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Many Skin Cancers and Pre-Cancers Are Caused by HPV and Sunlight

We have known for many years that the Human Papilloma Virus (HPV) causes almost all warts on the skin, most head and neck cancers, and almost all cervical cancers. Now we find that HPV also causes the common skin pre-cancers called actinic keratoses, which can develop into squamous cell skin cancers that can spread through other parts of the body (Trends in Microbiology, January 2011). More than 60 million Americans suffer from actinic keratoses, scaly areas on sun-exposed skin primarily on the face, ears, scalp, neck, and dorsal surface of the hands.

Most actinic keratosis cells are infected with HPV, the viruses that cause warts (1 - see list of references below). Dr. Eggert Stockfleth, of the Charité Hospital in Berlin, found specific types of HPV (21, 5, 8, 16 and 18) that convert normal skin to the pre-cancerous actinic keratoses, which may then progress to become squamous cell cancers (2).

Recent research shows that these skin pre-cancers are caused by a combination of cumulative exposure to sunlight and HPV, which can be acquired through sexual contact (3).

How skin cancer starts:
Chronic exposure to ultraviolet light damages DNA in skin cells. Your immunity tries to repair this damage, but the Human Papilloma wart viruses can prevent your immunity from repairing the DNA. Most of the time when your DNA is damaged, the cells die because they have a programmable cell death called apoptosis. However, the HPV virus prevents DNA from healing and also prevents the programmable cell death that would have removed the damaged cells (4). Then you develop scaly areas and bumps on your skin called actinic keratoses. With further exposure to sunlight, HPV can cause these damaged cells that do not die to develop into squamous cell skin cancers that can spread through your body.

The more different HPV viruses you have, the more likely you are to develop skin cancers:
More than 150 different types of HPV exist. Some types of HPV (Types 8, 24 and 76) are far more likely to cause skin cancer than others. The ones most likely to cause cervical cancers are types 16, 18, 52 and 59. They are also the ones that persist the longest, and are most likely to cause cancers and abnormal PAP smears.

A person acquires these viruses usually, but not always, from a sexual contact, and then a person's immunity usually clears the virus in six to eight months. However, the more viruses a person picks up from other people, the more likely he or she is to go on to suffer squamous cell skin cancers (5).

The more sexual partners you have, the more likely you are to acquire and keep the cancer-causing HPV virus (6). Men 18 to 70 years old who were free of both HIV and cancer had HPV cultures taken every six months from several places on the penis and scrotum. Among the 1159 men, the incidence of new genital HPV infection was 3.8 percent every six months. Those who had the most sexual partners had the most HPV infections that cause cancer.

Positive cultures for HPV persisted for an average of 7.5 months, and for HPV 16, the type more likely to cause cancer, for 12.2 months. The more partners a person has, the less likely he is to clear the virus. Older people clear HPV faster than younger ones, probably because they have fewer new partners.

Most hpv infections go away:
If you don't acquire any of the other 150 HPV types from additional contact, most HPV infections appear to clear themselves without treatment (7). DNA tests of HPV show that 70 percent of women clear HPV infections in their cervix and vaginas within one year, and only nine percent continue to be infected after two years (8). A summary of several studies shows that 90 percent of HPV tests become negative in about two years.

The current theory is that you become infected with HPV, usually through sexual contact, and it can disappear without treatment, as cultures fail to find it. We do not know if the virus really goes away, but we usually cannot find it. However, some people never clear the high-cancer-risk types of HPV and it is the persistent infections that can lead to skin pre-cancers and cancers (9).

Additional exposure to HPV:
Infected people who continue to have the most sexual contacts are the ones most likely to continue to be infected with HPV. Each additional sexual exposure increases your chances for acquiring additional HPV viruses and the specific viruses that cause cancer.

You can have several different HPV virus types at the same time. Acquiring immunity to one type of HPV does not protect you from becoming infected with another type of HPV in the future. It is likely that the more HPV viruses that infect you and the more sunlight that damages your skin, the more likely you are to develop skin cancer.

How do you get HPV?
The most common way to acquire HPV is through rubbing skin on skin, usually through sexual contact, but any type of rubbing skin on skin has been associated with an increased risk. Non-penetrating skin-on-skin contact has caused HPV transmission even in virgins (10). The virus has repeatedly been found underneath the fingernails, so shaking hands can, at least theoretically, transmit the virus (11). Furthermore, HPV can be transmitted non-sexually from a mother to her child (12). HPV was found in up to 50 percent of pubic and anal hairs removed from patients with genital warts (13).

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Condoms:
Condoms do not offer complete protection against HPV since any skin-to-skin contact can result in transmission of the virus (14). The virus can also pass around condoms in body fluids, such as saliva, semen and vaginal secretions.

New sexual partners:
You are most likely to acquire HPV from a new sexual partner, rather than an old one, as healthy people usually clear the virus from their bodies in six to eight months. Each new partner can give you new HPV infections and the more HPV viruses you have at one time, the more likely HPV is to persist and the greater your risk for developing cancers.

Public places:
It is extremely unlikely that you will pick up HPV from a public shower, sauna, or wet seat. Samples were collected with a toothbrush from the floor and seat surfaces of bathing resorts, showers, swimming pools, saunas, bathrooms and dressing rooms. No HPV DNA-positive samples were found (15).

Risk factors for oral cancers:
You are five times more likely to suffer oral cancer from HPV if you have had more than five oral-sex partners in their lifetime. You increase risk for HPV with
• increasing numbers of sexual partners,
• engaging in casual sex,
• having an early age at first intercourse, and
• using condoms infrequently (16).

Cofactors increase risk for cancer from HPV:
Many things you do increase your risk for cancer and the more risk factors you have, the greater your risk. Avoiding these risk factors after you are diagnosed with a cancer can increase your chance for a cure.

Smoking and being infected with HPV both cause fatal squamous cell cancers of the head and neck. A study from the University of Michigan shows that smokers who have an HPV-linked cancer are six times more likely to have a recurrence than those who have never smoked, and two-thirds of patients with HPV-linked tumors were current or former tobacco users (17). Among those with HPV-linked tumors, six percent of those who never smoked had recurrences, compared to 19 percent of those who had smoked in the past and 35 percent of current smokers. Almost all cases of cervical cancers are caused by HPV, but only one woman of 250 infected with HPV develops cervical cancer. If you are infected with HPV and smoke, you increase your chances of developing cervical cancer 15 times (18).

Lifestyle factors that are associated with increased cancer risk (as well as heart attack risk) include: smoking, taking more than two alcoholic drinks per day, being overweight, not exercising, not eating enough fruits and vegetables, eating too much saturated fat from mammals, eating burnt food (PAHs and HCAs), lack of vitamin D, lack of sunlight, and anything that increases risk for diabetes. Other risk factors include promiscuous behavior that exposes you to hepatitis B and C viruses, HPV, human immunodeficiency virus (HIV), Helicobacter pylori (H. pylori), Human T-cell leukemia/lymphoma virus (HTLV-1), Epstein-Barr virus (EBV), or Human herpes virus 8 (HHV8); working in jobs that expose you to radiation, chemicals such as asbestos, benzene, benzidine, cadmium, nickel, or vinyl chloride, certain metals, pesticides or solvents; taking certain medications and hormones; repeated exposure of your skin to excess sunlight or getting too many X rays.

Treatment of genital warts:
Virtually all genital warts are caused by HPV. Doctors treat genital warts by burning, freezing, lasering, scraping, or removing them surgically. They use chemicals to sensitize skin to sunlight and then use light to burn the warts off. They even peel them off. However, warts often return after all destructive procedures, so I usually recommend
• Fluoro-uracil cream (an anti-cancer drug),
• Imiquimod cream (a chemical that increases your immunity), or
• Diclofenac sodium gel (a drug that blunts your immune reaction).

Treatment for actinic keratoses:
I think that the most effective treatment for actinic keratoses is to use a generic version of imiquimod cream (brand name Aldara). It enhances your immunity so it can more effectively kill HPV. It is applied twice a week for 16 weeks, left on the skin for about eight hours and then washed off.

Current treatment by most dermatologists is to destroy the lesions of actinic keratoses with liquid nitrogen or electrocautery. Surgery is rarely needed. However, once an actinic keratosis becomes a squamous cell carcinoma, surgeons usually remove the entire cancer. A pathologist usually checks the removed tissue to see that there is a 360-degree margin of non-cancerous skin around the removed cancer.

References:
1. New England Journal of Medicine, May 15, 2003
2. Disease Markers, April 2007
3. Expert Review of Dermatology, April 2010
4. Cancer Detection and Prevention, June 2001
5. BMJ. 2010;341:c2986
6. The Lancet, published online March 1, 2011
7. Am J of Ob and Gyn, 2000;183(3): 561-567
8. NEJM, 1998;338(7):423-428
9. Trends in Microbiology, 2011(Jan);19(1):33-39
10. Scand J Infect Dis 1996;28(3):243-6
11. Sexually Transmitted Infections 1999 Oct;75(5):317-9
12. J Med Virol 1998 Nov;56(3):210-6
13. J Clin Microbiol. 1999 Jul;37(7):2270-3
14. Am J Epidemiol 2003 Feb 1;157(3):218-26
15. Rev Med Virol 1999 Jan-Mar;9(1):15-21
16. NEJM May 9, 2007
17. Clinical Cancer Research, February, 2010
18. Cancer Epidemiology, Biomarkers & Prevention, November 2006

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Dear Dr. Mirkin: If calorie restriction prolongs life, won't exercise, which causes you to eat more, shorten life?

Every action that empties full fat cells prolongs life. Nobody has shown that calorie restriction in humans, by itself, prolongs life or is more effective than any other method of emptying full fat cells. Both calorie restriction and exercise empty fat cells.

Full fat cells send out hormones of inflammation that cause cancers, heart attacks, asthma, psoriasis, arthritis, and so forth. Hundreds of articles show that exercise promotes every marker for longevity. It enlarges telomeres, increases size and number of mitochondria and helps to prevents disease. It prevents a high rise in blood sugar, lowers triglycerides and empties fat from both fat and muscle cells. Take your pick. Calorie restriction is very painful.

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Follow-up on hot-weather competition:

In the ezine sent out on May 5, 2011, I debunked low-salt diets for athletes with a story about Tom Osler wining a national 30 kilometer running championship in 103 degree weather in 1967, and claiming that his spectacular win was the result of being on a low-salt diet.

I have known Tom Osler for more than 40 years. I think that he is brilliant. He probably is the slowest runner ever to win two individual national running championships. His fastest mile in high school was slower than five minutes. He won in hot weather because he trained in the heat and was better heat- acclimated than anyone else. He started out slower than everyone else. Then when everyone else self-destructed by going out too fast, he passed them like picking dead flies off a fly strip. Brains win out in the long run.

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Recipe of the Week: Quickest Rice Pudding

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June 5th, 2011
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About the Author: Gabe Mirkin, MD

Sports medicine doctor, fitness guru and long-time radio host Gabe Mirkin, M.D., brings you news and tips for your healthful lifestyle. A practicing physician for more than 50 years and a radio talk show host for 25 years, Dr. Mirkin is a graduate of Harvard University and Baylor University College of Medicine. He is board-certified in four specialties: Sports Medicine, Allergy and Immunology, Pediatrics and Pediatric Immunology. The Dr. Mirkin Show, his call-in show on fitness and health, was syndicated in more than 120 cities. Read More
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