Cervical Cancer and HPV

What a relief that the weather for yesterday’s periodic commute to New York for chemotherapy was much warmer than the bone-chilling, windy backdrop of the past several days. Even more pleasant was a punctual public transportation commute, which got me to my appointment at Memorial Sloan-Kettering Cancer Center (MSKCC) on time. Work on the signals and tracks at NY Penn Station frequently delayed my trains in recent weeks, so I never know quite what to expect these days.

My blood counts were amenable to the scheduled dose of chemotherapy, which was infused as planned. My positive transportation karma continued, and I was back home resting in Pennsylvania by mid-afternoon. No more treatment until after my CT scan later this month for an update on my disease status (queue “scanxiety”).

Traveling alone, I took time during my commute to listen to music on my headphones and catch up on news events. Scrolling through my Twitter feed, I came across the fact that January is Cervical Cancer Awareness Month. It caught my eye, as cervical cancer and oropharyngeal cancer (tongue, throat, and tonsil – as in my particular diagnosis) collectively account for more than two-thirds of the cancer cases caused by high-risk human papillomavirus (HPV) infection. According to the CDC, more than 30,000 new cancers attributable to HPV infection are diagnosed each year.

HPV is the most common sexually transmitted infection in the United States. Nearly 80 million people — about one in four Americans — are currently infected, and about 14 million people become infected with HPV each year. Almost all sexually active people get infected with HPV at some point in their lives.

For most people exposed to HPV, the virus goes away on its own, but a small group of people will experience health problems — sometimes even 20 or 30 years after the initial contact — and go on to develop cancer. In these individuals, HPV can cause changes in the body that can lead to the development of:

  • Cervical, vaginal and vulvar cancer in women;
  • Penile cancer in men; and
  • Oropharyngeal (the tongue, tonsils, and back of the throat), anal, and rectal cancer in both women and men.

The good news is that HPV infections and the seven cancers attributed to them are highly preventable with available vaccines that protect against the high-risk HPV 16 and HPV 18 types responsible for 90 percent of HPV-related cancers. The bad news is that despite reliable data showing the safety and benefits of the vaccines, the rate of vaccination in both sexes is disappointing. Across America, only 49.5 percent of girls and 37.5 percent of boys were up to date with the recommended HPV vaccination series, according to a 2017 CDC report. Interestingly, around 80 percent of adolescents receive two other recommended vaccines—a vaccine to prevent meningococcus, which causes bloodstream infections and meningitis, and the Tdap vaccine to prevent tetanus, diphtheria, and pertussis.

So, with PLENTY of room for progress in vaccinating both girls and boys against HPV, please schedule a time to talk to your pediatrician now to eradicate this cancer-causing virus.

PS – There is undoubtedly a role for gender-specific cancer awareness activities, such as Cervical Cancer Awareness Month. From pink ribbons to professional sports apparel, breast cancer awareness advocates have done a fantastic job spreading the word that October is National Breast Cancer Awareness Month. But each September, during National Prostate Cancer Awareness Month, the color blue doesn’t consume the country with the same vigor. And reduced awareness correlates with less money*, as prostate cancer research receives less than half of the funding as breast cancer research from the American Cancer Society. On this note, perhaps it is time to at least consider “HPV-Related Cancer Awareness Month” or something gender neutral?

* Of course, correlation does not imply causation

No Such Thing as “Risk-Free”

In a recent guest editorial that I penned for BioCentury, I referenced that a parent’s choice whether or not to vaccinate their child against the human papillomavirus (HPV) isn’t a “risk-free” choice. Every drug has risks – consider the following statement by the U.S. Food and Drug Administration (FDA): “although medicines can make you feel better and help you get well, it’s important to know that all medicines, both prescription and over-the-counter, have risks as well as benefits.” I would also point out that there are risks in forgoing a medication.

Let’s take a look at the HPV vaccine’s side-effects according to the prescribing information for Gardasil® 9 (Human Papillomavirus 9-valent Vaccine, Recombinant). The most common side effects include pain, swelling, redness, itching, bruising, bleeding, and a lump where your child got the shot, headache, fever, nausea, dizziness, tiredness, diarrhea, abdominal pain, and sore throat. These are adverse events disclosed by the sponsor (Merck & Co., Inc.) to the FDA from completed clinical trials of Gardasil 9. Since licensure in 2006, over 270 million doses of HPV vaccines have been distributed and the sponsors are obligated to report any new side effects to the FDA.

What’s that you say? You don’t trust the pharmaceutical industry? The Global Advisory Committee on Vaccine Safety (GACVS), an independent expert clinical and scientific advisory body that provides the World Health Organization (WHO) with scientifically rigorous advice on vaccine safety issues of potential global importance, first reviewed the safety data for HPV vaccines in 2007 and subsequently in 2008, 2009, 2013, 2014, 2015, and 2017. In each period, the GACVS examined various vaccine specific safety issues, such as links to Guillain-Barré syndrome (GBS) and other autoimmune safety issues. No other adverse reactions have been identified and GACVS considers HPV vaccines to be extremely safe. According to the WHO, there are now accumulated safety studies that include several million persons and which compare the risks for a wide range of health outcomes in vaccinated and unvaccinated subjects.

Early on, the GACVS was presented with signals related to anaphylaxis and syncope related to the HPV vaccines. According to the GACVS, the risk of anaphylaxis from HPV vaccines has been characterized as less than 2 cases per 1,000,000 doses, and syncope was established as a common anxiety or stress- related reaction to the injection. Anaphylaxis is a severe allergic reaction that needs to be treated right away with an epinephrine (adrenaline) shot. Anaphylaxis is rare, and most people recover from it. Syncope, also known as fainting, is a loss of consciousness and muscle strength characterized by a fast onset, short duration, and spontaneous recovery. It is caused by a decrease in blood flow to the brain, usually from low blood pressure. For these reasons, the prescribing information for Gardasil 9 recommends observation of the individual for 15 minutes after administration.

Next, let’s consider the risks of not getting vaccinated against HPV. Again, according to the prescribing information for Gardasil 9, the vaccine helps protect girls and women ages 9 to 26 against cervical, vaginal, vulvar, and anal cancers and genital warts caused by 9 types of HPV. Gardasil 9 also helps protect boys and men ages 9 to 26 against anal cancer and genital warts caused by those same HPV types. Accordingly, individuals who do not get vaccinated against HPV are at risk for the aforementioned cancers and genital warts.

In addition, the 9 types of HPV that infect the genital areas can also infect the mouth and throat (called oropharyngeal cancers). HPV is thought to cause 70% of oropharyngeal cancers in the United States, with HPV type 16 causing 60% of all oropharyngeal cancers. The HPV vaccine was originally developed to prevent cervical and other less-common genital cancers and has been shown in clinical studies to prevent cervical and other precancers. However, HPV vaccines could also prevent oropharyngeal cancers because the vaccines prevent infection with HPV types that can cause oropharyngeal cancers.

HPV vaccines were not available until I was age 38, which is well-beyond the upper age limit of 26 when the vaccines are considered effective. In late 2015, I was diagnosed with poorly differentiated, oropharyngeal squamous cell carcinoma, HPV type 16 related. My three treatment regimens thus far have included: chemoradiation, immunotherapy and currently chemotherapy.

Side-effects that Michael Becker has experienced from cancer and its treatment (click image to enlarge)

My diagnosis is terminal, so “death” would be the primary side effect from the disease that I would gladly forgo in favor of any of the aforementioned HPV vaccine side effects. Setting my grim humor aside for the moment, there are more than a dozen other side-effects that I have personally experienced to date from either cancer or its treatment (see accompanying image for details). And these side-effects don’t include others that I haven’t personally experienced, such as kidney damage.

I’m an advocate of HPV vaccination and strongly encourage parents to speak with a physician when it comes to deciding whether or not to vaccinate a child. The purpose of this blog post is to underscore that deciding not to vaccinate against HPV isn’t a risk-free decision. In my experience, the diagnosis of any one of the six cancers resulting from HPV infection is associated with plenty of important risks for parents to also consider.

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Help Eradicate Six Cancers Caused by HPV

As a sexually transmitted disease, discussions surrounding human papillomavirus (HPV) can understandably be uncomfortable and/or embarrassing. Interestingly, according to the Centers for Disease Control and Prevention (CDC), HPV is so common that nearly ALL sexually active men and women get the virus at some point in their lives. About 79 million Americans (~25% of the U.S. population) are currently infected with some type of HPV. About 14 million people in the United States become newly infected each year. Accordingly, I thought that a more detailed blog post on the subject was warranted.

HPV is a virus with the ability to infect skin and mucous membranes, or mucosa, that lines various cavities in the body and surrounds internal organs. It can cause normal cells in infected areas to turn abnormal. Most of the time, you cannot see or feel these cell changes. In the majority of cases, the body fights off the HPV infection naturally and infected cells then go back to normal.

There are approximately 179 distinct HPV genotypes, which can be divided into “low risk” and “high risk” groups based on their capacity to drive cancer transformation. Most people with HPV never develop symptoms or health problems; 9 out of 10 HPV infections go away by themselves within two years. Sometimes HPV infections will last longer and can cause certain cancers, warts, and other diseases. There is currently no test to find out a person’s “HPV status.”

The “high risk” HPV subtypes most clearly implicated in cancer are HPV16, 18, 31, 33, 35, 45, 51, 52, and 56, which are capable of causing cancers of the cervix, head and neck, anus, vagina, vulva, and penis. Every year in the United States, HPV causes 30,700 such cancers in men and women.

Most of the time, people get HPV from having vaginal and/or anal sex with an infected partner. In fact, “genital HPV” is the most common sexually transmitted infection (STI) in the U.S.

However, the same types of HPV that infect the genital areas can also infect the mouth and throat. HPV found in the mouth and throat is called “oral HPV.” Only a few studies have looked at how people get oral HPV, and some of these studies show conflicting results. Some studies suggest that oral HPV may be passed on during oral sex (from mouth-to-genital or mouth-to-anus contact) or simply open-mouthed (“French”) kissing, others have not. The likelihood of getting HPV from kissing or having oral sex with someone who has HPV is not known. According to the CDC, more research is needed to understand exactly how people get and give oral HPV infections.

Oral HPV is about three times more common in men than in women. Overall, HPV types 2, 4, 6, 11, 13 and 32 have been associated with benign oral lesions while HPV types 16 and 18 have been associated with malignant lesions, especially in cancers of the tonsils and elsewhere in the oropharynx. The most commonly implicated subtype in oropharyngeal cancer is HPV16, accounting for over 80% of HPV positive cases. Not surprisingly, my initial biopsy results showed that tumor cells were positive for HPV16.

Patients with oral HPV cancer present at a younger age and are less likely to partake in excess alcohol consumption or heavy tobacco use that are associated with corresponding HPV-negative cancers. Additionally, HPV-related tumors more frequently arise in the oropharynx – the part of the throat at the back of the mouth behind the oral cavity. It includes the back third of the tongue, the soft palate, the side and back walls of the throat, and the tonsils (where my cancer started). Smoking-related tumors arise more commonly in the oral cavity, larynx, or hypopharynx.

Oral HPV tumors are more likely to be smaller and poorly differentiated, with a higher incidence of advanced lymph node metastases in comparison to HPV negative tumors. Despite a more aggressive clinical presentation, HPV status is the best independent predictor of survival in these patients.

Signs and symptoms of oral HPV may include persistent sore throat, earaches, hoarseness, enlarged lymph nodes, pain when swallowing, and unexplained weight loss. In my case, the first sign of disease in November 2015 was an enlarged (3-4cm) lymph node on the right side of my neck where the cancer had spread from my right tonsil. Some people have no signs or symptoms.

While there is currently no cure for the virus, there are commercially available prophylactic vaccines against HPV available today: the bivalent (HPV16 and 18) Cervarix®, the tetravalent (HPV6, 11, 16 and 18) Gardasil®, and newer Gardasil 9 (HPV6, 11, 16, 18, 31, 33, 45, 52, 58). Since the HPV subtype 16 was included in each of these vaccines, and this subtype was found in my tumor cells, it is very likely that my cancer could have been prevented had such vaccines been available to me when I was younger.

The HPV vaccine was initially developed to prevent cervical and other less common genital cancers, which raised questions regarding the ability to also prevent oral cancers. In one of the first large studies to explore the possible impact of HPV vaccination on oral HPV infections, researchers found it may confer a high degree of protection. The study of young adults in the U.S. showed that the prevalence of high-risk HPV infection was 88% lower among those who reported getting at least one vaccine dose than among those who were not vaccinated. Researchers reported the results at the recent American Society of Clinical Oncology (ASCO) 2017 annual meeting.

To be an effective preventive strategy, HPV vaccination should start before “sexual puberty.” The CDC recommends routine HPV vaccination for girls and boys at age 11 or 12 (two doses six months apart, a 2016 revision of guidelines that previously recommended three doses). People who get vaccinated later (up to age 26 for young women and up to age 21 for young men) will need three.

The same research reported at ASCO 2017 found that from 2011 through 2014 fewer than 1 in 5 (18.3%) young adults in the U.S. reported receiving at least one dose of the HPV vaccine before age 26. The vaccination rate was much lower among men than women (6.9% vs. 29.2%) at this time.

“The HPV vaccine has the potential to be one of the most significant cancer prevention tools ever developed, and it’s already reducing the world’s burden of cervical cancers,” said ASCO President-Elect Bruce E. Johnson, MD, FASCO. “The hope is that vaccination will also curb rising rates of HPV-related oral and genital cancers, which are hard to treat. This study confirms that the HPV vaccine can prevent oral HPV infections, but we know it only works if it’s used.”

More research is needed to understand exactly how people get and give oral HPV infections that resulted in my oropharyngeal cancer. Recent studies confirm that the HPV vaccine can prevent such oral HPV infections, but only when they are used – and vaccination rates are extremely low. This is disappointing, as vaccination is widely considered one of the greatest medical achievements of modern civilization. Childhood diseases that were commonplace less than a generation ago are now increasingly rare because of vaccines (although the measles are making a comeback since elimination was first documented in the U.S. in 2000). In order to be effective at eliminating communicable diseases, vaccines must be administered to sufficient levels of persons in the community.

If you have a son or daughter, please talk to your doctor about the HPV vaccine. HPV has become a recognized driver of six cancers affecting more than 30,000 people each year, yet there are available vaccines to prevent the majority (about 28,000) of these cases from ever occurring.

 

Sources:

American Cancer Society. Cancer Facts & Figures 2017. Atlanta: American Cancer Society; 2017.

From HPV-positive towards HPV-driven oropharyngeal squamous cell carcinomas. Cancer Treat Rev. 2015 Oct 31.

Centers for Disease Control and Prevention: Human Papillomavirus (HPV) Statistics

J Clin Oncol 35, 2017 (suppl; abstr 6003)