Your Weekly Checkup: The Importance of Immunization

“Your Weekly Checkup” is our online column by Dr. Douglas Zipes, an internationally acclaimed cardiologist, professor, author, inventor, and authority on pacing and electrophysiology. Dr. Zipes is also a contributor to The Saturday Evening Post print magazine. Subscribe to receive thoughtful articles, new fiction, health and wellness advice, and gems from our archive. 

Order Dr. Zipes’ new book, Damn the Naysayers: A Doctor’s Memoir.

I have written previously about the need to get an annual flu shot (my wife and I got ours two weeks ago), human papilloma virus, shingles, and other types of vaccinations, but that “trust in vaccinations appears to be declining, especially in small pockets of people living in insular communities. This puts under-vaccinated children at risk for contracting preventable diseases.”

I also noted that “vaccination, along with the discovery of antibiotics, is one of the major public health success stories in the history of medicine. Despite this, the incidence of vaccine-preventable diseases such as whooping cough and measles, after falling to all-time lows, has begun to increase.”

The potential consequences expressed in those statements are becoming apparent. Recent data from the Centers for Disease Control and Prevention published in the Morbidity and Mortality Weekly Report show that 1.3 percent of children born in 2017 did not receive any vaccinations. This represents a four-fold increase from 0.3 percent in 2001.

The Advisory Committee on Immunization Practices recommends routine vaccination against multiple potentially serious illnesses, including hepatitis A and B, rotavirus, diphtheria/tetanus/ pertussis, influenza, pneumococcus, polio, measles/mumps/rubella, varicella, meningococcus, and HPV.

However, the falling vaccination rate means that an estimated 100,000 young children have not been vaccinated against any of these diseases. Children in rural areas and those without insurance have higher rates of not being vaccinated.

While these results are sobering, recent overall vaccination coverage among young children remains high, and most children are routinely vaccinated.

Since the number of children who have received no vaccinations by age 24 months has been gradually increasing, the results highlight areas for improvement, such as educating parents who refuse to let their children become vaccinated and creating vaccination opportunities for rural populations and the uninsured. It is important to stress that most of the vaccines require more than one dose, with many of those multiple doses administered in the first year of life. We need to place greater emphasis on those vaccines that require booster doses.

The increasing percentage of unvaccinated children raise concerns about potential pockets of susceptibility where children are not well protected. For example, measles was declared eliminated from the United States in 2000, yet outbreaks caused by imported cases continue to occur each year; 118 measles cases were reported in 2017. The continued occurrence of measles outbreaks in the United States underscores the need to ensure high vaccination coverage among all young children.

Vaccines work not only by inoculating individuals from contracting a disease but also by creating herd immunity. When more than 80% to 90% of a population is vaccinated, chains of infection are likely to be disrupted, stopping or slowing the spread of disease, which protects those few not vaccinated. Therefore, not immunizing the few can affect the many.

Reduced vaccination rates around the world can cause outbreaks among Americans, as under-vaccinated Americans may become infected while visiting places with weaker herd immunity and carry the virus or bacteria back to the states. International travel also provides the opportunity for infected individuals to come in contact with susceptible Americans.

We can do better. Preventing disease is far preferable (and cheaper) than having to treat it after it occurs.

Be smart. Prevent disease with appropriate immunizations — in your children and in yourself. The minimal risks and expense are far less than contracting and treating the disease.

Your Weekly Checkup: The Controversy Around the HPV Vaccine

“Your Weekly Checkup” is our online column by Dr. Douglas Zipes, an internationally acclaimed cardiologist, professor, author, inventor, and authority on pacing and electrophysiology. Dr. Zipes is also a contributor to The Saturday Evening Post print magazine. Subscribe to receive thoughtful articles, new fiction, health and wellness advice, and gems from our archive. 

Order Dr. Zipes’ new book, Damn the Naysayers: A Doctor’s Memoir.

Two weeks ago I wrote about the need for vaccinations to prevent common infections with viruses such as measles, mumps and whooping cough. I didn’t have space to discuss vaccination against a highly important and more controversial infection: the human papillomavirus (HPV). More than 200 related HPV viruses exist, with about 40 having potential transmission through sexual contact.

HPV infection remains one of the most common sexually transmitted diseases in both males and females. Many infections do not cause symptoms, and nine out of ten disappear spontaneously in two years. However, HPV types 16 and 18 have been implicated in causing cancers and HPV 6 and 11 in causing warts. Worldwide, HPV infection is responsible for half a million cases of cancer and more than a quarter of a million deaths every year, with the highest incidence in developing countries lacking resources to promote prevention or provide treatment. Nearly 80 million Americans (about one in four) are infected with HPV, with over 6.2 million new cases annually. HPV causes 32,500 cancers in American men and women each year. HPV vaccination can prevent about 30,000 from ever developing.

Effective HPV vaccines have been available for almost a decade. More than one hundred countries have adopted vaccine programs for females, and many are extending the indications to include males. However, widespread adoption of vaccination remains controversial.

While state-mandated immunization programs have increased the number of children vaccinated, many state legislatures do not require universal HPV vaccination. Objections include the concern that the vaccine might encourage sexual contact at earlier ages or promote higher risk sexual practices. To me, the argument that the vaccine will prevent sexually related cancers appears far more persuasive.

The Centers for Disease Control and Prevention (CDC), together with other professional associations, recommends that children 11 or 12 years old get two shots of HPV vaccine six to twelve months apart. In general, HPV vaccine is recommended for young women through age 26, and young men through age 21. The overwhelming evidence favors administration of the vaccine to prevent the precancerous and malignant disease conditions caused by HPV infection. The risks of the vaccine are within the range of complications noted with other vaccination programs and should not prevent vaccine administration. Parents and health care workers need to be educated that the benefits of HPV vaccination far outweigh any risks.

The Post Investigates: Cancer Vaccines

Cancer researcher Patrick Hwu, M.D., likes to think of the body’s immune system as the armed forces in charge of homeland defense and of tumor cells as homegrown terrorists. When everything is going well, the immune system recognizes malignant cells and destroys them. But like a general whose troops are not quite the crack soldiers he expected, Dr. Hwu has to admit, the terrorists too often get the better of his wimpy forces, which is why 560,000 Americans will die of cancer in 2009, the American Cancer Society forecasts. “We don’t really know why the immune system doesn’t keep most cancers in check,” says Dr. Hwu, a cancer immunologist at the M.D. Anderson Cancer Center in Houston. “The tumor might disguise itself from the immune system or make things that suppress the immune system.”

When he was working at the National Cancer Institute (NCI) in the 1990s, Dr. Hwu and colleagues decided they needed an innovative way to retrain the immune system. What if they could inject into cancer patients the very “markers” that stud the surface of malignant cells? That’s how vaccines for infectious diseases such as measles and smallpox work, by training the immune system to recognize and attack the markers on disease-causing viruses. In this case, Dr. Hwu and others reasoned that injecting “tumor antigens” might train the immune system to recognize the tumor cells as foreign and destroy them. It would be a “cancer vaccine” — not a vaccine like that for measles, which prevents a disease, but one that treats it. (These cutting-edge cancer vaccines are not to be confused with Gardasil, a vaccine that primes the immune system to attack the virus that causes cervical cancer. Very few human cancers are known to be caused by viruses, so “cancer vaccine” has come to mean one that treats existing cancer.)

The NCI scientists were hardly alone in dreaming of a cancer vaccine. The appeal was obvious: Oncologists’ cancer-fighting arsenal consisted of surgery, radiation, and chemotherapy — or as critics like to say, cutting, burning, and poisoning. Not only did the three weapons come with serious side effects, but they were far from universally effective. Perhaps harnessing the immune system would vanquish tumor cells with little to no collateral damage to the rest of the body. The idea took hold in a serious way in the 1970s, recalls Dr. Len Lichtenfeld of the American Cancer Society, “and it was going to be a slam dunk. We were going to cure cancer.” Obviously, that did not happen. Instead, vaccine after vaccine failed. But with advances in their understanding of both cancer and immunology, scientists finally scored some notable successes: Three large-scale studies, called Phase III clinical trials, presented at the 2009 meeting of the American Society of Clinical Oncology (ASCO), suggest that cancer vaccines may one day play a role in cancer treatment.

Vaccine Renews Hope Dr. Patrick Hwu meets with Hilde Stapleton, who credits the trial vaccine plus interleukin-2 with knocking her melanoma into remission. In May 1999, Stapleton found a suspicious mole behind her left knee. After surgery to remove the mole and lymph nodes (the cancer had spread) at M.D. Anderson, she enrolled in an early cancer vaccine study. But by 2006, the melanoma had returned. Because the cancer had metastasized to her lungs, her earlier experience in a vaccine trial led her to volunteer for Hwu's trial the following spring. She has been in full remission ever since. "I'm, pleased with the results," she says. Image: © AP Photo/David J. Phillip.
Vaccine Renews Hope—Dr. Patrick Hwu meets with Hilde Stapleton, who credits the trial vaccine plus interleukin-2 with knocking her melanoma into remission. In May 1999, Stapleton found a suspicious mole behind her left knee. After surgery to remove the mole and lymph nodes (the cancer had spread) at M.D. Anderson, she enrolled in an early cancer vaccine study. But by 2006, the melanoma had returned. Because the cancer had metastasized to her lungs, her earlier experience in a vaccine trial led her to volunteer for Hwu's trial the following spring. She has been in full remission ever since. "I'm, pleased with the results," she says. Image: © AP Photo/David J. Phillip.

In one study, a vaccine based on the work of Dr. Hwu and his NCI colleagues extended what’s called progression-free survival — how long patients live before a cancer that has been treated with chemotherapy or radiation returns — in people with advanced melanoma, one of the most lethal cancers. The vaccine consists of antigens that stud melanoma cells. By injecting these “gp100” molecules into patients, “the vaccine activates the T cells of the immune system to recognize the antigens on the surface of the tumor,” says Dr. Hwu. “The T cells then secrete enzymes that poke holes in the tumor cells’ membrane, causing it to disintegrate” and the cancer cells to die.

This was the first time a melanoma vaccine had shown any benefit in a Phase III trial, but even with this distinction, it was no “slam dunk.” The 93 patients who received a standard therapy called interleukin-2 and no vaccine remained in remission for an average of 1.6 months. The 86 patients who received the vaccine plus interleukin-2 remained in remission for just under three months; hardly a big improvement. And on what every cancer patient cares about most — staying alive — the vaccine fell short. Vaccinated patients lived 17.6 months, on average, while unvaccinated patients lived 12.8 months, a difference that statistical analysis determined could be due to chance.

Why wasn’t the benefit greater? It’s possible that the patients did not have enough T cells to mount an effective immune response, says Dr. Hwu. Or maybe, for some reason, the T cells do not find the melanoma cells. Perhaps the tumor disguised itself, hiding the antigen that the T cells were trained to look for. “It’s possible that we did not have enough soldiers, or that they were not well-enough trained, or that they were not able to find the battlefield,” says Dr. Hwu. It’s also possible that a vaccine needs to contain more than the gp100 antigen. “Unique antigens specific to a patient’s cancer do exist, and using them might stimulate a more effective immune response,” he says. “But it would take months to synthesize such a custom-made vaccine,” and advanced melanoma patients do not have months.

Another study unveiled at ASCO this year, however, took the customization approach. Invented by M.D. Anderson’s Larry Kwak when he, too, was at NCI, the vaccine contains markers from each patient’s cancer — in this case, a form of non-Hodgkin’s lymphoma called follicular lymphoma, which is a cancer of (ironically) immune-system cells called B cells. After a biopsy harvests a patient’s malignant B cells from the lymph nodes, it takes about one month to make the vaccine. “The vaccine uniquely recruits the patient’s immune system to seek and destroy only tumor B cells,” said Stephen Schuster of the University of Pennsylvania, who led the study.
“It’s the ultimate in personalized therapy,” adds Dr. Kwak. “Even if patients have the same type of lymphoma, the tumors will still have different antigens, and that’s what you want your vaccine to contain.” The 76 patients who received the custom-made vaccine after a standard course of chemo remained disease-free just over one year longer than the 41 patients who received the chemo alone (44.2 months compared to 30.6 months). In an earlier Phase II study at NCI, patients have remained disease-free for an average of eight years.

Crucially, all the patients in the latest study were in complete remission or had no detectable cancer when they received their personalized vaccine. That is, they had responded to standard chemo and sustained a remission for six months. To skeptics, that raises the possibility that these patients’ cancer might have been less aggressive, and that fact — not the vaccine — accounts for their longer survival. In addition, the vaccine was compared to chemo that has now been superseded by something more effective. Oncologist Ron Levy of Stanford University, a founding father of cancer vaccines, gives BioVax ID “a qualified yes” in terms of effectiveness, but only a “maybe” on whether it will find a meaningful role in treating patients with follicular lymphoma.

Dr. Larry Kwak from M.D, Anderson are working on "personalized" vaccines that prime the immune system to go after a unique biological tag found only on tumor cells.<br />Photo © Wyatt McSpadden Photography
Dr. Larry Kwak from M.D, Anderson are working on "personalized" vaccines that prime the immune system to go after a unique biological tag found only on tumor cells. Photo © Wyatt McSpadden Photography.

Dr. Kwak sees it differently. He admits that the vaccine — and possibly all cancer vaccines — work best in patients whose tumor has shrunk to almost nothing or who are in complete remission. “Then you bring in the vaccine to mop up any remaining cancer cells,” he says. “That’s the strategy, and it should work for other cancers.” If he’s right, then the failures of other cancer vaccines might be because the patients in those studies had active and sometimes widespread cancer. “We now suspect that cancer vaccines will not work very well against advanced tumors,” says Dr. Kwak. “Tumors have the ability to turn off the immune response, and the more tumor you have, the more factors that can do that.”

That may explain why a vaccine for prostate cancer has fallen short. Called Provenge, it failed to beat back disease, let alone improve survival, in early tests, and the Food and Drug Administration refused to approve it in 2007. But the manufacturer, Dendreon, has spent an estimated $560 million on it and isn’t giving up. In a new trial, also presented at ASCO this year, the company announced that among men whose prostate cancer was no longer responding to hormone treatment or chemo, those who received Provenge lived four months longer than those who did not, 26 months versus 22 months. Just under one-third of the Provenge men were still alive after three years, compared to just under one-quarter of the men who did not receive the vaccine — 31 percent versus 23 percent. That’s far from a cure, but Dendreon is hopeful that it will get a green light from the FDA in 2010.

But don’t expect that to open the floodgates for cancer vaccines. So many have failed that it seemed as if they were going to be yet another therapy that looked terrific on paper, and even in lab animals, but which crashed and burned when tested in people. For instance, in 2006 a pancreatic-cancer vaccine called PANVAC-VF failed to improve overall survival. Considering that it was being compared to chemotherapy that keeps patients alive for a median three months, the result was a big disappointment.

The encouraging results for the melanoma and follicular lymphoma vaccines — and, to a lesser extent, for Provenge — have definitely been heard, breathing new life into a field that had been hanging by a thread. “Looking to the future, I think we’ll see a role for vaccines where the cancer is found very early, when the disease burden is small [because the patient is in remission], or when there are circulating cancer cells that can’t be eliminated any other way,” says Dr. Lichtenfeld. “But it looks unlikely that cancer vaccines will produce a response in people who have cancer throughout their system.” The latter, of course, are the sickest of the sick, so there is no small irony in the likelihood that this most innovative of cancer treatments will help not those who need it most, but those with an already hopeful prognosis.