The Slow Journey from HPV Infection to Cervical Cancer

Healthy cervical cells as seen under a microscope. Image: National Cancer Institute

January is Cervical Health Awareness Month. The biggest threat to cervical health is human papillomavirus, or HPV, a virus that is transmitted through a wide variety of sexual activities. If you haven’t yet been sexually active, the best thing you can do to protect cervical health (whether you have a cervix or not) is to be vaccinated against HPV. If you have been sexually active, the vaccine could still be effective, assuming you haven’t already been infected with the strains of HPV against which it protects. And, if you are, or have been, sexually active and have a cervix, it is important to be screened with regular Pap tests (also called Pap smears). When caught in its precancerous stages, cervical cancer can be avoided.

HPV may be tiny, but it packs a punch.

There are more than 100 strains of HPV, approximately 40 of which can be sexually transmitted; of these, 18 strains are thought to cause cancer. Chronic infections by cancer-causing HPV strains, such as HPV-16 and HPV-18 (which together are responsible for 70 percent of cervical cancers), can lead to the development of abnormal cells, which might eventually become cancerous.

In the United States, HPV is the most widespread sexually transmitted disease — 6 million Americans are infected with HPV annually, although most are asymptomatic and unaware they were infected. For most people, the infection clears up within 8 to 13 months, while for others, the infection can lurk undetected. If you are unlucky enough to develop a chronic HPV infection, then you are at increased risk for certain cancers — depending on the site of the infection, HPV can cause cancers of the cervix, anus, and other genitals, as well as the throat.

Low-grade lesions of cervical cells, which can be treated before progressing to cancer. Image: National Cancer Institute

Low-grade lesions of cervical cells, which can be treated before progressing to cancer. Image: National Cancer Institute

Almost all cervical cancers (99 percent) are caused by chronic HPV infection, which is a necessary, but not sufficient, condition for cancer. For a chronic HPV infection to become cancerous, a series of events must take place at the cellular level — environmental factors, such as smoking, can increase the risk for cancer, and some people have genes that make them more vulnerable to HPV infection.

Upon transmission to a host, HPV transmits its DNA into the nuclei of skin cells called basal keratinocytes. The keratinocytes replicate the viral DNA with each cell division, and eventually there are enough virus-filled cells that HPV can be easily transmitted to a sexual partner when skin cells are shed. HPV-infected keratinocytes can also remain within the host, resulting in a chronic infection. At this stage, the viral DNA is permanently integrated with that of the host, which forces the keratinocytes to manufacture viral proteins. These proteins can cause cancer by disrupting the host’s cell cycle.

HPV may be tiny, but it packs a punch. Despite only having a handful of genes, it is able to exploit some of our biological processes at the cellular level. For instance, our bodies are able to attach a “tag” to a protein to mark it for destruction. These tagged proteins, no longer needed or wanted by the body, are broken down into smaller molecules. We also all have proteins called p53, which can suppress the formation of tumors.

Cancer-causing HPV produces a protein that is shaped in such a way that it can physically interlock with both the “tags” that mark a molecule for destruction as well as the tumor-suppressing p53 proteins. When the body sees the tag, it destroys both the viral protein as well as the p53 protein that is attached to it. Our bodies are tricked into destroying our own tumor-suppressing p53 proteins, making us that much more vulnerable to developing tumors.

Just as the above proteins are able to physically fit into and around one another, components of our immune systems work based on the same principle. Our bodies’ defenses produce proteins that attach to the outer shells of viruses, which help us to attack and destroy pathogenic invaders. Our genes affect the shapes of the defensive proteins we produce; some of us might produce proteins that are more easily able to attach to invading HPVs.

Cancerous cervical cells, as seen under a microscope. Image: National Cancer Institute

Cancerous cervical cells, as seen under a microscope. Image: National Cancer Institute

You might have heard of the BRCA mutation, in which certain types of the BRCA gene can make some people more susceptible to breast cancer than others. Researchers have found genes that are similarly involved with HPV infection, such as a gene called HLA-DRB1. If you have a “bad” version of this gene, you will be more susceptible to cervical cancer than people with “good” versions of that gene. A “good” HLA-DRB1 gene codes for a protein that is able to bind to HPV’s viral antigens and present them to the immune system. If a female has a “bad” version of HLA-DRB1 and can’t make proteins that bind to HPV’s viral antigens, her immune system might be unable to stimulate a response to HPV, making her susceptible to HPV infection and ultimately cervical cancer.

This is what we mean when we say an HPV infection is a necessary, but not sufficient, condition for the development of HPV-related cancers. Some people’s immune systems might have a harder time responding to an HPV infection than others, and they will be more likely to develop HPV-related cancer over time. This is why Pap tests are such powerful tools — by catching cellular abnormalities that might eventually turn into invasive cancer, you can be easily treated. Additionally, the HPV vaccine will protect you from the two most high-risk HPV strains.

Planned Parenthood health centers, as well as other clinics and health-care providers, offer both life-saving Pap tests as well as the HPV vaccine. These simple medical interventions are two of the best things you can do to protect cervical health.

11 thoughts on “The Slow Journey from HPV Infection to Cervical Cancer

  1. While I agree that Cervical Cancer is preventable…one should consider why the CDC is recommending the Gardasil vaccination.

    It may actually NOT be the best thing to prevent HPV infection.

    Why? Because Merck pharmaceuticals is now facing a class action lawsuit over the vaccine in Australia, and in September, 2011 it was shown that Merck lied about the vaccine only containing “virus-like” particles. In fact, the vaccines are contaminated with rDNA from the HPV virus.

    People should also remember that on October 25, 2011, an advisory panel to the CDC recommended that the vaccine be administered to boys ages 9 to 26 – creating a whole new market for sales and profits.

    That advisory panel actually receives a ‘kick-back’ on Gardasil sales.

    Moreover, have you ever thought about the actual statistics and why the vaccine is pushed so hard…and why everyone and their neighbor says HPV is such a huge health issue?

    Remember, the CDC itself says that 90% of people infected with HPV clear the virus from their system within 2 years.

    There are an estimated 307,006,550 people in the United States. Let’s divide this number by 2, which will give us the 50% of people who could acquire an HPV infection sometime during their lives.

    That leaves us with 153,503,275 people that will likely be infected with HPV.

    So, let’s divide 153,503,275 by 2 assuming that of this number, half are women.

    This leaves us with 76,751,637.

    Of those, only 12,000 will be diagnosed with cervical cancer caused by HPV, and of those, 4,000 will die.

    That’s 0.02% (rounded up) diagnosed with cervical cancer. Of that number, 33.3% will die.

    That’s 0.005% of the numbers of HPV infected women in America.

    Obviously, just one person dying is too many. However, you can see from the numbers that HPV caused cervical cancer deaths are extremely low.

    It’s obvious that at $150 per shot (and it takes 3 shots to be vaccinated) Merck & Co., Inc. are going to make a killing if ALL girls are vaccinated.

    Their motivation is obvious.

    • * Your claim about Gardasil being contaminated with viral DNA is patently false. The person who made that claim didn’t share his methods with the scientific community for peer review. The way the vaccine is made, it is impossible for viral DNA to turn up in the vaccine. The only HPV gene used in manufacture is the L1 gene, which codes only for the noninfectious protein shell.

      * Cervical cancer rates are astronomical in countries without widespread access to Pap testing. The vaccine would be especially life-saving in those populations. It doesn’t matter if “most” people clear the virus, because when we’re talking about hundreds of millions of people, a small percentage adds up to a lot of lives. Even if we only take into account countries with widespread access to Pap tests, as you seem to be doing, the vaccine at the very least will decrease the amount of precancerous lesions that must be treated. It will take a decade or more to see how much cervical cancer rates decrease.

      * It will be interesting to see if the costs of the vaccine are offset by the money saved in treating precancerous lesions. We spend millions of dollars a year on treatment.

      * The Big Pharma conspiracy theories don’t fly with me in the case of vaccines. Treating the diseases prevented by vaccines is a MUCH bigger money maker than vaccination.

      We have a post about HPV vaccine myths scheduled for next Tuesday, and it addresses most of your claims in more detail. You’re invited to read it and check out the supporting evidence, which is linked to.

      ETA: Now that I’ve done some light detective work, I am interested to see that you’ve been busy today posting this identical comment to a number of blogs, under the names “Simon” and “Will,” and that you’re affiliated with a supplement company that has been issued warning letters by the FDA for falsely advertising that its product can prevent, treat, or cure human disease without competent and reliable scientific evidence. We’ve addressed bogus STI cures on this blog before, and funnily enough, the company you’ve worked with was included on the list of fraudulent companies referred to in our post.

    • It is really expensive! I don’t know what country you live in, but in the United States there is a VFC (vaccines for children) program, and Merck has a vaccine assistance program for uninsured people. Here’s to hoping it will come down in price as they recoup their R&D costs.

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