The Connection Between HPV and Cancer

By Diane M Harper, MD, MPH, MS Professor of Medicine Center of Excellence for Women's Health Departments of Obstetrics and Gynecology, Community and Family Medicine and Biomedical and Health Informatics University of Missouri-Kansas City School of Medicine

The Connection Between HPV and Cancer

What is HPV?

HPV stands for human papillomavirus. There are animal papillomaviruses too, but they cannot infect humans. 

HPV is a large family composed of species (groups) and then types. For instance, there are two major species that contain the 15 types of HPV that cause cancer. One species contains HPV 18 and 45, the most common causes of glandular cancers; the other species contains HPV 16, 31, 33, 51, 52, 58, the most common causes of squamous cancers. Most of the cancers are related to HPV 16 because HPV 16 is the quickest to progress into a cancer, but the other types, given enough time, can also form cancers. 

There is another species that contains 6 types associated with genital warts including HPV 6, 11, 13, 44, 55, and 74. These types do not cause cancer.

When HPV invades the skin cell and stays separate from your human DNA, it can change cells into warts and abnormal areas that are not cancer pre-cursors, and it can reproduce making more viruses to infect you or others. 

When HPV invades the skin cell and inserts itself into your human DNA to become part of your human DNA, it can no longer reproduce and make more viruses, but it can set off the genes to start the cancer process.

How does one get HPV? Do I have to have sex to get HPV? What about oral sex?

HPV is a human skin-to-human skin contact infection. Not fluids, not blood, not saliva, not sperm. HPV that causes hand and feet warts are very different types than the types that cause genital warts or cancer. A hand wart will not give you genital warts.

HPV types that cause cancer live in moist, generally dark, places, such as in the soft tissue under your fingernails, and the genitals, anus and mouth. For men who are not circumcised, under the foreskin is the most likely place of infection and cancer. But the penile shaft and the scrotum can be HPV-infected as well. For women, the vulva or outside genital skin, including the labia (lips), can be infected with HPV types that cause cancer.

This skin-to-skin contact can lead to anal cancer.  Anal cancer from HPV does not require that you have anal sex, though. Any genital HPV infection puts you at higher risk for anal HPV infection. The group at highest risk for anal cancer is the group of men who have sex with men.

This skin-to-skin contact can also lead to oral cancer. Three times as many men have oral cancer as women, making men at highest risk for HPV-associated oral (head and neck) cancers.

All ages of females are infected with high-risk HPV. Most often, infection happens because of penetrative sexual intercourse, but any kind of skin-to-skin contact may lead to infection. The skin-to-skin contact does not have to be related to sexual activity. 

While younger children are less likely to be infected with HPV, 10-15% of our young children already have cancer-causing HPV infections.  There is no one age at which all females are free from HPV infection.


Can I get tested for HPV? I heard there was an HPV DNA test. Is it more effective?

HPV is detected by scraping off the top layer of skin cells that cover the cervix, by busting open the cells and seeing if the high-risk HPV DNA is present. 

Because over a third of women less than 30 years of age will have a HPV infection, we do not test women less than 30 years of age for high-risk cancer-causing HPV types – too many women would come up as positive.

The Pap test is very effective at detecting most pre-cancerous changes of the cervix.  By adding the HPV test for high-risk cancer-causing types to the Pap test, a small number of women whose pre-cancerous changes could not be detected by Pap alone can be detected. But, when we add HPV testing to find what a Pap test alone did not find, we find a whole bunch of women who are HPV-positive but who do not have pre-cancerous changes. So, there is a penalty of over-diagnosis when we use both tests together.

If one or more of these tests is positive, you still need to follow up with your doctor, but don’t be surprised if he/she tells you that you have an infection that is likely to go away on its own. Of those infected with HPV, 50% of them will fortunately clear the virus within 8 months, 90% of them within 2 years.

How does a Pap smear test for HPV? If the test is negative does that mean I'm safe?

Pap testing looks at the shape of the cell nucleus compared to the whole skin cell from your cervix. If HPV has caused any damage to the cell, we can see the changes in the shape of the cell.

HPV that lives inside the cell that is not causing any damage to the cell will NOT be seen as an abnormal cell on a Pap test because the virus has not caused any changes, but might be detected on the HPV test.

Pap testing has been used as a single test alone to detect early pre-cancers and is very effective. If you do not have access to HPV testing or cannot afford it, Pap testing alone is still a very good test to use for your screening.

If your HPV test and your Pap test are both negative and normal, your chances for having a cervical cancer precursor are less than five in 1,000 — very low.

How often should I get Pap smears to test for cancer?

In the US, the recommendations for Pap testing include starting at the age of 21 years and repeating it every 3 years, if it is normal.

At the age of 30 years, you have the option of having both the Pap and HPV test, or having just the Pap test. If you choose the Pap test alone, and it is normal, you need to continue with the Pap test every 3 years. 

If you choose the Pap and HPV test, and both are normal/negative, then you should be screened every 5 years, and not any earlier.

At the age of 65 or 70 years, a woman, in discussion with her doctor, can decide if she can stop her Pap and HPV testing. If a woman has had a hysterectomy and never had an abnormal Pap test, then she no longer needs to have Pap testing.

How is HPV treated?

There is no medicine or cure for HPV.  We treat cells that have changed because of the HPV infection with freezing or excision. This treatment removes the dangerous tissue, but does not cure you of HPV.

Does the virus go away? Or am I stuck with it like with herpes or HIV?

HPV is not like HIV or HSV or Hepatitis B, the other viruses associated with sexual activity.  HPV is not transmitted by blood, by semen, by fluids, by saliva, or by secretions. Getting a natural HPV infection will not produce lasting immunity; hence, you can get this same type of HPV infection over and over again. 

It is a virus that is almost undetected by the body, and 90% of the time HPV never does anything bad to the human body. Only in 5% of infections do precancerous changes happen.

Genital warts are much more rare than infections with cancer-causing HPV types. For every one person with genital warts, there are 25 women with abnormal Pap tests due to HPV infections. 

What are the best ways to prevent getting HPV?

Be choosy about your sexual partners. The more partners you have, the more likely you will get HPV.  Condoms can prevent some HPV infections, but condoms do not prevent all infections. Condoms only cover one part of skin (the penis) that could be exposed to or transmitting HPV.

What cancers does it cause? Does it really cause 1 out of 20 cancers?

Eighty-eight percent of all HPV-associated cancers are cervix cancer, by far the most common cancer from HPV infection. The next most common type of HPV associated cancer is anal cancer, followed by oral, penile and vaginal cancers. 

Considering the whole world, HPV causes 1 in 20 cancers. In developed countries like the US, HPV causes 1 in 50 cancers, but in developing countries like Guatemala, HPV causes 1 in 15 cancers. 

Should I get the vaccine? How does it work?

First of all, there are two HPV vaccines: Gardasil and Cervarix. Gardasil protects against HPV 6 and 11, which cause genital warts. It also protects against HPV 16 and 18, the two most common cancer-causing types. Gardasil is proven to work for at least 5 years only if all three doses are taken on time.

Cervarix protects against seven high-risk HPV types: HPV 16, 18, 31, 33, 45, 51, 52 and has cross protection shown to prevent 30% of genital warts. Cervarix is proven to work for at least 9.4 years, and still works if only one dose (for 4 years) or two doses are received. 

Both vaccines can only prevent infection with HPV. If you already have the infection, the vaccine will not remove the infection. Likewise, the vaccine will not make the infection progress to a pre-cancer.

If the vaccine wears off too soon, then you have no protection against new infections.

Neither vaccine can protect against all the high-risk cancer-causing types. Therefore, you must continue to get Pap testing.

The HPV vaccines are an option, not a necessity, to help you maintain a healthy cervix. You must personally weigh the benefits and risks of vaccination for your health.

Is that vaccine dangerous?

Gardasil and Cervarix will cause redness, pain or swelling in about three-quarters of those who get the shot. Some who get the vaccines become light-headed and dizzy. They should stay seated for 15 minutes after the shot to make sure that any dizziness goes away before they stand up.

Everything we give in medicine has the potential for harm.  Among the millions of females vaccinated, Gardasil is associated with over 3000 severe adverse events reported to the CDC in the Vaccine Adverse Events Reporting System. When a side effect occurs at a rate of less than 1 in 10,000, the CDC declares it “very rare” and it is not considered a public health risk. The small number of severe side effects falls in this very rare category. Whether you are willing to risk this harm is a personal decision, given that Pap testing is the required screening for cervical cancer.

Why are these vaccines not available for those above the age of 26?

Gardasil has been tested in women 26-45 years of age; Cervarix has been tested in women 25-72 years of age. Both provide protection from specific HPV type infections in those women who have never been exposed to those types of HPV before.  Because the numbers of women over 26 years who have not been exposed to HPV are small, the public health benefit of vaccination is not recognized. But you personally may benefit if your past sexual exposure has been limited. This is something to discuss with your doctor.

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