Human papillomavirus (HPV) and oropharyngeal cancer. An update on prevention from the CDC.

Human papillomavirus (HPV) can cause serious health problems, including genital warts and certain cancers. However, in most cases HPV goes away on its own before causing any health problems. The same types of HPV that infect the genital areas can also infect the mouth and throat. Some types of oral HPV can cause cancers of the head and neck. Other types of oral HPV can cause warts in the mouth or throat.

HPV can cause cancers in the back of the throat (oropharynx), most commonly in the base of the tongue and tonsils. These cancers are called “oropharyngeal cancers.” Cancer caused by HPV often takes years to develop after initially getting an HPV infection.  It is unclear if having HPV alone is sufficient to cause oropharyngeal cancers, or if other factors (such as smoking or chewing tobacco) interact with HPV to cause these cancers. 

Signs and symptoms oropharyngeal cancersmay include persistent sore throat, earaches, hoarseness, enlarged lymph nodes, pain when swallowing, and unexplained weight loss. Some individuals have no signs or symptoms.

Knowing whether one has cancer caused by HPV may help physicians determine the prognosis for survival.  Head and neck cancers caused by HPV infection tend to respond better to current treatments as compared to head and neck cancers caused by tobacco or alcohol use.  There are also new treatment options such as vaccine clinical trials and de-intensification radiation protocols available to patients whose cancers are caused by HPV.

About 7% of people in the USA have oral HPV. But only 1% of them have the type of oral HPV that is found in oropharyngeal cancers (HPV type 16). Oral HPV and cancers of the oropharynx are about 3 times more common in men than in women. About 8,400 people are diagnosed in the USA with cancers of the oropharynx caused by HPV. 

It is uncertain how people get oral HPV. Some studies suggest that oral HPV may be passed on during oral sex (from mouth-to-genital or mouth-to-anus contact) or open-mouthed (“French”) kissing, others have not. The likelihood of getting HPV from kissing or having oral sex with someone who has HPV is not known. One can reduce the risk of getting HPV by using condoms and dental dams during oral sex, since they serve as barriers, and can stop its transmission from person to person.

There is no FDA-approved test to diagnose HPV in the mouth or throat.  Medical and dental organizations do not recommend screening for oral HPV.

HPV vaccines that are now on the market were developed to prevent cervical and other genital cancers. It is possible that HPV vaccines might also prevent oropharyngeal cancers, since the vaccines prevent an initial infection with HPV types that can cause oropharyngeal cancers, but studies have not yet determined if HPV vaccines will prevent oropharyngeal cancers.

Psychological disorders ( including depression and PTSD) and social withdrawal in laryngectomees

The loss of voice and a decrease in physical functioning due to breathing through a stoma are known to result in long-term changes in daily and professional life. There is growing evidence that head and neck cancer patients including laryngectomees are more often anxious and distressed than other cancer patients. Prevalence rates of psychiatric problems in laryngeal cancer patients vary from 20% to 60 %, if nicotine dependence is taken included. Studies reported depression in 4-20% of head and neck cancer patients, anxiety disorder and phobia in 2 - 6%,  adjustment disorder in 4 - 13%, post traumatic stress disorder (PTSD) in 1 -2% and alcohol dependence in 5-33%.

Several recent studies from the University of Leipzig in Germany explored the role of psychological problems in laryngectomees.

Psychological disorders were diagnosed in about a quarter of patients during the first year after laryngectomee according to a new study by Keszte et al. These were evenly distributed among males and females. However, women suffered more often from PTSD and generalized anxiety disorder. Alcohol dependency developed in 80% of the patients who had acquired no voice 80% following laryngectomy. Only 7% of individuals with any mental disorder received psychotherapy one year after laryngectomy. None of the patients diagnosed with alcohol dependency received psychotherapy or psychiatric treatment.

Another study by Danker et al. found that more than 40% of larngectomees withdrew from conversation. Only one-third of all laryngectomees regularly took part in social activities. About 87% perceived stigmatization because of their changed voice and more than 50% felt embarrassed because of their tracheostoma. Almost one-third of the patients had increased anxiety and depression.

These studies illustrates that only one in twelve patients who suffered from psychological disorders following laryngectomy receive adequate psychotherapeutic support. Because mental health seems to be related to successful voice restoration, more effort is needed to promote speech rehabilitation after laryngectomy.  Also more programs are needed to combat alcohol dependency. The studies also highlights the urgent need for psychological and social support programs for laryngeal cancer patients. 

The Laryngectomee Guide is published

This practical guide is aimed at providing practical information that can assist laryngectomees and their caregivers in dealing with medical, dental and psychological issues. The guide contains information about the side effects of radiation and chemotherapy; the methods of speaking after laryngectomy; how to care for the airway, stoma, heat and moisture exchanger filter, and voice prosthesis. In addition it addresses eating and swallowing issues, medical, dental and psychological concerns, respiration and anesthesia, and travelling as a laryngectomee. 

A paperback, Kindle Edition, and e book of the guide are available.
The guide can also be viewed and downloaded (free).

Patient support groups can obtain free paperback copies. ( e mail a request to ib6@georgetown.edu)

Recent lectures by Dr. Brook

Itzhak Brook MD gave a Grand Rounds lecture on May 16, 2012 for the Department of Surgery at Scott & White Medical Center, Texas A&M College of Medicine in Temple Texas. The lecture entitled " The patient Experience as a Laryngectomee" was about his experiences as a patient with head and neck cancer. The topics discussed include dealing with the medical and psychological issues, voice rehabilitation and life challenges as a laryngectomee. The presentation can be watched on YouTube. 

Dr. Brook delivered the  J. Conley Medical Ethics Lecture, the Scholar Award keynote lecture at the opening ceremony of the Annual Meeting of the American Academy of Otolaryngology - Head and Neck surgery Foundation & OTO EXPO in Washington DC on September 9, 2012. His lecture is entitled " A Physician’s Perspective as a Throat Cancer Patient ". A description of the presentation was published in the Meeting Daily Newsletter. The presentation can be watched on YouTube.

                                   

A presentation entitled “ Patient Voices in Diagnostic Error in Medicine “ in Diagnostic Error in Medicine, 5^th international Conference of the Society to Improve Diagnosis in Medicine, John Hopkins School of  Medicine, Baltimore Maryland, November 13, 2012.

A Grand Rounds lecture entitled  "Preventing Medical Errors: a Physician's Personal Experience as a laryngeal Cancer" was delivered to the Department of Medicine Louisiana State University on April 16, 2013. The lecture can be read on line and It can be viewed on YouTube.

A Grand Rounds lecture entitled “A Physician’s Personal Experience as a Head and Neck Cancer Patient” was delivered to the Department of Medicine Veterans Administration Medical Center Washington DC, June 26, 2013. It can be viewed on YouTube.

A presentation entitled "Life Challenges of laryngectomees" was delivered to the Lost Cord Club in Cleveland Ohio on September 28, 2012, and the Louisiana State University Feist-Weiller Cancer Center in Shreveport, New Voice Club on April 17, 2013. The last lecture can be viewed on YouTube. Comments on the lecture are available.

Dr. Brook gave a talk at the 5th Annual David Nasto Memorial Oral Cancer Awareness Walk in New Jersey on September 22, 2012 . He also signed copies of his book "My Voice". All proceeding were donated to the Oral Cancer Foundation.

He also presented a talk in a symposium about medical errors in oncology at the American Society of Clinical Oncology (ASCO) Annual Meeting on June 3, 2012 in Chicago, Illinois. see picture below. 
The contents of the lecture was published in the ASCO Educational Book. A summay of the lecture was published at the ASCO Post. A news release about the symposium was published at the ASCO Daily News. 

Dr. Brook presented a lecture at the 8^th International Conference on Head and Neck Cancer in Toronto, Ontario, Canada on July 23, 2012. The talk's title was “ Putting the Personal Back in Personalized Cancer Therapy; A Physician’s Experience as a Head and Neck Cancer Patient”.

The Head and Neck Cancer Alliance (HNCA) booth in the International Society of Laryngectomee  Annual Meeting in Durham NC June 6-8, 2012. Copies of the book " My Voice" by I. Brook MD were given out to the attendees. In the picture: from left to right: John Groves Director of HNCA, Itzhak Brook MD, member of the HNCA Board of Directors, and Doug Ulery Marketing Director of HNCA.

Long-term use of Heat-Moisture Exchangers (HMEs) among laryngectomees: medical, social and psychological patterns

A study published in 2013 by Brook et al. evaluated the long-term use of HMEs and other accessories by laryngectomized patient and especially on the use of the Provox® Micron.

 After laryngectomy, pulmonary protection is mostly acquired by means of using a Heat and Moisture Exchanger (HME) that is placed on an airtight seal around the stoma. The effects of HMEs on tracheal climate have been well-described, and the filtration effect of an HME with electrostatic filter has been described . 

This study investigated long-term use of HMEs in laryngectomees. A questionnaire was sent to 195 laryngectomees of which 75 were returned. Over 85% of all respondents used an HME, of which 77% were compliant users (i.e. >20 hrs/day). Incidence of pulmonary illnesses (either prior of post-surgery) was about 25%. Over 90% of all respondents were heavy smokers prior to their laryngectomy. One-third of all respondents are regularly exposed to dusty environments. Compliant HME-users tend to use less external humidifiers and vaporizers, showing a better pulmonary status and less health-care costs. Regarding Quality of Life, patients using a FreeHands device tended to have the most social contacts (r=.251; p=.030).The prevalence of depression is high, pointing to an urgent need to recognize and treat psychiatric problems like depression and suicidal ideation in this patient group.

Provox^® Micron HME^™

Heartburn caused by gastric reflux is a risk factor for laryngopharyngeal cancer

Gastric reflux can reach the upper airway, inducing cellular damage in the epithelial lining. This may be a risk factor for development of laryngopharyngeal squamous cell carcinoma although the medical literature is inconclusive.Frequent heartburn caused by gastric reflux was found to increase the risk for development of throat cancer, and over-the-counter antacids medication may provide protection from it, according to a newstudy  published in the journal of Cancer Epidemiology, Biomarkers and Prevention.

Researchers from Brown University studied heartburn incidence and medication use in 631 patients with squamous cell cancers of the throat and vocal cords who were not heavy smokers or drinkers, matching them with 1,234 healthy controls.

The investigator found that individuals who had reported a history of frequent heartburn were 78% more likely to have cancer than those who did not. Those with frequent heartburn who took antacids reduced their risk for cancer by 41%, compared with those whose heartburn was not treated.

There was no reduced risk among those taking proton pump inhibitors (i. e., Prilosec, Nexium, Prevacid, Aciphex) or histamine H2 receptor antagonists (i.e., Pepcid, Tagamet, Zantac). However, this may be because those who took such medications were likely to have had severe acid reflux, and not because those drugs are ineffective. The authors recommended that further studies are needed to clarify the possible chemopreventive role of antacid use for patients with gastric reflux.

Michael Douglas shares his treatment experiences for throat cancer and its association with sexually transmitted HPV.

Michael Douglas underwent chemotherapy and radiation treatment in 2011 for stage four throat cancer. He described his difficult personal experiences on the road to recovery in a recent interview. Douglas was shaken when he was diagnosed with late-stage cancer in 2010 after it took his physicians nine months to make the diagnosis. In an interview with the Guardian newspaper, Michael Douglas said that the throat cancer he was diagnosed three years ago was associated with HPV human papillomavirus (HPV) which can be transmitted during oral sex. Through this revelation Douglas pushed the disease onto the mind of millions of Americans who may have become concerned about this cancer for the first time. 

His first symptoms were a sore tooth that resembled a dental infection. He was seen by a periodontist and an otolaryngologist who repeatedly gave him antibiotics without any effect on the pain. After the clinicians assured him that he is better he left to an overseas vacation and only upon his return did another physician discover a walnut-size tumor at the base of his tongue. A biopsy of the tumor lead to the diagnosis of a stage-four throat cancer.

Douglas immediately underwent a grueling eight-week program of chemotherapy and radiation. He was able to avoid a feeding tube but still lost 45 pounds in the process. During the radiation treatment, Douglas was too weak to move around, and stayed confined to a sofa at his home. He currently feels rejuvenated with a new lease on life and is be back at work making movies again.

                                                

                    Michael Douglas in 2011 while receiving chemotherapy and radiation

The HPV Type 16, is also known to cause cervical cancer in women. Unfortunately there no early oral screening test for HPV such as the Pap test. The lack of a screening test for oral HPV means that a doctor should be seen as soon as symptoms appear: a lump in the neck, a sore throat or ear pain that persists for two weeks.

There are currently no studies showing that vaccines to prevent cervical cancer from HPV Types 16 and 18,  also prevent HPV related oral cancer. However, these vaccines are recommend for boys and young men.

Most head and neck cancers are caused by tobacco and alcohol. The overall number of cancer caused by tobacco and alcohol are decreasing, while those associated with HPV are increasing. The cancer caused by HPV generally occurs near the base of the tongue; a difficult site to see and test.  

A saliva test can detect an oral HPV infection. However it is not very helpful because 85% of individuals may be colonized with a variety of HPV types and less than 1% of individuals with HPV 16 eventually develop throat cancer.

Currently about a quarter of head and neck cancer are caused by HPV and it is associated with 80% of tonsillar cancer. About 25,000 cases a year are diagnosed in the United States, compared with 226,000 lung cancers. However, it is growing in importance as smoking-related oral cancers decline.Patients with  positive cancer associated with HPV have a lower risk of dying compared to those with HPV-negative cancer.

The growing frequency in oral sex may have contributed to the increase in cancer caused by HPV. Men are twice as likely as women to get it, and it is more common among whites than blacks. Straight men are more likely to get the cancer than gay men perhaps because there may be more HPV in vaginal fluid than on the penis.

Human papilloma virus (HPV) as a cause of laryngeal cancer: new treatment options.

HPV-related head and neck cancers occur mainly in the oropharynx ( tonsils and the back of the tongue ).  However, a 2013 study from China found HPV infection, especially infection due to the high-risk type HPV-16, was found to be significantly associated with the risk of laryngeal squamous cell carcinoma.

Knowing whether one’s cancer was caused by HPV may help physicians determine the patient prognosis and survival.  Head and neck cancers caused by HPV infection tend to respond better to current treatments as compared to head and neck cancers caused by tobacco or alcohol use.  There are also new treatment options available to patients whose cancers are caused by HPV . These include vaccine clinical trials and treatment protocols that use less radiation and chemotherapy. These are easier for the patient to tolerate as they may generate fewer side effects.

The only way that head and neck cancers can be evaluated for the presence of HPV is to biopsy the lesion and test it for the presence of HPV DNA.  Patients who have already completed surgery, for head and neck cancer, can find out if their cancer is HPV related if the pathology sample is still available. 

Laryngeal cancer

Anaerobic and microaerophilic bacteria in the biofilm on voice prostheses

Voice rehabilitation with voice prostheses is a standard therapy in laryngectomized patients. Biofilm formation on the surface of the voice prostheses causes device failure and requires frequent replacements. Studies analyzing the biofilmof voice prostheses have mainly focused on fungi and aerobic bacteria. Anaerobic bacteria as an integral part of the biofilms on voice prostheses have not been investigated yet.

Betl et al of the Department of Periodontology, Bernhard Gottlieb School of Dentistry, Vienna, Austria,  performed aprospective pilot study on the occurrence of anaerobic and microaerophilic pathogens in biofilm formation on voice prostheses.

Biofilmsamples of 15 voice prostheses were analyzed using a polymerase chain reaction-based hybridization method, searching for the existence of 11 selected anaerobic and microaerophilic pathogens.

In 80% of the voice prostheses, at least one and up to 10 of the tested bacteria were identified. Fusobacterium nucleatumwas the most common isolate (73%). Other frequently occurring pathogens were Treponema denticola (40%), Tannerella forsythia (33%), and Eikenella corrodens (33%). There was no correlation between the number of identified bacteria and the indwelling times (mean, 127 days; maximum, 344 days; minimum, 22 days).

This is the first study showing the presence of anaerobic and microaerophilic potential pathogens as part of the biofilmformation on the surface of voice prostheses. Further studies are warranted to find out if these organisms may be responsible for accelerated biofilm formation and reduced lifetime of the voice prostheses.

Anaerobic biofilm

Laryngectomy is performed more often in patients with advanced laryngeal cancer

Zhu and colleagues recently investigated whether having a medical comorbidity influenced the choice of treatment of patients with advanced squamous cell carcinoma of the larynx. Comorbidity is the presence of an underlying pathologic condition that has an impact on a patient's total burden of disease. More than 2/3 of patients with cancer have a comorbid condition, and up to one-third of these patients have 2 or more, with hypertension, cardiovascular disease, and pulmonary disease among the most prevalent.

The study evaluated 16 849 patients from more than 1400 medical centers diagnosed with primary invasive advanced squamous cell carcinoma of the larynx between 2003 and 2008. They were selected from the National Cancer Database.

The study demonstrated that receipt of treatment (chemoradiation vs total laryngectomy) was significantly associated with comorbidity. Patients with comorbidity were more likely to have subtotal or total laryngectomy. Patients were also more likely to undergo laryngectomy if they had stage IV disease and if they had been diagnosed at a teaching or research institution. Patients were more likely to receive chemoradiation if they were diagnosed after 2003 or if they lived in a zip code with a high percentage of high school graduates.

The study is the first that demonstrates that patients with advanced laryngeal cancer with one or more comorbidities are more likely to receive surgery than chemoradiation compared with patients without any comorbidity. Previous studies have demonstrated better survival in patients with advanced laryngeal cancer who had been treated with surgery compared with those without.

This study supports the superiority of laryngectomy even in presence of comorbidity.  Even though patients with a comorbidity were less healthy initially their outcome was better after laryngectomy than those who received chemoradiation.