human papillomavirus

Imaging, physical examination find most recurrences of HPV-positive oropharyngeal cancer

Source: www.oncologynurseadvisor.com
Author: Kathy Boltz, PhD

Posttreatment imaging at 3 months and physical examinations during the 6 months following treatment can detect most recurrences in patients treated with definitive radiation therapy for oropharyngeal cancer caused by human papillomavirus (HPV).1 This research was presented at the 2016 Multidisciplinary Head and Neck Cancer Symposium.

A dramatic increase in oropharyngeal squamous cell carcinoma (OPSCC) cases associated with HPV has been reported by the American Cancer Society. Survival rates after definitive radiation therapy have also increased. This has led to the need to determine general time to recurrence and the most effective modes of recurrence detection, to guide standards for optimal follow-up care by oncology teams.

This study examined 246 cases of HPV-positive or p16-positive non-metastatic OPSCC treated with definitive radiation therapy at a single, large-volume cancer center between 2006 and 2014.

Follow-up care included a PET/CT scan 3 months after completing treatment and physical examinations every 3 months in the first year following treatment, every 4 months in the second year and every 6 months in years 3 through 5. Median follow-up care length for all patients was 36 months. Patient outcomes, including recurrence and survival rates, were calculated using the Kaplan-Meier method from the end of radiation therapy.

Most recurrences were detected either by persistent disease appearing on 3-month post-treatment imaging or by patients presenting with symptoms at follow-up examinations.

Disease characteristics that increase the likelihood of recurrence include presenting with 5 or more nodes or having level 4 lymph nodes (P < .05). Distant metastases were a greater risk in patients with a lymph node larger than 6 cm or with bilateral lymphadenopathy (P < .05). “For most patients with HPV-associated oropharynx cancer, after a negative 3-month PET scan, physical exams with history and direct visualization are sufficient to find recurrences,” said Jessica M. Frakes, MD, an assistant member of the department of radiation oncology at the H. Lee Moffitt Cancer Center in Tampa, Florida, and lead author in the study. “Minimizing the number of unnecessary tests may alleviate the financial and emotional burden on these patients, including overall health care costs, time spent away from work and family, and the anxiety of waiting for scan results.” This study also supports the effectiveness of specialist teams in treating HPV-positive OPSCC with definitive radiotherapy (RT). Within 3 years, local control was achieved in 97.8% of all patients in the study; regional control in 95.3%; locoregional control in 94%; and freedom from distant metastases in 91.4%. The 3-year overall survival rate was 91%. “We were pleasantly surprised by the high cure rates and the low permanent side effect rates for these patients,” said Frakes. “These findings demonstrate that individuals with HPV-associated oropharyngeal cancer who are treated with definitive RT and cared for by multidisciplinary specialists have excellent outcomes.” Reference: 1. Frakes JM, Naghavi AO, Strom T, et al. Detection of recurrence in HPV associated oropharynx squamous cell carcinoma. Presented at 2016 Multidisciplinary Head and Neck Cancer Symposium; Scottsdale, AZ; February 18, 2016. Abstract 6.

March, 2016|Oral Cancer News|

NCCN Is ‘Vague,’ So Study Clarifies H&N Cancer Follow-up

Source: www.medscape.com
Author: Nick Mulcahy
 

Clinical guidelines can sometimes be slow to respond to epidemiology.

Take the case of oropharyngeal cancers that are associated with human papillomavirus (HPV) infection. They are increasingly common in the United States and, as several studies have demonstrated, have better survival than cancers of this type that are not HPV-positive.

Nonetheless, one of the beacons in oncology care, the National Comprehensive Cancer Network (NCCN), recommends the same follow-up care guidance for oropharynx squamous cell carcinoma whether it is associated with HPV or not, according to two experts.

For post-treatment follow-up, including recurrence detection, “the NCCN guidelines are one-size-fits-all,” said Jessica Frakes, MD, a radiation oncologist at the Moffitt Cancer Center and Research Institute in Tampa, Florida.

She spoke during a press briefing at the Multidisciplinary Head and Neck Cancer Symposium 2016 in Scottsdale, Arizona.

“You are exactly right: the NCCN is fairly vague about when to perform imaging,” said Christine Gourin, MD, an otolaryngologist at Johns Hopkins University in Baltimore, who moderated the press briefing.

Dr Frakes and her colleagues have stepped into this informational breach with a new study that might help clinicians gain clarity on the use of surveillance imaging in HPV-positive oropharyngeal cancer and reduce its frequency.

“The purpose of our study is to determine when these patients fail and when they have side effects so we know how to guide optimal follow-up,” Dr Frakes explained.

The study authors examined 246 cases of nonmetastatic HPV-positive oropharynx squamous cell carcinoma treated with radiation therapy at Moffitt from 2006 to 2014. Most patients (84.6%) received radiation therapy and a concurrent systemic therapy; a minority (15.4%) received radiation alone. Most patients had locally advanced disease.

The team’s major finding was that the great majority of recurrences and toxicities can be detected with imaging 3 months after treatment with definitive radiation therapy and physical exams during the 6 months after treatment.

Specifically, all six local failures were detected by sight or with flexible laryngoscopy conducted during physical exams in that 6-month period.

Eight of the nine regional recurrences (89%), 12 of the 13 locoregional failures (92%), and 15 of the 21 distant recurrences (71%) were detected from symptoms or with a PET/CT scan 3 months after treatment

“For most patients with HPV-associated oropharynx cancer, after a negative 3-month PET scan, physical exams with history and direct visualization are sufficient to find recurrences,” said Dr Frakes in a press statement.

The findings — and the suggestion that PET scans can be suspended after 3 months — are akin to what happens in clinical practice at Johns Hopkins, Dr Gourin reported.

“We have stopped routinely imaging patients after 3 months if a PET is negative, and it’s true that we do pick up more recurrences clinically than radiologically,” she said.

Cutting down on PET scans in this patient population is a good thing, suggested Dr Gourin. “I think we probably do too much post-treatment surveillance imaging,” she said.

There are multiple benefits to suspending imaging, including potentially lowering patient stress because they know their recurrence risk is low and don’t have anxiety related to test results.

Plus, there is a cost reduction.

“A PET scan costs $1500 [for the patient],” said Dr Frakes. Dr Gourin noted that the test is even more expensive in her geographic region.

Factors That Increase Recurrence Risk

The study authors also identified disease characteristics that increase the likelihood of recurrence.

Both regional and distant failures were more common in patients who presented with five or more positive lymph nodes or who had level IV lymph nodes (P < .05).

And the risk of developing distant metastases was greater in patients with a lymph node larger than 6 cm or with bilateral lymphadenopathy (P < .05).

But overall, the results are “excellent,” said Dr Frakes. Within 3 years, the rate of local control was 97.8%, of regional control was 95.3%, of locoregional control was 94.0%, and of freedom from distant metastases was 91.4%. The rate of 3-year overall survival was 91.0%.

Toxicities were also low, which is an endorsement of the multidisciplinary care, said Dr Frakes.

Only 9% of patients experienced severe late toxicities, including 19 grade 3 toxicities and two grade 4 toxicities. These were resolved in 16 of 21 toxicities (76%) at the time of last follow-up.

Most of the toxicities and/or recurrences (64%) occurred in the first 6 months after treatment; only four events occurred more than 2 years after treatment.

Dr Gourin questioned the low rate of serious late toxicities seen with this nonsurgical management of patients. Such a low rate “has not been our experience” at Johns Hopkins, she said.

Dr Frakes and Dr Gourin have disclosed no relevant financial relationships.

Multidisciplinary Head and Neck Cancer Symposium (MHNCS) 2016: Abstract 6. Presented February 19, 2016.

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

February, 2016|Oral Cancer News|

Oral cancer less likely in women who have more sex; but not the same for men

Source: www.parentherald.com
Author: Diane Ting

Having more sex partners reduces the chance of oral cancer for women. Unfortunately, men are more likely to become infected as the number of oral sex partners increases.

A study suggests that women who have more vaginal sex partners appear to have a lower risk of oral human papillomavirus (HPV) infections. The information was released during the annual conference of the American Association for the Advancement of Science. Throat and mouth cancer are linked to HPV, which is one of the most prevalent sexually transmitted diseases. HPV is rather common, as most people are treated of the virus within two years.

According to the study published by the Journal of the American Medical Association (JAMA), oral sex may increase the risk of head and neck cancer by 22 percent. In the last 20 years, the number of oral cancer patients has risen to 225 percent.

Oral cancer is typically linked to lifestyle causes such as heavy drinking and smoking, according to Mirror. Two in three sufferers of oral cancer were men, which made experts question the imbalance.

HPV is the same cancer that causes cervical cancer in women. Research states that because women are first exposed to HPV vaginally, they may develop an immune response that prevents them from getting the infection.

Unfortunately, research suggests that this may not be the same for men as they are found twice more likely to develop oral cancer. As the number of oral sex partners increase, the risk of oral HPV infections also increases. It is believed that oral sex may be the main cause at which the HPV ends up in the mouth. “Our research shows that once you become infected, men are less likely to clear this infection than women, further contributing for the cancer risk,” according to Gypsyamber D’Souza, a professor at Johns Hopkins University in Baltimore.

Oral sex can dramatically increase a person’s risk of the common human papillomavirus (HPV) by 22 times, which can eventually lead to cancer, according to a study. While HPV is very common and easily treatable, HPV may not go away in some cases particularly with men. In some rare instances, the virus can lead to cellular changes in the mouth and throat, which can lead to cancer.

Middle-aged white men are particularly at high risk compared to other races, according to Daily Mail. The US Centers for Diseases Control and Prevention (CDC) has highly recommended all pre-teenagers to take the HPV vaccination before they become sexually active.

February, 2016|Oral Cancer News|

HPV vaccination rates are low, especially in Kansas and Missouri, and cancer experts are alarmed

Source: www.kansascity.com
Author: Lisa Gutierrez
HPV (2)The HPV vaccine is recommended for girls and boys starting at ages 11 to 12. But in state-by-state comparisons, children in Kansas and Missouri rank at or near the bottom of the list. John Amis The Associated Press

 

The University of Kansas Cancer Center recently joined nearly 70 other cancer centers across the country to sound an alarm about the HPV vaccine.

Many children still are not getting the recommended vaccine for human papillomavirus, which causes head and neck cancer in men and women, cervical cancer in women and a host of other cancers in both.

In Kansas and Missouri, less than 49 percent of girls have received the vaccine, according to the Centers for Disease Control and Prevention. Kansas ranks dead last in the nation, and Missouri is near the bottom. Both states rank low for the number of boys who are vaccinated too.

The public call from KU’s cancer center was blunt: The vaccine prevents cancer. What’s the problem?

“It absolutely breaks my heart,” said Terry Tsue, physician-in-chief at the University of Kansas Cancer Center. “We have two vaccines against cancers that are caused by virus, the hepatitis A vaccine and the HPV vaccine. Otherwise, we don’t have a vaccine that prevents cancer.

“There are thousands and thousands of people dying annually from this disease that could have been prevented had we had this vaccine 30 years ago. We didn’t have it and were so slow in adopting it that for the next 30 years we’re going to lose the same number of people, and more, because it’s spreading.”

The nation’s cancer centers banding together to issue a collective statement was a rare move for those involved in cancer research and prevention.

The low HPV vaccination numbers represent a public health threat, said cancer center officials, who asked health care providers and parents to take advantage of the vaccine.

Considering President Barack Obama’s new “moonshot” efforts to cure cancer, “this is one example of actions that can be taken today to make a very big difference in the future cancer burden,” said a statement from Ernest Hawk, vice president and division head of cancer prevention and population sciences at the University of Texas MD Anderson Cancer Center.

Tsue is stunned by what people don’t know about HPV. For instance, about 70 percent of parents apparently don’t know that the vaccine is recommended for boys as well as girls.

The vaccine not only prevents “female” cancers — cervical, vaginal, vulvar — but it also prevents cancer in the throat, known as oropharyngeal cancers. And three times as many men as women get throat cancer from HPV, says Tsue.

Twenty percent of patients with HPV-related throat cancers die within five years.

“Our practitioners aren’t aware of the magnitude and this kind of tsunami of cases,” said Tsue, a head and neck surgeon. “Throat cancer related to HPV is growing up to 5 percent a year. No other cancer is growing like that. And it will surpass cervical cancer caused by HPV by 2020.”

According to the CDC, HPV infections are responsible for about 27,000 new cancer diagnoses each year in the U.S.

So the CDC recommends that all boys and girls get a three-dose round of HPV vaccine shots at the ages of 11 or 12. The vaccine can be up to 93 percent effective when it’s given at that optimal time, CDC officials say.

But vaccination rates are low. The U.S. Department of Health and Human Services set a goal to have 80 percent of American girls ages 13 to 15 fully vaccinated by the year 2020. But four out of 10 girls remain unvaccinated, according to CDC statistics, and fewer than six out of 10 boys have been vaccinated.

Tsue says that health professionals are battling a lot of misinformation and misconception among the public. Surveys of parents, for instance, show that many mistakenly think HPV has something to do with HIV.

Tsue thinks another issue is that parents equate the vaccine with sex because the virus is most commonly sexually transmitted, though it can sometimes be transmitted without sexual contact.

Parents tells survey takers that their children don’t need the vaccine because their kids aren’t having sex.

However, most men and women in the United States will be infected with at least one type of HPV at some time in their lives.

“Eighty percent of adults get HPV in their lives — 80,” said Tsue. “So this isn’t for the hooker on the corner of the red light district. This is 80 percent of the U.S. population will have HPV sometime in their life.”

Tsue thinks that some parents also believe that having their children vaccinated will somehow give them free rein to have sex or will promote promiscuity, though studies have shown that getting the vaccine doesn’t make kids more likely to have sex at a younger age.

“So your 10-year-old who has no idea what the shot they’re getting is will subsequently go out and have sex the next week because they got a shot that prevents the HPV virus?” said Tsue. “That’s (what) we’re dealing with.”

Though the vaccine is not known to cause serious or long-term side effects, questions about its safety linger for some parents, particularly those who have sworn off childhood vaccines. Five years ago, then-congresswoman Michele Bachmann of Minnesota charged during a presidential debate that the vaccine was “very dangerous” and caused “mental retardation.”

A study published in Pediatrics in 2013 showed that among the most frequent reasons parents gave for not having their children vaccinated was fear of the vaccine’s safety.

The website VacTruth.com — run by a father who says his son was harmed by childhood vaccinations — published a story last month charging that reports of serious side effects and deaths linked to HPV vaccines are being kept secret from the public.

Thousands of young girls, the story claims, “have fallen seriously ill, have had their health completely ruined after these vaccines and many have died.”

It cited records from the website Judicial Watch, which describes itself as “a conservative, nonpartisan educational foundation,” claiming that one of the HPV vaccines, Gardasil, is linked to “thousands of serious adverse reactions and debilitating side effects, including seizures, blindness, paralysis and dozens of deaths.”

Judicial Watch, which has been investigating the vaccine for the last few years, has dubbed the HPV vaccine “a large-scale public health experiment.”

The medical community considers the vaccine one of the safest around.

“All this bad press about vaccines, how it kills people, how it causes autism, all false,” said Tsue.

Tsue talks to small groups of health care professionals about HPV-related cancers on his quest to promote the vaccine. He believes that more pediatricians and family practitioners should start talking to parents about it too.

“We need to help providers to make a strong cancer prevention recommendation for vaccinating 11- and 12-year-old boys and girls with the HPV vaccine,” Anna Giuliano, director of the Center for Infection Research in Cancer at Moffitt Cancer Center in Tampa, Fla., told NPR earlier this month.

“If all the pediatricians and family practice doctors were making that strong recommendation, I think we would see a strong increase in the rate of uptake in that vaccine.”

Tsue and other cancer experts would like to see the HPV vaccine added to the lineup of regularly scheduled vaccines schoolchildren already receive: tetanus, diphtheria, whooping cough and meningitis, among them.

Tsue supports mandatory vaccination too — neither Kansas nor Missouri mandates the vaccine — but that’s been a hard sell already.

In 2011, Gov. Rick Perry of Texas had to reverse his decision to make the vaccine mandatory when conservative parents in his state revolted.

The Rhode Island General Assembly faced the same objections last year after it required the vaccine for all seventh-graders. The Rhode Island Center for Freedom & Prosperity held a rally protesting the mandate on the vaccine with parents who said their children got sick from it.

Parents also argue that they should be allowed to make the vaccination decision themselves, a point that the American Civil Liberties Union supports Rhode Island parents on.

Meanwhile, public health officials in Massachusetts itching to do something to raise the rate of HPV vaccinations there are watching Rhode Island’s success with the mandate, according to The Boston Globe.

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

February, 2016|Oral Cancer News|

New research opens door to understanding human tonsil cancer



Source: medicalxpress.com
Author: staff

Researchers at Simon Fraser University and the BC Cancer Agency have developed a groundbreaking method to identify and separate stem cells that reside in the tonsils. Their research, which sheds new light on the fight against oral cancer, is published today in the journal Stem Cell Reports.

While stem cells in many other body tissues have been well studied, little is known about these stem cells, says researcher Catherine Kang, a PhD student in the Department of Biomedical Physiology and Kinesiology and lead author of the paper. Ninety per cent of human tonsil cancers show evidence of HPV (human papillomavirus) infection. But little is known about its role in causing these cancers. Researchers suspect it is a key player, as HPV is the major risk factor for cervical cancer.

Kang, who is working with BPK professor Miriam Rosin, director of the BC Oral Cancer Prevention Program, and UBC professor Connie Eaves of the Terry Fox Laboratory, was interested in finding out why the tonsil is particularly susceptible to HPV and wondered if it might have something to do with the stem cells of the tissue that coats the tonsils.

When she purified these cells and made them incorporate a cancer-causing gene normally transmitted by HPV, the cells grew abnormally in a special tissue culture system, and created what one might imagine what the beginning stages of human tonsil cancer would look like.

“This is a very exciting finding, as it is the first stage of human cancer development that researchers need to learn how to detect and eliminate,” says Kang. The study shows how it can now be done and then studied at will in a petri dish using cells isolated directly from human tonsils.

Cancer of oropharynx, or the tonsils in particular, is an important health concern with rising incidence worldwide, especially in men. The researchers, including Dr. Raj Kannan of the BC Cancer Agency’s Terry Fox Laboratory, say this new method will now allow these next steps to go forward not just here, but around the world, to stop this global trend in its tracks.

November, 2015|Oral Cancer News|

Less Is More for HPV Oropharyngeal Cancer Reduced-intensity regimen clears disease in 86% of cases

Source: www.medpagetoday.com
Author: Charles Bankhead
 

SAN ANTONIO — Less intense treatment of low-risk human papillomavirus (HPV)-related oropharyngeal cancer achieved a high rate of pathologic complete response (pCR) and favorable patient-reported outcomes, a preliminary trial showed.

Overall, 37 of 43 (86%) patients achieved pCR with deintensified chemoradiation, including all but one evaluable primary tumor. The pCR rate was virtually identical to historical rates achieved with standard regimens, according to Bhishamjit Chera, MD, of the University of North Carolina (UNC) at Chapel Hill, and colleagues.

Selected patient-reported adverse events peaked during the first 6 to 8 weeks and then declined thereafter. About 40% of patients required feeding tubes for a median duration of 15 weeks, but no patients required permanent feeding tubes, they reported here at the American Society for Radiation Oncology meeting.

The regimen consists of lower doses of radiotherapy and concurrent cisplatin, administered over 6 weeks. With high-dose therapy, the radiation protocol requires an additional week.

“Though we have limited follow-up, the pathological complete response rate with this reduced-intensity chemoradiotherapy regimen is very high in patients with favorable-risk oropharyngeal squamous-cell carcinoma,” Chera said. “The early quality-of-life measurements are encouraging, particularly the data on swallowing. We are optimistic that these results with reduced-intensity treatment will translate into good long-term disease control with less toxicity.”

The study reflects the current trend and momentum in the management of HPV-positive oropharyngeal cancer, said Zain Husain, MD, of Yale Cancer Center in New Haven, Conn.

“This is the second study to show that de-escalation of therapy might work, and so far, the results really look good,” Husain told MedPage Today. “This is a really important issue, and all of our trials are moving in that direction.”

NRG Oncology (formerly RTOG) has already launched a trial using the UNC regimen, “which gives us a lot of confidence that this is a good regimen,” Husain added. Nonetheless, reduced-intensity treatment remains investigational and should not be used in clinical practice. Randomized clinical trials with adequate follow-up will be required to determine the ultimate role of less intense therapy for HPV-positive oropharyngeal cancer, he said.

Background

HPV-positive oropharyngeal cancer accounts for 60% to 70% of new cases of oropharyngeal cancer in the U.S., and the incidence has continued to rise. In general, HPV-positive disease has a more favorable prognosis as compared with HPV-negative oropharyngeal cancer.

At many institutions, standard therapy for newly diagnosed HPV-positive oropharyngeal cancer consists of total-dose radiotherapy of 70 Gy administered over 7 weeks, and concurrent cisplatin 100 mg/m2 for 3 weeks. The regimen achieves a high rate of pCR but causes substantial toxicity. Given the overall favorable prognosis of HPV-positive oropharyngeal cancer, many specialists have begun to ask whether reduced-intensity treatment might be just as effective with less toxicity.

Chera reported findings from a prospective phase II trial of reduced-intensity chemoradiation for low-risk HPV-positive oropharyngeal cancer. Eligible patients had diagnoses of T0-3, N0-2c, M0 disease associated with minimal or negative smoking history. Treatment consisted of a total radiation dose of 60 Gy administered in 2-Gy fractions daily for 6 weeks, plus concurrent weekly cisplatin 30 mg/m2. The regimen represented a 10-Gy reduction in the usual radiation dose and a 40% reduction in the usual chemotherapy dose, Chera said.

The primary outcome was pCR and was based on experience with usual high-dose therapy, which has been associated with a pCR rate of 87%. Patients undergo biopsy of the primary site 6 to 14 weeks after completing chemoradiation, as well as resection of any initially-positive lymph nodes. Secondary endpoints included toxicity, quality of life (QOL), and clinical outcomes of treatment.

Key Findings

The 86% pCR rate compared favorably with the 87% rate demonstrated by historical data. The overall results included pCR in 40 of 41 evaluable primary tumors (two of which were stage T0 at baseline) and pCR in the neck in 33 of 39 patients (four of whom had N0 status at baseline).

After a median follow-up of 21 months, all 43 patients remain alive and without evidence of disease, including 38 patients who have at least 1 year of follow-up.

Investigators evaluated QOL by means of an instrument developed by the European Organization for Research and Treatment of Cancer (EORTC QLQ H&N-35). Focusing on common adverse effects of chemoradiation for head and neck cancer, Chera noted that the severity score for dry mouth, sticky saliva, and swallowing all increased during the first 6 to 8 weeks, particularly dry mouth and sticky saliva.

The score for dry mouth peaked at about 70 on the 100-point scale and the score for sticky saliva rose to a maximum of about 60. Score for dry mouth remained at about 60 at 12 months, whereas the saliva score declined to about 40. The effect on swallowing was less severe, reaching a maximum of about 20 and then declining to less than 10 at 12 months.

Patient-reported symptoms exhibited a similar pattern as the dry mouth score averaged less than 0.5 (0 to 4 scale) at baseline, increasing to almost 2.5 at 6 to 8 weeks, and then declining to less than 2.0 by 1 year. Patient-rated swallowing difficulty was less than 0.5 at baseline, about 1.0 at 6 to 8 weeks, and slightly less than 1.0 at 1 year.

Physician-rated grade 3/4 toxicity and patient-rated severe/very severe toxicity included mucositis (34%/45%), pain (5%/48%), nausea (18%/52%), vomiting (5%/34%), dysphagia (39%/55%), and xerostomia (2%/75%).

Chera and colleagues have already closed enrollment for another phase II trial that will evaluate a reduced-intensity regimen that makes surgery optional, omits chemotherapy for patients with T1-2 N0-1 disease, and includes patients with as much as a 30 pack-year smoking history but who have a 5-year period of abstinence.

A planned “third-generation” phase II trial will evaluate the feasibility of cancer genetics risk-based stratification of patients and examine more specifically the question of whether reduced-intensity treatment is possible for patients with a >10 pack-year smoking history.

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

October, 2015|Oral Cancer News|

Throat and tongue cancers linked to sexually transmitted virus on the rise

Source: www.theage.com.au
Author: Julia Medew

The sexual revolution is producing a new wave of throat and tongue cancers among middle-aged people, who are falling victim to a rare side effect of the “common cold of sexually transmitted infections”.

A growing number of Australians with oropharyngeal cancer are testing positive to the human papillomavirus (HPV), suggesting it has caused their disease rather than smoking or heavy drinking – factors responsible for many head and neck cancers in the past. Oropharyngeal cancer is usually found in the back third of the tongue or the tonsils. In 2014, about 125 Victorians were diagnosed with it. Most were men.

An Australian study of 515 patients diagnosed with the condition between 1987 and 2010 found that the proportion of people with an HPV-related diagnosis increased from 20 per cent between 1987 and 1995 to 64 per cent between 2006 and 2010. Over the same period, the proportion of people diagnosed with throat cancer who had never smoked increased from 19 per cent to 34 per cent, suggesting HPV may overtake smoking and drinking as a cause of the cancer in future.

American doctors say more oral sex following the sexual revolution of the 1960s probably spread HPV to more people’s mouths and throats. Actor Michael Douglas said he believed oral sex was to blame for his HPV-related throat cancer in 2013. But Dr Matthew Magarey​, an ear nose and throat surgeon at Epworth and Peter MacCallum hospitals in Melbourne, said while HPV-related throat cancers were occurring in more people aged 40 to 60, it should not necessarily be associated with oral sex because scientists believe HPV may be transmitted through kissing or simple hand to mouth contact as well.

Up to 80 per cent of the adult population is thought to have had some sort of HPV infection during their life (there are more than 100 strains) and most of them will not have experience any symptoms. Many people clear the virus within months of getting it.

Dr Magarey said a tiny proportion of people will get an HPV-related cancer, such as cervical, anal, or throat cancer. He said HPV in the throat probably took 30 to 40 years to turn into a cancer in the minority of people it affects in that way. He said treatments were getting better for the cancer, which has a high survival rate if found early. Depending on the circumstances of the cancer, radiation, chemotherapy and sometimes surgery are used to treat it. While the surgery has been long and complicated in the past, Dr Magarey said a new robotic procedure available at Peter Mac and Epworth was helping surgeons remove cancers more precisely and in less time. This was reducing long-term recovery problems such as difficulty eating and drinking and swallowing.

Dr Magarey said the most common first sign of throat cancer was a lump in the neck that persists for more than two or three weeks. Symptoms can also include a sore throat that persists for more than three weeks and difficulty swallowing.

“If you have these symptoms, see your GP and get a referral to a qualified ENT surgeon who can properly examine the throat. Just looking in the mouth is not enough,” he said.

Dr Marcus Chen, a sexual health specialist with Alfred Health, said the Australian government’s HPV Gardasil vaccination program for young people will reduce such cancers in future. In the meantime, he said testing for HPV – the “common cold of sexually transmitted infections” – was not recommended because there is no way of treating the virus or preventing it from being passed on to others.

October, 2015|Oral Cancer News|

HPV Persistence Predicts Poor Prognosis in Head/Neck Cancer

Source: www.medscape.com
Author: Roxanne Nelson, RN, BSN
 

Among patients with human papillomavirus–positive oropharyngeal cancer (HPV-OPC), persistence of HPV following treatment is associated with a poorer prognosis.

Results of a new study show that the persistence of HPV16 DNA, detected in oral rinses after treatment has ended, may be predictive of disease recurrence.

In a cohort of 124 patients with HPV-OPC, HPV16 DNA was detected in oral rinses from 54% (n = 67) of patients at the time of their diagnosis. Following treatment, it was detected in only six patients after treatment, including five patients with persistent oral HPV16 DNA that was also detected at diagnosis.

All five patients with persistent HPV16 experienced disease recurrence, with three eventually dying of their cancer. Conversely, only nine of 119 patients without persistent oral HPV16 DNA developed recurrent disease.

“Our findings indicate that persistent HPV16 DNA in oral rinses may be a useful early marker of disease that has either recurred or never fully responded to treatment,” said first author Eleni Rettig, MD, of the Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.

“In the clinical setting, this could one day be a part of routine surveillance after treatment for HPV-positive oropharyngeal cancers, in addition to clinical examination and imaging,” she told Medscape Medical News.

The study was published online July 30 in JAMA Oncology.

Biomarker Potential?

In an accompanying editorial, Julie E. Bauman, MD, MPH, and Robert L. Ferris, MD, PhD, both of the University of Pittsburgh, in Pennsylvania, point out that HPV-specific biomarkers in oropharyngeal squamous cell carcinoma (OSCC) may be used to improve clinical outcomes, and “this pioneering study demonstrates an association between persistent oral HPV16 DNA detection and recurrence.”

But an ideal biomarker for recurrence, they say, should have a number of characteristics, including high sensitivity to identify the population with salvageable locoregional recurrence, a high positive predictive value (PPV) so as to avoid the economic, physical, and emotional costs of false-positive evaluations, and accuracy for detecting subclinical locoregional recurrence.

The prevalence of a positive oral rinse at diagnosis, however, was only 54%, and so the “low sensitivity of the assay, even with gross disease present, raises legitimate questions regarding its utility for diagnosing subclinical disease,” they say.

Of the six cases in which posttreatment HPV16 DNA was detected, five patients developed recurrent disease, representing a PPV of 83%, the editorialists write. When restricted to the five cases with persistent HPV16 DNA, the PPV then becomes 100%.

Although this looks impressive, they point out that “persistence can only occur in those who initially test positive — making this recurrence biomarker irrelevant for half of patients with HPV-positive” disease.

In addition, they add, the PPV can apply to any recurrence, including presentation with distant metastases, and “unfortunately, early diagnosis of disseminated OPSCC [oropharyneal squamous cell carcinoma] has not been associated with improved survival.”

“Operating characteristics, including low sensitivity, low confidence in the PPV, and high NNT [number needed to treat], preclude immediate clinical adoption,” say Dr Bauman and Dr Ferris. They add that incorporating an HPV-specific biomarker in future surveillance guidelines will require some refinement, including improved sensitivity and perhaps combining it with other serologic markers, such as HPV16 DNA or E6 antibodies.

“Meanwhile, the high negative predictive value of oral rinse HPV16 DNA detection raises the promise of deintensifying surveillance visits and/or costly imaging, particularly if on a prospective trial,” they conclude.

Dr Rettig agrees that more studies are needed before this test can be recommended. “For example, we need to understand when and how frequently to administer the test, what exactly we should do with a positive result, and what the cost-effectiveness would be, given the small number of individuals who actually have persistent oral HPV16 ― only five of 124 people in our study,” she said.

“We also can’t say for sure that all of the HPV16 DNA comes from tumor cells, and in some cases, it might just come from an oral HPV16 infection,” Dr Rettig explained. “For all of these reasons, right now, this test should only be used in the research setting until we have more information from additional studies.”

Associated With Recurrence

In this study, Dr D’Souza and colleagues examined HPV DNA detection in oral rinses after treatment for HPV-OPC and how it related to disease recurrence and survival.

This prospective cohort study included HPV-OPC patients diagnosed from 2009 to 2013 at four centers. Oral rinse samples were collected at diagnosis and after treatment (9, 12, 18, and 24 months after diagnosis) and were evaluated for HPV DNA. One or more posttreatment oral rinses were available for the 124 patients included in the study.

The median follow-up time was 33 (24-41) months, during which there were 14 recurrences and six deaths — all due to recurrent disease.

Two years after diagnosis, disease-free survival (DFS) was 92% (95% confidence interval [CI], 94% – 100%), and overall survival was 98% (95% CI, 93% – 99%).

The presence of HPV16 DNA in oral rinses at the time of diagnosis was not associated with either DFS (P = .15) or overall survival (P = .14), but on univariate analysis, persistent HPV16 DNA detection in oral rinses (eg, both at diagnosis and any time after treatment) was associated with a greater than 20-fold increased risk for recurrence (hazard ratio [HR], 29.7; 95% CI, 9.0 – 98.2) and death (HR, 23.5; 95% CI, 4.7 – 116.9).

It still remained associated with both DFS (adjusted HR [aHR], 35.8; 95% CI, 8.6 – 149.1) and overall survival (aHR, 16.1; 95% CI, 2.8 – 92.7) after adjusting for pack-years of smoking and tumor stage.

This research was supported financially by the Johns Hopkins Richard Gelb Cancer Prevention Award (Dr D’Souza), the Oral Cancer Foundation (Dr D’Souza), the National Institute of Dental and Craniofacial Research, and the National Institutes of Health Training in Otolaryngology grant (Dr Rettig). Several of the authors report relationships with industry, as noted in the article. The editorialists report no relevant financial relationships.

JAMA Oncol. Published online July 30, 2015. Abstract, Editorial

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

 

HPV vaccine now free for ‘at-risk’ boys and men under 26

Source: www.vancitybuzz.com
Author: Jill Slattery

vaccine

The government of B.C. announced this week the HPV vaccine for human papilloma virus will now be available free of charge to boys and men under age 26 who classify as ‘at-risk’.

Beginning in September, the free HPV vaccine program currently only available to young women will become available to men who have sex with males or who are “street-involved”.

“Providing the vaccine for all girls protects heterosexual boys as well, but leaves at-risk boys and young men unprotected. This change will address that gap,” said the province in a media release.

“The human papilloma virus is the most common sexually transmitted infection,” said Health Minister Terry Lake. “It can lead to serious health problems and could develop into an HPV-related cancer. Our vaccination program will help protect all young British Columbians from cancers and other diseases caused by HPV infection.”

HPV can be contracted by having sex with another person infected by the virus. According to the Centers for Disease Control and Prevention (CDC), HPV is “spread easily during anal or vaginal sex, and it can also be spread through oral sex or other close skin-to-skin touching during sex. HPV can be spread even when an infected person has no visible signs or symptoms.”

While HPV may cause little to no symptoms in some, it can lead to genital warts and certain kinds of cancer. In men, oropharyngeal cancers (cancers at the back of the throat) are the most common.

“In general, HPV is thought to be responsible for more than 90% of anal and cervical cancers, about 70% of vaginal and vulvar cancers, and more than 60% of penile cancers,” reports the CDC.

“It is clear that some men are more at risk for HPV related cancers than are others,” said Dr. Perry Kendall, B.C.’s provincial health officer. “As most of these infections are vaccine-preventable, extending B.C.’s HPV immunization program to this at-risk demographic is a cost-effective way to provide protection to the people who need it most.”

Men who have sex with other men carry a disproportionately high chance of contracting HPV.

The provincial HPV vaccine program uses the Gardasil vaccine, protecting from HPV types 16 and 18 that cause 70% of cervical cancers, 80% of anal cancers and other cancers of the mouth, throat, penis, vagina and vulva. It also protects against infection from HPV types 6 and 11 that cause about 90% of cases of genital warts.

Single Dose of HPV-16/18 Vaccine Looks to Be Sufficient

Source: www.medscape.com
Author: Jenni Laidman
 

A single dose of a vaccine against human papillomavirus (HPV) may prevent cervical cancer as effectively as the standard three-dose regimen, researchers concluded after analyzing the combined results of two large vaccine trials. The HPV vaccine in these studies was Cervarix (GlaxoSmithKline), which is effective against HPV strains 16/18.

If randomized controlled trials ultimately support the result of this post hoc analysis, it could broaden protection against cervical cancer in areas of the world where vaccination programs are hardest to administer and where cervical cancer is disproportionately burdensome, the study authors say.

“Even if you ignore the expense, the feasibility of implementing and getting back to individuals for a second and third dose is quite challenging, especially in places where there is no infrastructure,” coauthor Cosette Wheeler, PhD, Regents Professor, Pathology and Obstetrics and Gynecology, University of New Mexico Health Sciences Center in Albuquerque, told Medscape Medical News.

The studies are published online June 10 in the Lancet Oncology.

The possibility of a single-dose HPV vaccine is “a huge public health win,” coauthor Aimée R. Kreimer, PhD, Investigator, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, Maryland, told Medscape Medical News. “Even if one dose protects only against HPV types included in the vaccine formulation, if we vaccinated most girls, we would have the chance to reduce cervical cancer by around 75%.”

That’s the exciting part, Dr Wheeler added. “If we’re able to achieve success with one dose, or frankly even with two doses, that makes the possibility for worldwide prevention much greater.”

HPV type 16 is the leading cause of cervical cancer, responsible for about 50% of all cases, and HPV 18 is the second-largest cause, at 20%.The authors note that this research was carried out with Cervarix, and it is unclear whether the results would also apply to the other HPV vaccine that is available, Gardasil (Merck & Co.), which is active against several more HPV strains and is the product that is commonly used in the United States. Whether results of this trial have any bearing on Gardasil will depend on what’s driving the strong immune response to Cervarix, the authors suggest. Cervarix carries a proprietary adjuvant, which may be responsible for the immune response.

Surprise Over Efficacy Findings

The idea of the current post hoc analysis arose from results in the large randomized controlled Costa Rica Vaccine Trial, in which about 20% of participants received fewer than three doses of HPV-16/18 vaccine. “We were surprised to observe that efficacy was the same regardless of the number of doses received,” Dr Kreimer told Medscape Medical News.

That led to the post hoc analysis of the immunization results from the Costa Rica Vaccine Trial combined with results from the only other large phase 3, double-blind, randomized trial of HPV-16/18, for a total of more than 14,000 participants, ages 15 to 25 years, including about 7000 control subjects. The second trial, called PATRICIA (Papilloma Trial Against Cancer in Young Adults), took place in 14 countries. The analysis found that 4 years after vaccination, women who received the required three vaccine doses and women who received fewer than three doses — usually due to pregnancy or a colposcopy referral — were equally protected against HPV-16/18. Further, the analysis showed a potential benefit of cross-protection against closely related HPV strains 31/35/45 among women whose two doses were 6 months apart — a benefit previously seen only with three doses.

Four-year vaccine efficacy against HPV-16/18 in the combined analysis was 77% for the 13,296 (6634 case, 6662 control) women in the three-dose group, 76% for the 549 (273 case, 276 control) women in the two-dose group, and 85.7% for the 238 (138 case, 100 control) women in the single-dose group. Efficacy against the closely related HPV-31/33/35 was 59.7% for three doses, 37.7% for two doses, and 36.6% for one dose. When data for the two doses were analyzed according to dosing regimen, the cross-protective efficacy was 10.1% for those who received their second dose 1 month after the first and 68.1% for those who received the second dose at 6 months.

Antibody concentrations for two doses given 6 months apart were very close to concentrations for three doses, the research showed. One-dose vaccination titers at 6 to 48 months were lower than those for two or three doses, “but the titers were stable and several times higher than those identified for natural immunity,” the researchers write. “We can now infer that these lower, vaccine-induced antibody titers provide as strong HPV prevention as the titers from two or three doses, at least in the short term.”

Just how long these vaccines will provide protection still needs to be determined. “We know with three doses we can see the protection going out toward 10 years, and we hope that maybe the protection is lifelong,” commented Dr Wheeler. “That does not mean that we know we will never need a booster. And that doesn’t mean if we give less than three doses that we know about the longevity or durability of that protection. So that’s another piece of the puzzle.”

Although these results cannot be applied to Gardasil, Dr Wheeler notes that studies looking at Gardisil antibody titers after two doses look promising.

In an accompanying comment, Julia M.L. Brotherton, Medical Director, National HPV Vaccination Program Register, VCS Registries, East Melbourne, Victoria, Australia, commented: “These data suggest that one dose of bivalent HPV vaccine might be adequate to protect against HPV-16 and HPV-18 persistent infections and, therefore, probably disease. HPV-16 and HPV-18 cause more than 70% of cervical cancers and the vast majority of HPV-related cancers at other anatomic sites. If this finding is confirmed, it opens up a great opportunity to extend the reach of protection using HPV vaccines to more people than we would have previously thought possible.”

Four authors of the study are GSK employees and own shares and stock options in the company. Other researchers had financial or advisory relationships GSK, Roche Molecular Systems, Merck, and Sanofi Pasteur MSD. Dr Brotherton notes that she has been an investigator for investigator-initiated HPV epidemiology research grants partially funded by bioCSL/Merck, but this did not involve financial compensation.

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