Life Extension Magazine®
Most people associate viruses with the flu or common cold.
Few understand that viruses cause about 15% of all cancers.1,2
One such virus is oral human papillomavirus (HPV). It is present in 1 of every 9 American men.3
HPV mutates cellular DNA in a way that causes certain cancers.
In women, this usually manifests as cervical malignancies4 that can be screened for (Pap smear) and are easy to cure when caught early.5
In men, HPV infection is causing more head and neck cancers than it does cervical cancers in women. Head and neck cancers are not as easy to screen for and require toxic treatments.6,7
Head and neck cancers (oropharyngeal squamous cell carcinoma) are more common in men than in women. They have increased 300% in men over the past 20 years.3,7 A prime culprit is HPV infection.
For those who abstain from sex or are in monogamous relationships, their risk of HPV is lower. Those with multiple partners are at high risk, especially males.
This editorial describes risk factors behind head and neck cancers as well as what may be done to circumvent viral-induced malignancies.
Actor Michael Douglas was diagnosed with head and neck cancer in 2010.
As with other benevolent celebrities (like Suzanne Somers and Ben Stiller, who let the world know about their health issues), Michael Douglas went on national TV to warn that head and neck cancers are no longer confined to tobacco users.
Michael Douglas made it clear that his head and neck cancer was not caused by tobacco, but instead by his (promiscuous) lifestyle.
He described the chronic throat pain he endured during and after harsh radiation treatments, which appear to have been curative. Many patients undergo both surgery and radiation.
Jamie Dimon, CEO of JP Morgan Chase Bank, found himself in a similar predicament in 2014, and he has been apparently put into a complete response with conventional treatment.
Head and neck cancers have been historically linked to alcohol and tobacco use, but HPV is increasingly the underlying culprit.
What you need to know
Head and neck cancers are on the rise due to the spread of the human papillomavirus (HPV). HPV is commonly associated with cervical cancer. However, the truth is it has a greater risk of increasing head and neck cancers in men. Multiple steps can be taken to reduce your risk of HPV and its associated cancers.
Startling Statistics
More than 64,000 Americans (47,650 men/17,040 women) will develop head and neck cancer this year.8
Most are over age 50 when diagnosed.8
An estimated 13,000 deaths will occur from head and neck cancer this year.8
To put this in perspective, about 50,000 Americans die annually of colorectal cancer.9
Colorectal cancer death rates are declining for reasons that include better screening and healthier diets.9
Head and neck cancers are surging. Of the estimated 13,000 annual deaths from this malignancy, about 10,000 occur in men and 3,000 in women.8
Yet there is little advocacy for head and neck cancer prophylaxis or screening.
Prescription Anti-HPV Therapies
Some people at very high risk for HPV or who suffer from immune senescence may consider a dual drug approach that involves therapies that exert powerful immune activation with increased cytotoxicity against viral-infected cells.
One of these more aggressive anti-viral approaches might involve a regimen of low-dose interleukin-2 (1.8 million units) injected under the skin (subcutaneous) for 3 days a week, combined with the vitamin A analog drug tretinoin (10 mg every 12 hours, five days a week). This might involve 3 or more consecutive weeks every 6 months or so.27
The cost of interleukin-2 and tretinoin are outrageous and may only be considered for high-risk individuals. These drugs came off patent long ago, but price gouging by the pharmaceutical industry persists.
Risk Factors for Head and Neck Cancers
In earlier decades, head and neck cancers were rare except among those who used tobacco or indulged in excessive alcohol ingestion.10
Over the past several decades, physicians began noting a growing number of newly diagnosed patients with head and neck cancer that never smoked and were not heavy drinkers.11,12
What many of these head and neck cancer patients have in common are multiple sex partners. This enables a dangerous strain of human papillomavirus (HPV-16) to be continuously transmitted.12
The only encouraging news about HPV-induced head and neck cancers is that they respond better to conventional therapy than head and neck cancers caused by tobacco. (This is because HPV-16 damages DNA differently than tobacco.)11,13
This is of little consolation when one considers the pain of surgery, high-intensity radiation therapy, and the risks for secondary cancers that radiation creates.
Magnitude of Risk Increase
Tobacco and alcohol consumption are still the main risk factors for head and neck squamous cell carcinoma.14
Human papillomavirus (HPV) infection also plays a causative role in head and neck cancers that occur in the oro-pharynx.15-18
The oropharynx is part of the throat and includes the base of tongue, tonsils, soft palate, and the cavity behind nose and mouth that connects to the esophagus.
A study published in 2017 assessed the independent effects of tobacco, alcohol, and HPV infection on the risk of oropharyngeal cancer, a common head and neck cancer. The results found:19
- Heavy smoker (no HPV) →1.9-fold greater odds
- Heavy drinker (no HPV) →2.7-fold greater odds
- Heavy smoker (+ HPV) →49-fold greater odds
- Heavy drinker (+HPV) →51-fold greater odds
This magnitude of increased risk associated with HPV infection among heavy smokers and drinkers shown above is startling.
The question most readers of this magazine may ask is what about those who don’t smoke or heavily drink, but nonetheless are persistently exposed to HPV-16.
Another 2017 study provided unsettling data for some of us. After adjusting for smoking, alcohol, and low education, those infected with HPV-16 had a:20
- 4-fold greater odds of overall head and neck cancers
- 10-fold greater odds of oropharyngeal cancer
Oropharyngeal refers to the roof of the mouth, the tongue, tonsils, and part of the throat behind the mouth and nasal cavity.
HPV-16 infection is implicated as a causative factor behind oropharyngeal cancers, even in those who don’t smoke or heavily ingest alcohol.
In some regions, HPV strains are thought to cause up to 60% of oropharyngeal cancers. This has resulted in an increased incidence among younger non-smokers that has been equated to as “epidemic” by some investigators.21
How Some Young People Avoid HPV
Eleven million American men are now infected with oral human papillomavirus.3
According to a 2017 report, the most likely to be infected are those who have had multiple oral sexual partners or who also have genital HPV infection.3
When looking at current promiscuous sexual behaviors, a significant percentage of the male population is at risk for HPV-induced cancers.
Yet most of the public has no idea that cancer can be caused by this readily transmissible virus (HPV-16 and variants).
Younger people have access to the HPV vaccine that is partially effective in preventing cancers of the cervix, genitals, and anus, along with head and neck cancer. Some groups are vociferously against HPV vaccines because of side effect concerns.
Older individuals who have already been infected by HPV-16 do not appear to benefit from the vaccine.3
What Older People Should Do
Those who are in monogamous relationships or who abstain from contact with other people are at lower risk of persistent HPV infection.
Unlike chronic viruses (such as cytomegalovirus), a healthy immune system often clears HPV-16 before it inflicts enough DNA mutations to cause cancer.
For those who have had chronic HPV exposure, but follow healthy lifestyles, there is some encouraging news to report.
Our Life Extension® staff reviewed a large volume of data to ascertain if there were validated ways to protect against HPV-induced cancers.
To our surprise, the healthy diet and supplement programs most of you already follow appear to offer a degree of protection.
HPV-16 mutates DNA in ways that are different from the DNA damage inflicted by tobacco.
Nutrients like folate,22 lycopene,23 and cruciferous vegetable extracts (indole-3-carbinol24 and sulforaphane25) appear to help protect against viral-induced DNA damage.
We’ve long advocated the periodic use of cimetidine, a low-cost drug that requires no prescription, to boost immune function and suppress viral activity.26
Those who may be chronically exposed to HPV and other viruses may consider 800 mg of cimetidine each night for 1–2 months each year. Cimetidine should not be taken continuously as it can cause side effects in some people.
It is important to remember that HPV is often (but not always) cleared from the body. Persistent exposure to new HPV infections, however, results in chronic mutations to our cellular DNA that can lead to cancers.
Why Men Are More Vulnerable to Oral HPV Infection
HPV can survive in the flat, thin cells on the surface of the skin, cervix, vagina, anus, vulva, penis, mouth, and throat.7
The virus is spread through contact with infected skin, mucous membranes, and bodily fluids.7 This includes during intercourse or oral sex, as actor Michael Douglas pointed out years ago.
Virtually all sexually active people will acquire HPV at some point. The virus is usually wiped out by the immune system before it can sufficiently damage DNA to cause cancer.
In women, HPV infection usually sets off an antibody response that destroys the invader and then maintains immune cells that are ready to attack if HPV reappears.
Men do not usually mount this aggressive antibody response.
A study titled The HPV Infection in Men collected genital, anal, and oral samples from over 4,000 (unvaccinated) men between 2005 and 2009. These samples were analyzed for two high-risk HPV subtypes and two that cause genital warts.
For this analysis, a sub-cohort of 384 men were studied. They had any of these HPV-subtypes and had not produced antibodies at the time of detection.28
Within 36 months following HPV detection in this sub-cohort, only 35 produced anti-HPV antibodies.28
This meager response rate varied depending on the site of infection. Most disconcerting was that none of the orally HPV-infected men produced antibodies.
To reiterate, men in this study who were orally infected with HPV produced no anti-HPV anti-bodies.
This lack of antibody response reduced the ability of men to clear HPV and increased the risk of getting infected with the same HPV type again.
One of the researchers overseeing this study at the Moffitt Cancer Center (Tampa, Florida) said recurring infections in some people may be due to reactivation of dormant virus or from the spreading of HPV infection from one part of the body to another, or from something yet to be discovered.7
The science behind this HPV/cancer epidemic is still evolving. Men up to 26 years of age may benefit from a four-virus-based vaccine that reduces infection with HPV-6, HPV-11, HPV-16, and HPV-18.29
How Older Men Might Generate an Antibody Response
DHEA is a hormone that initially demonstrated immune-enhancing benefits, including improved antibody responses to vaccines.30
Subsequent studies yielded inconsistent results as it related to improving antibody response to vaccines administered to elderly persons (who all likely suffered immune senescence).31,32
As it relates to HPV infection, DHEA has been shown to inhibit cervical cell proliferation in a dose-dependent manner. One study found that DHEA induced cell death via apoptosis in HPV-infected cells. The authors of this 2009 study boldly concluded that “DHEA could therefore be used as an alternative in the treatment of cervical cancer.”33
An intriguing pilot trial published in 2003 studied the effects of intra-vaginal DHEA in women with low-grade cervical dysplasia, a precursor to cervical cancer.
In this study, 12 women with low-grade dysplasia were given 150 mg of intravaginal micronized DHEA daily. After 6 months, 10 of the 12 women (83%) had no evidence of dysplasia. The remaining 2 had normal exams showing atypical cells of undetermined significance. These results suggest that intra-vaginal DHEA may promote regression of low-grade cervical lesions.34
While these studies focused on cervical cancers, they provide intriguing clues for the many of our male readers who supplement with DHEA to help maintain immune competence.
With age, DHEA levels plummet. Men who take 25 mg of DHEA a day usually restore levels of this hormone back up to youthful ranges.
Women sometimes need only 15 mg of DHEA daily to maintain youthful DHEA levels.
As discussed in the box on the next page, many of the nutrients and supplements taken regularly by readers of this magazine appear to confer some protective effect against HPV-induced malignancies.
Multi-Vitamins Protect Against Cervical Cancer
Risk factors for cervical cancers include cigarette smoking and unhealthy diets.
A higher HPV load has been associated with 3.3-fold greater odds for cervical intraepithelial neoplasia, a diagnosable precursor to cervical cancer.48
In a meta-analysis by type of vitamin or antioxidant, a significant preventive effect on cervical neoplasm was found as follows:49
Nutrient | Less Chance of Cervical Neoplasm |
Vitamin B12 | 65% |
Vitamin C | 33% |
Vitamin E | 44% |
Beta-Carotene | 32% |
Another study showed that cervical intraepithelial neoplasia patients who took multivitamins had a lower HPV-viral load and decreased frequency of cervical intraepithelial neoplasia stage I (65% less chance) and cervical intraepithelial neoplasia stage II or III (89% less chance).48
More specifically, the following results were found for cervical intraepithelial neoplasia stage II or III in relation to common dietary supplements:
Nutrient(s) | Less Chance of Cervical Intraepithelial Neoplasia |
Multivitamins | 79% |
Vitamin A | 81% |
Vitamin E | 80% |
Calcium | 79% |
These studies provide good data for cervical cancer risk reduction, but what about head and neck cancers? A 2012 study evaluated a number of factors and stated:50
“Increased fruit and vegetable consumption has been repeatedly shown to be associated with a reduced risk of HNC [head and neck cancer]…There are a large number of compounds in plant foods that may influence the risk of cancer, including both micronutrients for normal metabolism and other bioactive compounds with unknown metabolic significance. Therefore, whether dietary supplements containing micronutrients found in plant foods would be effective chemopreventive agents is of considerable public health interest.”
Studies like this provide intriguing insights into potential ways of reducing head and neck cancer risk, but proactive steps should be taken to boost immune function, especially in those who have physical contact with multiple sex partners.
Other Pesky Viruses
HPV is not the only cancer-causing virus.
Epstein-Barr virus (EBV) has been implicated in Hodgkin’s lymphoma, as well as stomach and nasopharyngeal cancers.35-38 EBV is often a persistent viral infection.
Shingles is caused by a herpes virus that reactivates as we undergo immune senescence.39 Although the herpes virus that causes shingles lies dormant in our nerves before reactivation, shingles causes very painful skin lesions.
Another herpes-family infection most adults harbor is cytomegalovirus. This virus accelerates immune senescence by depleting our pool of naïve T-cells.40-43 Active cytomegalovirus infections decrease human lifespan by several years.44,45
As it relates to sexually transmitted viruses, HIV is what terrifies people most. Yet HIV is still relatively rare in most population groups.
Hepatitis B and C viruses cause liver cancer.46 (Hepatitis C is curable with drugs like Sovaldi®.)47
We at Life Extension are poring over newly published literature to identify better methods of boosting immunity and/or purging the body of chronic viral infections that worsen as immune function deteriorates with age.
An Overlooked Epidemic
According to Centers for Disease Control and Prevention (2013–2014), more than 45% of men are infected with genital HPV.51
Genital HPV is more common than the oral type. About 40% of women carry genital HPV.51
Genital HPV can cause cancer of the anus, penis, and vagina. Vaginal HPV causes about 70% of all cases of cervical cancer.52
Oral HPV infection is causing head and neck malignancy rates to surge, especially in men.
Many of you reading this may have little risk of HPV infection(s), while others have been exposed to numerous strains of cytomegalovirus, Epstein-Barr, and other viruses.
Aggressive immune system vigilance is imperative in higher risk individuals.
An article on page 66 of this month’s issue suggests non-prescription approaches to boosting immune function.
For longer life,
William Faloon, Co-Founder
Life Extension Buyers Club
References
- Morales-Sanchez A, Fuentes-Panana EM. Human viruses and cancer. Viruses. 2014 Oct 23;6(10):4047-79.
- zur Hausen H. Viruses in human cancers. Science. 1991 Nov 22;254(5035):1167-73.
- Available at: https://consumer.healthday.com/sexual-health-information-32/human-papillomavirus-hpv-news-756/1-in-9-american-men-infected-with-oral-hpv-727553.html. Accessed August 27, 2018.
- zur Hausen H. Immortalization of human cells and their malignant conversion by high risk human papillomavirus genotypes. Semin Cancer Biol. 1999 Dec;9(6):405-11.
- Available at: https://www.acog.org/patients/faqs/abnormal-cervical-cancer-screening-test-results. Accessed August 27, 2018.
- Available at: https://www.nbcnews.com/health/health-news/silent-epidemic-cancer-spreading-among-men-n811466. Accessed August 27, 2018.
- Available at: http://www.chicagotribune.com/lifestyles/health/ct-hpv-oral-cancer-in-men-20180312-story.html. Accessed August 27, 2018.
- Available at: https://www.cancer.net/cancer-types/head-and-neck-cancer/statistics. Accessed August 27, 2018.
- Available at: https://www.cancer.org/cancer/colon-rectal-cancer/about/key-statistics.html. Accessed August 27, 2018.
- Maier H, Dietz A, Gewelke U, et al. Tobacco and alcohol and the risk of head and neck cancer. Clin Investig. 1992 Mar-Apr;70(3-4):320-7.
- Available at: https://www.cancer.gov/types/head-and-neck/head-neck-fact-sheet. Accessed August 29, 2018.
- Rettig E, Kiess AP, Fakhry C. The role of sexual behavior in head and neck cancer: implications for prevention and therapy. Expert Rev Anticancer Ther. 2015 Jan;15(1):35-49.
- Dok R, Nuyts S. HPV Positive Head and Neck Cancers: Molecular Pathogenesis and Evolving Treatment Strategies. Cancers (Basel). 2016 Mar 29;8(4).
- Available at: https://ghr.nlm.nih.gov/condition/head-and-neck-squamous-cell-carcinoma#genes. Accessed August 27, 2018.
- Mehanna H, Beech T, Nicholson T, et al. Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer—systematic review and meta-analysis of trends by time and region. Head Neck. 2013 May;35(5):747-55.
- D’Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007 May 10;356(19):1944-56.
- Strome SE, Savva A, Brissett AE, et al. Squamous cell carcinoma of the tonsils: a molecular analysis of HPV associations. Clin Cancer Res. 2002 Apr;8(4):1093-100.
- Hocking JS, Stein A, Conway EL, et al. Head and neck cancer in Australia between 1982 and 2005 show increasing incidence of potentially HPV-associated oropharyngeal cancers. Br J Cancer. 2011 Mar 1;104(5):886-91.
- Farsi NJ, Rousseau MC, Schlecht N, et al. Aetiological heterogeneity of head and neck squamous cell carcinomas: the role of human papillomavirus infections, smoking and alcohol. Carcinogenesis. 2017 Dec 7;38(12):1188-95.
- Laprise C, Madathil SA, Schlecht NF, et al. Human papillomavirus genotypes and risk of head and neck cancers: Results from the HeNCe Life case-control study. Oral Oncol. 2017 Jun;69:56-61.
- Curry JM, Sprandio J, Cognetti D, et al. Tumor Microenvironment in Head and Neck Squamous Cell Carcinoma. Seminars in Oncology. 2014 2014/04/01/;41(2):217-34.
- Bai LX, Wang JT, Ding L, et al. Folate deficiency and FHIT hypermethylation and HPV 16 infection promote cervical cancerization. Asian Pac J Cancer Prev. 2014;15(21):9313-7.
- Sedjo RL, Roe DJ, Abrahamsen M, et al. Vitamin A, carotenoids, and risk of persistent oncogenic human papillomavirus infection. Cancer Epidemiol Biomarkers Prev. 2002 Sep;11(9):876-84.
- Jin L, Qi M, Chen DZ, et al. Indole-3-carbinol prevents cervical cancer in human papilloma virus type 16 (HPV16) transgenic mice. Cancer Res. 1999 Aug 15;59(16):3991-7.
- Bauman JE, Zang Y, Sen M, et al. Prevention of Carcinogen-Induced Oral Cancer by Sulforaphane. Cancer Prev Res (Phila). 2016 Jul;9(7):547-57.
- Available at: https://www.lifeextension.com/magazine/2001/3/report_tagamet/page-01. Accessed August 27, 2018.
- William Faloon’s Personal Experimental Protocol. 2018.
- Giuliano AR, Viscidi R, Torres BN, et al. Seroconversion following anal and genital HPV infection in men: The HIM study. Papillomavirus Research. 2015 2015/12/01/;1:109-15.
- Hillman RJ, Giuliano AR, Palefsky JM, et al. Immunogenicity of the Quadrivalent Human Papillomavirus (Type 6/11/16/18) Vaccine in Males 16 to 26 Years Old. Clinical and Vaccine Immunology. 2012;19(2):261-7.
- Degelau J, Guay D, Hallgren H. The effect of DHEAS on influenza vaccination in aging adults. J Am Geriatr Soc. 1997 Jun;45(6):747-51.
- Hazeldine J, Arlt W, Lord JM. Dehydroepiandrosterone as a regulator of immune cell function. J Steroid Biochem Mol Biol. 2010 May 31;120(2-3):127-36.
- Ben-Yehuda A, Danenberg HD, Zakay-Rones Z, et al. The influence of sequential annual vaccination and of DHEA administration on the efficacy of the immune response to influenza vaccine in the elderly. Mech Ageing Dev. 1998 May 15;102(2-3):299-306.
- Giron RA, Montano LF, Escobar ML, et al. Dehydroepiandrosterone inhibits the proliferation and induces the death of HPV-positive and HPV-negative cervical cancer cells through an androgen- and estrogen-receptor independent mechanism. Febs j. 2009 Oct;276(19):5598-609.
- Suh-Burgmann E, Sivret J, Duska LR, et al. Long-term administration of intravaginal dehydroepiandrosterone on regression of low-grade cervical dysplasia--a pilot study. Gynecol Obstet Invest. 2003;55(1):25-31.
- Pallesen G, Hamilton-Dutoit SJ, Rowe M, et al. Expression of Epstein-Barr virus latent gene products in tumour cells of Hodgkin’s disease. Lancet. 1991 Feb 9;337(8737):320-2.
- Lee JH, Kim SH, Han SH, et al. Clinicopathological and molecular characteristics of Epstein-Barr virus-associated gastric carcinoma: a meta-analysis. J Gastroenterol Hepatol. 2009 Mar;24(3):354-65.
- Khan G, Hashim MJ. Global burden of deaths from Epstein-Barr virus attributable malignancies 1990-2010. Infect Agent Cancer. 2014;9(1):38.
- Cao Y. EBV based cancer prevention and therapy in nasopharyngeal carcinoma. npj Precision Oncology. 2017 2017/05/15;1(1):10.
- Zerboni L, Sen N, Oliver SL, et al. Molecular mechanisms of varicella zoster virus pathogenesis. Nat Rev Microbiol. 2014 Mar;12(3):197-210.
- Tatum AM, Hill A. Chronic viral infections and immunosenescence, with a focus on CMV. Open Longevity Science. 2012;6:33-8.
- Fletcher JM, Vukmanovic-Stejic M, Dunne PJ, et al. Cytomegalovirus-specific CD4+ T cells in healthy carriers are continuously driven to replicative exhaustion. J Immunol. 2005 Dec 15;175(12):8218-25.
- van de Berg PJ, Griffiths SJ, Yong SL, et al. Cytomegalovirus infection reduces telomere length of the circulating T cell pool. J Immunol. 2010 Apr 1;184(7):3417-23.
- Meijers RW, Litjens NH, de Wit EA, et al. Cytomegalovirus contributes partly to uraemia-associated premature immunological ageing of the T cell compartment. Clin Exp Immunol. 2013 Dec;174(3):424-32.
- Wang GC, Kao WH, Murakami P, et al. Cytomegalovirus infection and the risk of mortality and frailty in older women: a prospective observational cohort study. Am J Epidemiol. 2010 May 15;171(10):1144-52.
- Savva GM, Pachnio A, Kaul B, et al. Cytomegalovirus infection is associated with increased mortality in the older population. Aging Cell. 2013 Jun;12(3):381-7.
- Bartosch B. Hepatitis B and C viruses and hepatocellular carcinoma. Viruses. 2010 Aug;2(8):1504-9.
- Available at: https://www.scientificamerican.com/article/we-now-have-the-cure-for-hepatitis-c-but-can-we-afford-it. Accessed August 28, 2018.
- Hwang JH, Kim MK, Lee JK. Dietary supplements reduce the risk of cervical intraepithelial neoplasia. Int J Gynecol Cancer. 2010 Apr;20(3):398-403.
- Myung SK, Ju W, Kim SC, et al. Vitamin or antioxidant intake (or serum level) and risk of cervical neoplasm: a meta-analysis. Bjog. 2011 Oct;118(11):1285-91.
- Li Q, Chuang SC, Eluf-Neto J, et al. Vitamin or mineral supplement intake and the risk of head and neck cancer: pooled analysis in the INHANCE consortium. Int J Cancer. 2012 Oct 1;131(7):1686-99.
- Available at: https://www.cdc.gov/nchs/products/databriefs/db280.htm. Accessed August 28, 2018.
- Available at: https://www.cdc.gov/cancer/hpv/basic_info/cancers.htm. Accessed August 28, 2018.