Recent advances in targeted treatment for oral cavity and oropharyngeal cancer

With greater understanding of the cellular changes that cause cancer, newer drugs that specifically target these changes have been developed. Targeted drugs work in a different way than regular chemotherapy agents. They also often have different (and usually less severe) side effects.

Nivolumab (Opdivo®) injection, for intravenous use, was approved by the FDA for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy. Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. Nivolumab treatment was proven in a phase 3 trial to significantly extend overall survival for patients with SCCHN.

Side effects include: fatigue, rash, itching, cough, upper respiratory tract infection, swelling of the extremities, shortness of breath, and muscle pain.

Cetuximab (Erbitux®) is a monoclonal antibody (which is a manufactured version of an immune system protein) that targets epidermal growth factor receptor (EGFR), a protein on the surface of certain cells that helps them grow and divide. Oral cavity and oropharyngeal cancer cells often have more than normal amounts of EGFR. By blocking EGFR, cetuximab can slow or entirely stop cell growth.

Cetuximab can be administered in combination with radiation therapy for some earlier stage cancers. For more advanced cancers, it can be combined with standard chemotherapeutic  drugs such as cisplatin, or it may be used by itself.

Cetuximab is administered by infusion into a vein (IV), generally once a week. Side effect of cetuximab include allergic reaction during the first infusion and skin problems such as an acne-like rash on the face and chest, headache, tiredness, fever, and diarrhea.

Several other drugs that target EGFR are now being studied as well, some of which are already being used to treat other types of cancers.

Extending the life span of tracheoesophageal voice prosthesis (TEP) by oral decontamination that reduces biofilm formation.

Somogyi-Ganss and colleges of the University of Texas MD Anderson Cancer Center, Houston, investigated the patterns of tracheoesophageal voice prosthesis (TEP) and oral colonization with microorganisms, and recorded changes in TEP device life after targeted decontamination between 2003 and 2013. 

Two subgroups were evaluated: (1) patients with microbial analysis of the TEP and the mouth were analyzed to identify patterns of common contamination, and (2) patients who were prescribed targeted oral decontamination with topical or oral antimicrobials on the basis of the microbial analysis of the VP were analyzed to evaluate effects on device life.

Among 42 patients, 3 patients had only fungal, 5 only bacterial, and 33 had colonization with multiple species of fungi and bacteria. In the TEP-oral micro-flora subgroup (n = 15), 7 had common microorganisms in the mouth and on the TEP. Among the decontamination subgroup (n = 23), 6 patients received broad spectrum rinse, 16 anti-fungal agents and 13 antibiotics, or a combination thereof. After targeted decontamination, the median device life of prostheses improved from 7.89 to 10.82 weeks (p = 0.260). The majority of patients with a short TEP device life in this pilot had colonization with multiple species of bacteria and fungi. TEPs rarely had fungal contamination alone (3 %), and non-Candida albicans species were more common than expected. For these reasons, the investigators explored the use of targeted decontamination regimens that were associated with 1.4-fold improvement in TEP duration.

These findings suggest that reducing the colonization of TEPs by microorganisms can extend their useful lifespan.

Association was found between Hepatitis C and Head and Neck Cancers.

Hepatitis C virus (HCV) infection is associated with liver cancer (hepatocellular carcinoma) and non-Hodgkin's lymphoma. After noting that many of their patients with head and Neck Cancers (HNCs) also have HCV infection, Mahale and colleagues of MD Anderson Cancer Center, Houston, TX, investigated whether such anassociation actually exists. In patients seen between 2004 to 2014.

The investigators compared 409 patients with HNCs to 694 with smoking-associated (lung, esophagus, or bladder) cancers seen between 2004 to 2014. The prevalence of HCV infection was higher in oropharyngeal cancer patients (14.0%) , and especially in HPV-positive ones (16.9%), and non oropharyngeal HNC patients (20.0%) than in control subjects (6.5%). A statistically significant association of HCV infection was found with non oropharyngeal (except nasopharyngeal) HNCs and HPV-positive oropharyngeal cancers.

The authors concluded that further studies are required to explore the possible interaction between HCV and HPV, and the association between HCV and other HPV-related malignancies.

Immunotherapy of HPV induced head and neck cancer (HNC)

Immunotherapy of HPV induced  HNC represents a new treatment approach that might allow clinicians to use conventional treatment at lower doses, and reduce treatment-related toxicity. Therapy is directed at  the oncoproteins E6 and E7 that are expressed by tumor cells.

Prophylactic vaccination against HPV  induces antigen-specific B cells that can  prevent initial infections. In contrast, therapeutic vaccines generate CD8+ HPV-specific T cell immune response against E6 and E7 oncoproteins. 

Their role in prevention of HPV-related oropharyngeal cancers is currently being evaluated, with one trial showing promising results.

Several vaccination therapies are under investigation in HPV-associated HNC. DNA vaccines produce non-living antigens able to induce cytotoxic T cell, and Th and B cell immunity. Several DNA vaccine trials targeting HPV are being tested in cervical cancer.

Peptide  vaccines incorporate amino acid sequences that are synthesized to form an immunogenic peptide molecule representing the specific epitope of a tumor-associated antigens that binds onto human leukocyte antigen. (http://www.ncbi.nlm.nih.gov/pubmed/14647479). Several peptide vaccines are under evaluation in HPV+ HNC..

Vaccination strategies involving Dendritic cells are also currently being assessed in HPV+ HNC. Activated DCs cells are injected back into the patient 5to kill the cancer (http://www.ncbi.nlm.nih.gov/pubmed/26351330). Several bacterial HPV vaccines targeting E6 and E7 have been developed. 

Finally, adoptive T-cell transfer (ACT) might be a promising immunotherapy strategy for HPV HNC; it involves harvesting and ex vivo expansion of the patient’s own tumor antigen specific T-cells. Subsequently, T-cells are re-introduced to the patient, with the view to enhance immunity and improve anticancer immune response.

It is hopeful that these novel immunotherapy strategies of HPV positive HNC will improve patient outcome.

History of smoking and long term outcome in head and neck cancer patients.

A new study by Peterson and colleagues investigated associations between a history of tobacco use and survival outcomes. The researchers from  the Department of Otolaryngology, University of Michigan Medical School, Ann Arbor, Michigan surveyed 687 previously untreated patients with cancer of the oral cavity (n = 271), oropharynx (n = 257), larynx (n = 135), or hypopharynx (n = 24). They explored the associations of tobacco use intensity (packs/day), duration (years of use), and timing before diagnosis with overall survival, disease-specific survival, and recurrence-free survival.

The study showed that cigarette use duration, timing, and intensity were significant predictors for all adverse outcomes. Never smoking and pack-years were not significantly associated with outcomes after adjustment for prognostic factors, such as stage, comorbidities, and human papillomavirus (HPV) status, which were strongly associated with clinical outcomes.

The authors concluded that their findings confirm the association between smoking history and survival and the importance of clinical variables in evaluating smoking as a prognostic factor. They also stated that timing, intensity, and duration of cigarette use should be considered with other prognostic factors when considering risk stratification for treatment planning.

Laryngeal Carcinoma patients’ outcomes can be improved by adding Cetuximab to radiotherapy

Laryngeal preservation and laryngectomy-free survival of patients with hypopharyngeal or laryngeal carcinoma, can be improved by addition of cetuximab to radiotherapy according to a recent study published by  Bonner et al. from the University of Alabama at Birmingham.

The authors examined the rates of laryngeal preservation and laryngectomy-free survival in a randomized trial involving patients with cancer of the larynx or hypopharynx. A total of 168 patients from 73 centers in the US and 14 other countries were randomized to cetuximab and radiotherapy (CRT; 90 patients) or radiotherapy alone (78 patients).

The researchers found the rates of laryngeal preservation (no need for laryngectomy) were 87.9 and 85.7% for CRT and radiotherapy alone, respectively, at two years. Median overall survival was 27 months in the CRT group and 21 months in the radiotherapy-alone group. There were no differences observed in overall quality of life, need for a feeding tube, or speech.

Sexual and non-sexual transmission of Human Papilloma Virus (HPV)

Human papillomavirus (HPV), is the most common sexually transmitted disease in the US and responsible for around 5% of cancers worldwide, most notably cervical and throat cancer. The virus can spread through sexual contact but non sexual transmission is also possible. A study by Myers et al. suggests that non sexual transfer can occur because HPV is resistant to many surface disinfectants and hand sanitizers that are alcohol based.

A report by Dahlstrom et al. has provided further evidence that HPV is not restricted to sexual intercourse and can also be spread via mouth-to-genital and mouth-to-mouth contact, with individuals who use tobacco being at the highest risk for infection.

Fakhry et al. demonstrated statistically significant relationships between current tobacco use and oral HPV-16 infection. This association may be due to the fact that smokers are more likely to have mouth ulcers and chronic inflammation that allows the virus to enter the oral mucosa and persist there. Because tobacco use may make HPV infections less likely to clear, smokers may have a higher risk of eventually developing oropharyngeal cancers. 

Understanding how HPV is transmitted is important because it can helps identify those who are most at risk for HPV infection and how they can protect themselves and their partners.

Combined effects of smoking and HPV16 in oropharyngeal cancer

A new study explored the effects of joint exposure impacts of smoking and HPV infection on oropharyngeal cancer risk. Specifically, the investigators studied if smoking confers any additional risk to HPV-positive oropharyngeal cancer.

Anantharamanet al.  examined the interaction between smoking and HPV16 in 1904 cancer patients and 3024 control from two large European multi-center studies. They observed that both smoking and HPV seropositivity were independently associated with oropharyngeal cancer. The joint association of smoking and HPV infection was additive suggesting they act as independent risk factors for oropharyngeal cancer.

An additional observation was that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. 

The authors concluded that the impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programs for primary prevention of head and neck cancer.

Good dental hygiene may reduce the risk of head and neck cancers

Daily tooth brushing and annual dentist visits may reduce the risk of head and neck cancers by a small margin, according to a recent study by Hashin et al. of the department of preventive medicine at Icahn School of Medicine at Mount Sinai in New York.

The researchers combined data from 13 past studies including a total of almost 9,000 oropharyngeal, hypopharyngeal, and pharyngeal cancer patients and more than 12,000 comparison subjects without cancer. The studies were done in the Americas, Europe and Japan. In all of them, oral hygiene was assessed based on gum disease or bleeding, missing teeth, daily tooth brushing, visiting a dentist at least once per year and whether a person wore dentures.

Individuals with fewer than five missing teeth, annual dentist visits, daily tooth brushing and no gum disease had lower risk than others of having head and neck cancer. Wearing dentures was not related to cancer risk. 

The indicators of oral hygiene/health used in the study are all connected with chronic irritation to the head and neck and are indicative of tooth wear, mechanical trauma, and general health maintenance.

The authors conclude that good oral hygiene, as characterized by few missing teeth, annual dentist visits, and daily tooth brushing, may modestly reduce the risk of head and neck cancer.

Acupuncture can help head and neck cancer patients' pain, dry mouth, lymphedema, neuropathy, tirednes, and nausea

Acupuncture can help head and neck cancer with managing some physical and emotional problems such as pain, feeling sick, and anxiety. It can also help individuals relax and improve their overall feeling of wellbeing.

Acupuncture is helpful in relieving some symptoms of cancer and the side effects of cancer treatment. It has sown to work in relieving chemotherapy related sickness, tiredness and cancer related pain.

Needling a variety of trigger and painful points, percutaneous electrical nerve stimulation, and osteo-puncture, along with whole body energetic acupuncture support, are approaches available to the acupuncturists.

Acupuncture is used to treat a wide range of pain conditions and some other symptoms. Some of the condition that acupuncture can be helpful that relate to head and neck cancer include:

• Acute and chronic pain control
• Dry mouth after radiation
• Muscle spasms, tremors, tics, contractures
• Peripheral neuropathy (after chemotherapy)
• Lymphedema after radiation (preliminary studies only)
• Anxiety, fright, panic
• Cancer and chemotherapy related tiredness
• Certain functional gastro-intestinal disorders (nausea and vomiting, esophageal spasm, hyperacidity, etc.)
• Headache, migraine, vertigo, tinnitus
• Cervical and lumbar spine syndromes and frozen shoulder
• Insomnia
• Anorexia
• Constipation  

Acupuncture performed by professionally qualified practitioners is generally very safe and has few side effects. Read more at Medical  issues in head and neck cancer section.

American Cancer Society key recommendations for head and neck cancer (HNC) survivorship care

The American Cancer Society published key recommendations for head and neck cancer (HNC) survivorship care. These are important recommendations that can improve patients’ care that includes surveillance for HNC recurrence, Assessment and management of physical and psychosocial long-term and late effects of HNC and its treatment (i.e. GERD, aspiration, fatigue, lymphedema, hypothyroidism, oral and dental care, taste problems, muscle dysfunction, speech and hearing ), psychological issues (Distress/depression/anxiety) , and nutrition.

To read the recommendations go to 

http://dribrook.blogspot.com/p/americancancer-society-key.html

Risk factors for pharyngocutaneous fistula after laryngectomy

Pharyngocutaneous fistula (PCF) is the most common surgical complication after total laryngectomy. Controversy still remains regarding the multiple risk factors implicated.

Dedivitiset al. surveyed the literature up to December 2013. The risk factors analyzed were age, sex, smoking habit, alcohol use, comorbidity, preoperative hemoglobin level, blood transfusion, preoperative tracheotomy, previous radiotherapy and chemoradiotherapy, primary tumor site, T classification, cartilage invasion, tumor grade, surgical margins, suture material, second layer of suture, reconstruction, tracheoesophageal prosthesis, and neck dissection. Of the 311 studies that were evaluated 63 met the inclusion criteria.

The author found that the risk factors for PCF were: chronic obstructive pulmonary disease (COPD), previous hemoglobin < 12.5 g/dL, blood transfusion, previous radio or chemotherapy, advanced primary tumor, suprglotic subsite, hypopharyngeal tumor site, positive surgical margins, and the performance of neck dissection.

Liang et al. who performed meta-analysis on on 16 studies found that tumor ssubsite, T stage, previous radiotherapy, postoperative hemoglobin < 12.5 g/dL, and surgical margins were the risk factors associated with the development of PCF.

Recognition of these factors can assist clinicians in expecting and treating PCF.

MRI of a pharyngocutaneous fistula after laryngopharyngectomy, and radial forearm free flap

Can proton pump inhibitors (PPI) cause dementia?

Proton pump inhibitors (PPIs) are widely used by head and neck cancer patients (including laryngectomees). PPIs have been shown to be potentially involved in cognitive decline including dementia. The use of PPIs has also been associated with chronic renal disease, and myocardial infarction.

A prospective cohort study from Germany evaluated 73 679 individuals 75 years of age or older that were treated with PPIs (omeprazole, pantoprazole, lansoprazole, esomeprazole, or rabeprazole) from 2004 to 2011. Those receiving regular PPI medication had a significantly increased risk of incident dementia compared with the patients not receiving PPI medication. This finding is supported by recent analyses on primary data and is in line with mouse models in which the use of PPIs increased the levels of β-amyloid in the brains of mice. 

A significant association of previous and current PPI use with vitamin B12 deficiency was found in a previous study in a population-based sample. Vitamin B12 deficiency has been shown to be associated with cognitive decline. In another study, PPIs were observed to enhance β-amyloid (Aβ) levels in the brains of mice by affecting the enzymes β- and γ-secretase. However, the underlying mechanism by which PPIs might influence the development of dementia is yet to be determined.

The authors concluded that avoidance of PPI medication may prevent the development of dementia. Randomized, prospective clinical trials are needed to examine this connection in more detail. 

Vocal cords grown from human cells

Laboratory grown vocal cord tissue that produces realistic sounds is a step toward creating new vocal cords for patients suffering from diseases such as cancer or injuries that damage their voice. Vocal cords that produce voice sounds have been grown in the laboratory from human cells. Details of the research are reported in the journal Science Translational Medicine.

Investigators from the University of Wisconsin in Madison harvested connective tissue and lining cells from the vocal cords of four patients whose voice boxes had been removed for medical reasons, and one human cadaver. They grew those cells onto scaffolds that produced strong elastic tissue similar to the one in the natural voice box.  After two weeks of allowing the cells to grow in the laboratory, the cells assemble into layers that resembled the structure of healthy vocal cords.

To test the freshly-grown tissue folds, scientists implanted them into one side of voice boxes taken from dogs, and attached them to an artificial windpipe and blew humidified air through them. When air was blown over the tissue it vibrated, producing sounds that had the same characteristics as those made by natural dog vocal cords. High speed digital imaging showed that the cords vibrated like natural tissue too. In follow-up studies using mice the transplants tissue were not rejected during a three months follow-up.  It is unlikely that replacement voice boxes will be created from vocal cord tissue from patients with cancer.  However, vocal cords could be created from stem cells that are turned into muscle and lining cells to form the cords.

Laboratory grown replacements for damaged vocal cords are still years away and more research is needed in animals to show that they work well and do not provoke an immune response, and the process must be performed with clinical grade cells before the implants can be tried in humans.

Normal vocal cords

High Suicide Rate for Patients with Head and Neck Cancer

Patients with head and neck cancer have more than 3 times the incidence of suicide compared with the general population, with rates highest among patients with cancers of the larynx and hypopharynx, according to a study published by JAMA Otolaryngology-Head & Neck Surgery.

Dr. Chan Woo Park R, M.D., of Rutgers New Jersey Medical School, Newark, and colleagues examined the incidence rate, trends, and risk factors of suicide in patients with cancer of the head and neck between 1973 and 2011. Compared with the suicide rate of the general population, the researchers found that patients with head and neck cancer have more than 3 times the incidence of suicide. Suicide rates were higher in those treated with radiation alone compared with those treated with surgery alone.

There was a nearly 12-fold higher incidence of suicide in patients with hypopharyngeal cancer and a 5-fold higher incidence in those with laryngeal cancer. The authors suggested that this may be linked to these anatomic sites’ intimate relationship with the ability to speak and/or swallow and that loss of these functions can dramatically lower patients’ quality of life. It is possible that the increased rates of tracheostomy dependence and dysphagia [difficulty swallowing] and/or gastrostomy tube dependence in these patients are exacerbating factors in the increased rate of suicide observed.

The authors recommended that additional research and effort should also be devoted to the psychological toll that the cancer, treatments, and resulting morbidity have on patients.

Persistence of HPV in saliva of patients with oropharyngeal carcinoma predicts recurrence

Human papillomavirus–related oropharyngeal carcinoma (HPV-OPC) is increasing in incidence in the United States. Although HPV-OPC has favorable prognosis, 10% to 25% of HPV-OPCs recur. Detection of human papillomavirus (HPV) DNA in oral rinses is associated with HPV-OPC, but its potential as was unclear.

Rettig et al. determined whether HPV DNA detection in oral rinses after treatment for HPV-OPC is a  prognostic biomarker that  associated with recurrence and survival.

The investigators studied 124 patients with HPV-OPC.  Oral rinse samples were collected at diagnosis and after treatment (9, 12, 18, and 24 months after diagnosis), and evaluated for HPV DNA.

Oral HPV type 16 (HPV16) DNA was common at diagnosis (67 of 124 participants [54%]). Oral HPV16 DNA persisted in only 6 participants after treatment (5%).  Two-year disease-free survival (DFS) and overall survival (OS)  were 92%  and 98%. Persistent oral HPV16 DNA was associated with worse DFS and OS . All 5 participants with persistent oral HPV16 DNA developed recurrent disease, 3 with local disease involvement. In contrast, just 9 of 119 participants (8%) without persistent oral HPV16 DNA developed recurrent disease, only 1 (11%) with local disease involvement. Median (range) time from earliest posttreatment oral HPV16 DNA detection to recurrence was 7.0 (3.7-10.9) months.

This study illustrates that although HPV type 16 DNA in oral rinses is common at diagnosis, it is rare after treatment for HPV-OPC. Detection of HPV16 DNA in oral rinses after treatment for HPV-OPC may be a useful adjunct to current post-treatment tumor surveillance strategies, potentially facilitating earlier diagnosis of progressive or recurrent HPV-OPC. This may enable earlier intervention and the administration of proper surgical and medical treatment.

The psychosocial impact of a total laryngectomy on the patient and their partners

A recent study by Offerman et al. from the Netherlands evaluated the psychosocial impact of a total laryngectomy (TL) on the patient and their partners.  The  study (http://www.ncbi.nlm.nih.gov/pubmed/25631352 ) surveyed 151 laryngectomees and their partners inquiring about their quality of life. A variety of psychosocial problems are reported by partners of laryngectomees, such as mood disorder, feelings of hopelessness, fear for losing their life companion and caregiver burden.

The investigators found that a considerable number of partners of laryngectomees experience a psychosocial impact of the consequences of the TL, specifically on their social life (35%) and on their sexual relationship (31%). Also, the tendency of other people to neglect their laryngectomized life companion, affects more than half of the partners negatively. Clinical levels of anxiety and depression were found in around 20% of the partners. TL has a negative effect on the sexual functioning for more than 30% of both laryngectomees and their partners, the communication for about one fifth of both laryngectomees and partners, and the feelings of dependency of the partner for one third of the laryngectomees.

The authors recommended that health care professionals should screen not only the patients but also their partners for need of support to deal with sexuality and intimacy. 

The Laryngectomee Guide is available

The 170 pages guide provides practical information assisting 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; and 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 Guide is available as paperback, Kindle Edition, and eBook.
To obtain a free paperback copy file this form and fax it to 414 227 9033. Alternatively it can be mailed to J. Harrison 11390 W. Theo Trecker West Allis WI 53214. It can also be requested by e mailing customersupport.us@atosmedical.com or calling 1-800-217-0025.

To obtain a free e book copy of the Guide in English click this link.
To obtain a free e book of the Guide in Turkish click this link.
To obtain a free copy of the Guide in Russian click this link. 
To obtain a free copy of the Guide in Italian click on this link.

The guide is endorsed by the American Academy of Otolaryngology-Head and Neck Surgery and the Society of Otorhinolaryngology and Head-Neck Nurses, Inc. 

Reviews of the Guide (see all reviews):

March 8, 2014

This book is a great resource for patients, families, health care providers, and medical and speech pathology students. It is a comprehensive guide to understanding and managing the issues associated with laryngectomy surgery and radiation treatment. It provides the unique perspective of Dr. Brook, a laryngectomee, physician, and patient advocate. Thank you Dr. Brook for all of your wonderful contributions to the laryngectomee community. As a speech pathologist in the field, I highly recommend this book.

Meryl Kaufman M.Ed., CCC-SLP, BRS-S

The Emory Voice Center, Emory University

Department of Otolaryngology Head and Neck Surgery

Atlanta, GA

March 10, 2015

Dr. Brook,

Your book has become an excellent resource that we now use in our facility for all our laryngectomy patients.  It now has replaced the previous educational materials we used to provide the patients.  Thank you so much for your rich contribution!

Ginny Chapa, CCC-SLP

Mayo Clinic Florida

Jacksonville Florida

See comments from laryngectomees who got the laryngectomee Guide:

• Yes, it's worth the time to order a copy.
• Yes. When in Beth Israel in NYC having my operation, my team of interns all carried copies of Dr Brook's books with them on rounds.
• Helped us many times !! Three years July 8th and I still use it to refresh .
• I wish I would have had that book right after my surgery instead of 2 years later. I still learned more from the book than I was offered from the surgeon and hospital.
• Yes indeed
• great reference! get it!!
• Yes. Lots of good information. And I got Jim Lauder's Dad's book when I was in the hospital from the speech therapist.
• Yes and yes Many many times!!
• Has helped me very much. In fact, I got the book about two weeks before my surgery.

Input from Tony Branch, laryngectomee since June 2016:

The very best resource I've seen is THE LARYNGECTOMEE GUIDE by Dr. Itzhak Brook M.D. Dr. Brook is not an ENT or an otolaryngologist, but an accomplished pediatrician on the staff at Georgetown Medical Center. However, he himself went through the very same experience that most of us have coped with, His book is written from a patient's perspective. From

first initial diagnosis to methods of speaking after the operation, Dr. Brook covers it all in easily language understandable to the layman. At the same time, he also has that invaluable medical background.

This has been an extremely important resource for me these past few months.

Initial surgical therapy for advanced-stage laryngeal cancer may increase survival.

A single academic center performing a high rate of surgical therapy, including total laryngectomy, to treat advanced-stage laryngeal cancer had a higher 5-year survival rate than national levels in a small study. Dr Blake Joseph LeBlanc, of Louisiana State University (LSU) Health-Shreveport and co-authors evaluated survival rates at their institution for primary surgical treatment of advanced-stage tumor with outcomes in the National Cancer Database (NCDB).

 In an analysis of 165 patients with laryngeal cancer in the LSU Health tumor registry from 1998 to 2007, 48 (29%) had clinically early-stage (I/II) disease and 117 (71%) had advanced-stage (III/IV) disease.

Of the 117 patients with advanced-stage disease, 64 (55%) underwent primary surgical therapy to include total laryngectomy or pharyngolaryngectomy .Data from the NCDB shows the national rate of laryngectomy declined from 60% in the 1980s to 32% in 2007.

Five-year survival for stage IV was at LSU was 56% compared with 32% nationally.

The authors noted "This study suggests that initial surgical therapy for advanced-stage disease may result in increased survival compared with organ preservation".

Better survival even after disease progression in HPV-positive head and neck cancer

Human papillomavirus (HPV)-positive tumor status is associated with a significantly better rate of overall survival in patients with oropharyngeal squamous cell carcinoma (OPSCC) that has progressed, according to Carole Fakhry, MD, and colleagues of Johns Hopkins Medical Center, Baltimore, Maryland.

Previous studies has shown reduced risk of cancer progression in patients with newly diagnosed local-regionally HPV-positive OPSCC. However, no information was available regarding the role of the HPV status in overall survival after cancer had progressed.

The retrospective study evaluated 181 patients with stage III-IV OPSCC, and included 105 who were HPV-positive and 76 who were HPV-negative.

Even though no difference was found in the median time to progression in relation to the HPV tumor status (8.2 vs 7.3 months; P = .67), HPV-positive OPSCC had significantly improved rates of overall survival at 2 years compared with HPV-negative patients (54.6% vs 27.6%; P< .001).

Factors significantly associated with increased risk of death included high tumor stage (T4 vs T2-3) at diagnosis, fewer cisplatin treatment cycles (≤1 vs 2-3), and distant versus local/regional recurrence. Smoking was also an important risk factor, with the risk of death after progression increased by 1% per cigarette pack-year at diagnosis (P = .002).

Significant reductions in the risk of death were associated with HPV-positive tumor status and undergoing salvage surgery. The overall rate of mortality was reduced by 50% in individual with HPV-positive tumors.

Sites of HPV oral cancer

HPV-positive squamous cell carcinoma of the oropharynx linked to later onset distant metastasis

Squamous cell carcinomas of the oropharynx (SCCOP) associated with human papillomavirus (HPV) usually have better outcomes that those not associated with HPV.  Patients with these cancers experience a later onset of distant metastasis and more metastatic sites in atypical locations, according to a new study by Samuel Trosman, MD and colleagues, of the Cleveland Clinic, Cleveland, Ohio. 

The study illustrated that even though the rates of distant metastasis is similar between patients with HPV-positive and HPV-negative SCCOP, distant metastases occur significantly later and involves more body sites. The researchers evaluated 285 patients with Stage III to IV SCCOP who were treated with chemo-radiation therapy between 2002 and 2013. Among the patients, 27 of 245 (11%) HPV-positive and 8 of 40 (20 %) HPV-negative patients developed distant metastases.

The radiation therapy regimen for the patients was either 3-dimensional radiotherapy or intensity modulated radiation therapy with doses from 66 to 79 Gy. Concurrent chemotherapy consisted of cisplatin, cisplatin/5-fluorouracil, or cetuximab.

Even though the distant metastasis rate between the HPV-positive and HPV-negative groups was similar, the mean time to develop the distant metastasis was significantly longer after the completion of treatment for HPV-positive patients (21.6 months) than for HPV-negative patients (7.0 months; P = .03).

The most common site of metastasis in both HPV-positive and negative individuals were the lung followed by bone. Patients who were HPV-positive had significantly higher average numbers of involvement in metastatic subsites compared with HPV-negative patients (2.0 vs 1.1; P = .026).

Among HPV-positive patients, 21 of 27 (78%) had  >1 metastatic site, and 12 (44%) had distant metastases involving >1 organ system, compared with only 1 of 8 (12.5%) HPV-negative patients. Spread to less typical metastatic sites occurred more often  in HPV-positive patients, and included liver (6), intra-abdominal lymph nodes (3), brain (2), pleura (2), and peritoneum (1). Local treatment failure occurred more often in HPV-negative patients (3 of 8  or 38%) compared to HPV-positive patients (4 of 27 or 15%).

 Sites of  oropharyngeal cancer caused by HPV

The Laryngectomee Guide is published

The 170 pages 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; and 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 Guide is available as paperback, Kindle Edition, and e book.
To obtain a free e book copy of the guide click this link.

The guide is endorsed by the American Academy of Otolaryngology-Head and Neck Surgery and the Society of Otorhinolaryngology and Head-Neck Nurses, Inc. 

Dustin Hoffman treated for throat cancer

Oscar-winning actor Dustin Hoffman, has been successfully treated for throat cancer and is "feeling great," his spokeswoman confirmed to People magazine. His publicist said the actor had been "surgically cured" after his cancer was detected at an early stage. No further details were provided though Hoffman is thought to be recovering well and is in good health.

The two-time Oscar winner and director, 75, will undergo doctor-recommended preventative treatments to minimize the chance of a recurrence of cancer in the years ahead.

Dustin Hoffman lighting a cigarette

No increased risk of infection for sex partners of individuals with HPV-related oral cancers

Human papilloma virus (HPV)-related oral cancers are rising in prevalence among white men in the US, and fear of transmitting the virus can lead to anxiety, divorce, and curtailing of sex and intimacy among couples. Persistent oral HPV infections are a risk for developing oropharyngeal cancers, located at the base of the tongue, tonsils, pharynx and soft palate.

A multicenter, pilot study performed by Johns Hopkins investigators found that spouses and long-term partners of patients with mouth and throat cancers related to infection with the HPV appear to have no increased prevalence of oral HPV infections. The study’s results suggest that long-term couples need not change their sexual practices.

The researchers conducted surveys and took oral rinse samples from 166 male and female patients with HPV-related oropharyngeal cancers and 94 spouses and partners. More than half of patients had at least one type of HPV DNA detectable in their oral rinses, including HPV16, the viral type most commonly associated with oral and other cancers. After a year, only seven patients (6%) still had oral HPV16 DNA detectable.

Of the 94 spouses/partners, six had oral HPV infections (6.5 %). These infections were not detectable one year later. No oral cancers were detected among 60 spouses/partners who underwent a visual oral examination.

The investigators concluded that oral HPV prevalence among partners was comparable to rates observed among the general population, and even though long-term spouses and partners have been exposed to HPV they cleared the virus. They also concluded that more research is needed to determine the timeline of progression for HPV-related oral cancers and how HPV is transmitted and suppressed by the immune system.

Importance of patient reporting new symptoms in the early detection of head and neck cancer recurrence

A recent study by Nisa and colleagues from Sion, Switzerland, evaluated the value of patients' reported symptoms as an indicator of tumor recurrence after definitive treatment for head and neck squamous cell carcinoma. Cancer recurrence occurred in 30 of the 101 patients included in the study had local and/or regional recurrences.

One-third of all patients had early stage, and two-thirds had advanced-stage tumors; two-thirds received only single treatment modality (i.e., surgery, radiation) and one-third had multiple treatment modalities. Most patients were male, with a mean age of 61.5 years (range, 29-85 years), and had at least one risk factor (tobacco and alcohol).

New-onset symptoms had the best correlation with cancer recurrences. Localized pain, pain on swallowing (odynophagia), and impaired ability to produce voice (dysphonia) were independently correlated with recurrences. Correlation was better between 6 to 12 and 18 to 21 months after therapy and in patients initially treated with only one type of therapy (i.e., surgery or radiation alone).  Primary stage and tumor site had no effect on the correlation.

The study underlines the importance of close and continuous follow-up after treatment of head and neck cancer especially during the first 2 years. It also illustrates that patient input and vigilance in reporting new symptoms are instrumental in diagnosing cancer recurrence. Close follow-up has other important goals, especially the identification and management of treatment-related complications and psycho-social support.