacco.

The study investigated the changes in youth smoking and smokeless tobacco use rates following the April 2009 federal tobacco tax increases, using data from the Monitoring the Future survey, an annual national survey of 8th, 10th and 12th grade students. Because the survey is conducted from February through May each year, it coincided with the April 1 tobacco tax increase and provided an effective means to measure the immediate impact.

The study found that the tobacco tax increase had a substantial and immediate impact.

The percentage of students who reported smoking in the past 30 days dropped between 9.7 percent and 13.3 percent immediately following the tax increase, while the percentage who reported using smokeless tobacco dropped between 16 percent and 24 percent (because the survey asked about behavior in the past 30 days, the study used three different models, with different cutoff dates, to fully assess the impact of the tax increase).

Because of the tax increase, there were between 220,000 and 287,000 fewer current smokers and between 135,000 and 203,000 fewer smokeless tobacco users among middle and high school students in May 2009, the study estimated.

The study controlled for other factors that influence youth tobacco use, including individual, family and school characteristics as well as state tobacco control measures, including state cigarette taxes, smoke-free air polices and tobacco control funding.

The study also found that, even as youth tobacco use declined, federal tobacco tax revenues increased by 147 percent in the 12 months following the increase – from $7.1 billion in the 12 months before to $17.5 billion in the 12 months after.

The study “demonstrated that a well-designed, across-the-board tobacco tax policy can delivery both economic and health benefits, and has implications for policymakers at all levels when considering effective tobacco control policies to reduce tobacco use among youth,” the researchers wrote.

Support for the study was provided by the Robert Wood Johnson Foundation and the National Cancer Institute.

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

May, 2012|Oral Cancer News|

Prognostic Significance of HPV Status in Oropharyngeal Cancer

OncologySTAT Editorial Team

Dr. Maura Gillison is Professor of Medicine, Epidemiology, and Otolaryngology at Ohio State University in Columbus.

OncologySTAT: The results of the Radiation Therapy Oncology Group (RTOG) 0129 trial showed that the human papillomavirus (HPV) is an independent prognostic factor in oropharyngeal cancer. Could you tell us about the rationale for this study?

Dr. Gillison: Over the last 10 years, our research has shown that cancers of the oropharynx are actually 2 completely different diseases that can look quite similar. One subset is caused HPV infection, and the other is more closely associated with long-term use of alcohol and tobacco.

Initial studies suggested that the presence of HPV in a patient’s tumor had prognostic significance, but study limitations made that conclusion dubious. We set out to determine whether or not HPV was indeed an independent prognostic factor in head and neck cancer. To show whether there was a direct relationship between HPV infection and head and neck cancer, we needed to prospectively study a uniformly treated and uniformly staged patient population. Thus, we used the study population from the trial conducted by the RTOG. We divided the patients into 2 groups—those whose tumors were caused by HPV and those whose tumors were not—and we compared survival outcomes for the 2 groups.

The results showed that HPV status was the single most important predictor of patient outcome, even more so than disease stage and other well-known prognostic factors such as performance status and presence of anemia. In fact, after accounting for 6 other nonprognostic factors, patients with HPV-positive cancer had less than half the risk of dying from their cancer as did patients whose cancer was HPV negative. At 5 years, that translated into a 30% absolute difference in survival.

On the basis of these results, we can state definitively that HPV is a strong and independent prognostic factor for oropharynx cancers. Currently, tumor HPV status is determined for all patients with head and neck cancer prior to enrollment into a clinical trial. I believe that HPV-positive oropharynx cancer is a completely different disease from traditional head and neck cancer, to the extent that we need to design separate clinical trials that are specific for the HPV-positive patient, as distinct from the HPV-negative patients.

Unfortunately, we have not made true progress over the last 15 to 20 years in therapy for patients with head and neck cancer. The major advances have been in our understanding of the underlying etiology of the disease and its inherent biologic responsiveness. Patients with HPV-negative head and neck cancer, in particular, are still doing extraordinarily poorly. Even with the use of intense, concurrent chemoradiation, as was done in the RTOG trial, 5-year survival is only about 30%.

OncologySTAT: Now that we can stratify patients by HPV status, it will be possible to separate out people who have head and neck cancer related to tobacco use and conduct separate trials on those patients, or investigate different therapies for them.

Dr. Gillison: Exactly. Our data indicate that patients with HPV-positive tumors do extraordinarily well. Some still do die of their cancer, but about 80% are alive and doing well 5 years later. Many of these patients are quite young; it’s not unusual to see patients in their 30s or 40s. If they’re expected to survive their cancer, then they will have to deal with the consequences of the therapy for 30, 40, or 50 years.

OncologySTAT: Are they surviving longer?

Dr. Gillison: They are surviving longer. Now we need to focus on improving their outcomes. The more aggressive approaches being used in head and neck cancer, such as combination therapy with multiple agents, together with standard chemotherapy, biologics, and radiation therapy, all should be studied in HPV-negative patients. The increased toxicity of combined therapies may be warranted in terms of the risk-benefit analysis because these patients have such poor survival. At present, it would be inappropriate to use such therapies for the HPV-positive group.

OncologySTAT: Will you be following the HPV-positive patients over the long term? Patients with head and neck cancer are at risk for second cancers later on.

Dr. Gillison: We analyzed second cancers in our trial and found that they were significantly less likely to occur in HPV-positive patients than in HPV-negative patients. The difference was largely explained by a difference in rates of smoking in the 2 groups of patients. The rate of second cancers is approximately 20% among HPV-negative patients, whereas it’s about 5% in the HPV-positive group.

OncologySTAT: Are there any follow-up studies planned or underway right now?

Dr. Gillison: The National Cancer Institute (NCI) steering committee has adopted my recommendation to design separate clinical trials for HPV-positive and HPV-negative patients. We also hope to conduct clinical trials with the European Organisation for Research and Treatment of Cancer (EORTC) and the French Head and Neck Oncology and Radiotherapy Group. This work will focus on how best to treat patients with HPV-positive head and neck cancer. We don’t know the best treatment strategy, because HPV-positive cancer wasn’t recognized until recently as a unique disease entity.

In the United States, incidence rates of HPV-positive cancer are rising dramatically. NCI data for 2000 put the incidence at 10% per year, but this rate is expected to double in the current decade. Thus, in the future, the alcohol- and tobacco-related cancers are going to be the rare cancers.

We need to figure out as rapidly as possible the standard of care for this cancer. Together with RTOG and the Eastern Cooperative Oncology Group (ECOG), we are in the process of designing a large, randomized phase II study specific to HPV-positive patients. We estimate enrolling 800 to 1,000 patients. Endpoints will include quality of life and toxicity outcomes. Because HPV-positive patients respond so well to therapy, the question now is whether we can reduce the use of intense therapy and thereby decrease the long-term consequences of the therapy. Some therapies used during the last 15 years for head and neck cancer have yielded only a 5% to 8% absolute benefit in 5-year survival, but they have contributed to a 500% increase in morbidity over the long term. Many patients end up not being able to swallow food and are therefore dependent on gastrostomy tubes, which has significant social and quality-of-life implications.

So the goal of that trial is to compare standard-of-care therapy, as it was developed in RTOG 0129, with 2 other treatment algorithms involving reduced-intensity therapy. Hopefully, we will find that reduced-intensity therapy does not compromise survival. We hope we can get answers sooner rather than later.

OncologySTAT: Do you think vaccination is going to have a role in reducing the incidence of HPV-related head and neck cancers over time?

Dr. Gillison: I certainly hope so. Half of my research program involves work on oral HPV infection, looking at its prevalence in the US population, predictors, and the natural history. Soon we will be starting a clinical trial that evaluates whether the currently approved HPV vaccines can more effectively prevent oral HPV infections. We hope to have answers in 5 years.

HPV vaccines are extraordinarily effective (nearly 100%) in preventing cervical dysplasia and cancer among women. Both the Food and Drug Administration and the Centers for Disease Control and Prevention report virtually no evidence of any severe toxicities or negative outcomes from the vaccine. However, only 1 out of 4 parents in the United States have made the decision to have their daughters vaccinated.

OncologySTAT: Pediatricians appear to be proponents of vaccination against HPV.

Dr. Gillison: Yes. I understand that there are social implications to the vaccine, as well as cost-benefit considerations, because the vaccine is expensive. However, my patients look at it this way: If they had the option, in retrospect, of getting 3 vaccines in their teens instead of having to deal with the consequences of a cancer diagnosis for themselves and their families later on, they say it would have been an easy decision.

For HPV-related cancers, we’ve found the Achilles heel, in that HPV is necessary for these cancers, causing about 20,000 cases in the United States every year. The vaccine appears to be fairly effective at every site where it’s been tested. My concern is that, if we can’t make the appropriate decisions on a policy level that could eliminate a cancer for which we’ve identified a single cause, what will we do for all these other cancers, the genetics of which are much more complex? Cancers such as colon cancer and breast cancer are tremendously heterogeneous in terms of genetic predisposition. There’s probably not going to be an Achilles heel for those cancers. In my opinion, potentially 20,000 US families are affected each year by a cancer for which the HPV vaccine holds promise. Worldwide, that’s more than a million cases.

OncologySTAT: What are the implications of your results for community-based oncologists?

Dr. Gillison: The patient population that gets HPV-related head and neck cancer is highly educated; they tend to be of high socioeconomic status. This is a different population than head and neck cancer patients in the past, who, because of their protracted alcohol and tobacco abuse, maybe didn’t advance as well in society as these patients, who tend not to smoke and drink. Patients we see tend to be Internet savvy, and when they read about the profound prognostic significance of the HPV test, they demand it.

If you knew that you had been diagnosed with a cancer for which there was a test that could determine whether you had an 85% chance of 5-year survival as opposed to a 30% chance, you’d probably demand it, too, because you’d want to make plans for your life. Community oncologists should be aware of these data, because any patient with an oropharynx cancer who does not have traditional risk factors probably has an HPV-related cancer.

Unfortunately, a lot of medical oncologists in the community are still unaware of the relationship between HPV and oropharynx cancer. They need to be made aware of the relationship so that they can counsel their patients appropriately. Many patients are completely stumped as to why they’ve gotten this cancer. Community oncologists need to know that HPV testing is available in at least 2 institutions, Johns Hopkins and Ohio State University.

All clinical trials conducted by ECOG and RTOG will now require determination of HPV status for eligibility. Oncologists in the community who refer patients for clinical trials need to be aware of this and know how to counsel their patients when the results come back. There is still a social stigma to having a cancer caused by a sexually transmitted infection, and community oncologists need to be sensitive to that. In my clinical practice, I’ve seen marriages dissolve over the blame game, and relationships strained because of guilt feelings in one partner or the other. Community oncologists need to educate themselves about HPV so that they can handle this difficult counseling.

OncologySTAT: That’s an interesting aspect that we don’t often think about in terms of participation in a clinical trial.

Dr. Gillison: Telling someone that they have a cancer caused by a sexually transmitted infection can have social implications. In my opinion, there should be no stigma associated with it. As an HPV biologist, I recognize that 80% of individuals will have an HPV infection at some point in their life. That may even be an underestimation, as it is based solely on data for cervical cancer. Anal HPV infection and oral HPV infection didn’t factor into those previous estimates.

I see HPV infection as a consequence of being human. Nearly all people who get an HPV infection can handle it immunologically, without developing any health consequences. We don’t know what’s different about the 0.01% of people who develop cancer from the virus and those who don’t. I try to educate people about the high prevalence of HPV infection. Education can help remove the social stigma.

A lot of my patients feel relieved when I tell them how common the infection is. There’s also a perception that HPV infection is an indication of promiscuity, which is not correct. A study done at the University of Washington followed college-aged women from their freshman year forward to assess the incidence of HPV infection. The analysis was restricted to women who were virgins at entry into the study. The women were followed only through their first sexual partner, after which they were censored. By the end of 1 year, 25% of the women had contracted an HPV infection. By the end of 2 years, the incidence had risen to one-third. Men are remarkable reservoirs for HPV infection. An estimated 63% of men in the United States have a genital HPV infection.

So it’s best to think of HPV infection as a consequence of being human and having evolved with the virus for a long time. With this viewpoint, people won’t attach such a stigma to it.

OncologySTAT: It will also be important to determine which patients can have good outcomes despite receiving less aggressive therapy. This could spare them some of the speech and eating problems that result from head and neck cancer.

Dr. Gillison: As the principal investigator on the planned RTOG study, I know some of the comparisons we will be looking at. Less intensive radiation is one option for less aggressive therapy. Most of the complications from therapy are related to patients’ receiving chemotherapy and radiation at the same time; an alternative approach might be to administer these treatments sequentially. Or, if given together, they could be given at lower doses. These are some of the different options being considered for this study.

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

April, 2012|Oral Cancer News|

HPV Vaccine Recommendation for Boys Viewed as Necessary


 As the incidence of head and neck cancers linked to the human papillomavirus (HPV) continues to rise, a federal advisory panel has recommended that all 11- and 12-year-old boys be vaccinated against the virus, igniting further controversy in an area where acceptance of a public health policy has been slow.

The recommendation from the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC) would expand the use of the vaccine beyond the original target population of 11- and 12-year-old girls for whom it is recommended as protection against cervical cancer.

Ezra E. W. Cohen, MD, firmly supports the latest recommendation. “It’s the right move by the CDC,” he said in an interview. “I think it’s a long time coming.”

Cohen said that the fact that the original recommendations targeted cervical cancer created a cultural perception that the vaccine was only intended for girls.

Yet the HPV virus affects men as well. According to the CDC, HPV is associated with about 18,000 cancers in women and 7000 cancers in men each year.

Overall, the incidence of HPV-positive oropharynx cancers increased by 225% between 1988 and 2004, according to National Cancer Institute research. There were an estimated 6700 cases of HPV-positive oropharynx cancers in 2010, up from 4000 to 4500 in 2004.


Cohen said he believes such numbers are going to continue to rise. Even by taking proactive steps in 2011, the vaccine is only intended for children and young adults. HPV that is already circulating will continue to be spread and lead to the development of cancer in certain people who contract it.

“Even if vaccinations were made mandatory, we will not see the effects on cancer for decades,” Cohen said. “Just simply recommending it is probably not going to be enough.”

Indeed, the CDC has found that public acceptance of the HPV vaccine for girls has lagged behind adoption rates for other vaccines. The recommendation has been controversial because HPV is spread through sexual activity, leading many parents to protest over the notion that their children could be engaging in sexual activities at a young age.

Key HPV Vaccination Statistics

  • Coverage for 1 dose of HPV vaccine for girls increased by only 4.4 percentage points to 48.7% in 2010 versus 44.3% in 2009.
  • For girls who received the recommended 3 doses of HPV vaccine, coverage increased 5 points to just 32% in 2010 versus 26.7% in 2009.
  • Of the girls who began the HPV vaccine series, 30% did not receive all 3 doses.
  • Completion of the 3-dose HPV series was lower among blacks and Hispanics than whites.
  • Coverage for 3 doses of HPV vaccine was lower for those living below poverty levels.
  • Poor and minority teens are less likely to receive all 3 recommended doses of the HPV vaccine.

Source: Centers for Disease Control and Prevention. Teen vaccination coverage. 2010 National Immunization Survey (NIS)—Teen. Published August 25, 2011. Accessed November 7, 2011.

The HPV vaccine was first recommended for 11- to 12-year-old girls as well as for teenage girls and women through age 26 in 2006, yet less than one-third of those who started the vaccine series received all 3 doses (Key Statistics, Left).

The FDA has approved 2 products, the quadrivalent Gardasil (Merck) and the bivalent Cervarix (GlaxoSmithKline), as vaccinations against HPV. For girls and young women, both vaccines are recommended as protection against cervical cancer, while Gardasil also protects against anal, vaginal, and vulvar cancers.

The only HPV vaccine recommended for males is Gardasil, a CDC official said in discussing the new recommendations in October.

In a study published in The New England Journal of Medicine in October, a phase III trial demonstrated that Gardasil was 77.5% effective in reducing the rates of anal intraepithelial neoplasia associated with 4 HPV types among 602 healthy men ages 16 to 26 years who have sex with men.

Despite the vaccine’s ability to protect patients from HPV, the vaccine does not protect against a wide variety of other sexually transmitted diseases, including the human immunodeficiency virus.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
April, 2012|Oral Cancer News|