Source: www.medscape.com
Author: Zosia Chustecka
 

Human papillomavirus (HPV) vaccines have now been available for 10 years, but despite many medical professional bodies strongly recommending the vaccine, uptake in the United States remains low.

Data from a national survey show that about 36% of girls and 14% of boys have received the full schedule of HPV vaccines needed to provide protection (Vaccine. 2013;31:1673-1679).

Now the American Society of Clinical Oncology (ASCO) has become involved, and in a position statement issued today the organization calls for aggressive efforts to increase uptake of the HPV vaccines to “protect young people from life-threatening cancers.”

“With safe and effective vaccines readily available, no young person today should have to face the devastating diagnosis of a preventable cancer like cervical cancer. But unless we rapidly increase vaccination rates for boys and girls, many of them will,” ASCO President Julie M. Vose, MD, said in a statement.

“As oncologists, we see the terrible effects of these cancers first hand, and we have to contribute to improving today’s alarmingly low vaccination rates,” she added.

The new policy statement is published online April 11 in the Journal of Clinical Oncology.

The statement notes that HPV vaccination has been previously recommended by many US medical societies, including the American Cancer Society, the American College of Obstetrics and Gynecology Committee, the American Dental Association, the American Head and Neck Society, the American Nurses Association, the American Pharmacists Association, the Association of Immunization Managers, the Society for Adolescent Medicine, and the Society of Gynecologic Oncology.

In addition, a joint letter was sent out to all physicians urging them to give a strong recommendation from the American Academy of Family Physicians, the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, the American College of Physicians, the Centers for Disease Control and Prevention, and the Immunization Action Coalition.

Now oncologists are specifically being asked by their professional body, ASCO, to join in with the push toward greater uptake of the HPV vaccines.

“ASCO believes oncologists can play a vital role in increasing the uptake of HPV vaccines,” the new policy statement says. “Although most oncologists will not be direct providers of these preventive measures, this does not abrogate us from contributing to this process. Our unassailable role in the mission to lessen the burden of cancer…places us in a position of influence. We should use interactions with our patients, primary care colleagues, and health care systems to raise awareness of HPV-related cancers and the role of vaccination in preventing them.”

Oncology providers have a responsibility to serve as community educators.

“Oncology providers have a responsibility to serve as community educators, disseminating evidence-based information to combat misconceptions concerning the safety and effectiveness of the HPV vaccine,” it continues.

“ASCO encourages oncologists to advocate for and actively promote policy change to increase vaccination uptake,” the statement concludes.

Issues With the Statement

However, there are a few issues with the statement, says a prominent researcher in the field of HPV and cervical cancer, Diane Harper MD, professor and chair of the department of Family and Geriatric Medicine, University of Louisville, Kentucky. Dr Harper, who was approached for comment, was involved in early clinical trials with both HPV vaccines (Gardasil, Merck & Co, and Cervarix, GlaxoSmithKline), and has emphasized the need for ongoing screening with Pap tests to prevent cervical cancer.

This is also one of the issues she raises about the ASCO statement, which does not mention screening. “All messages about HPV vaccination must be couched in terms of continued lifetime screening for cervical cancer,” Dr Harper told Medscape Medical News.

The ASCO statement highlights the potential that HPV vaccination has for preventing cancer. (Both vaccines protect against HPV types 16 and 18, and Gardasil offers additional protection against several other types). The statement notes that HPV is the cause of nearly all cervical cancer cases and that HPV genotypes 16 and 18 are responsible for 70% of cervical cancers. In the United States, HPV is responsible for 60% of oropharyngeal cancers, 90% of which are caused by HPV 16. HPV is also the cause of 91% of anal cancers, 75% of vaginal cancers, 69% of vulvar cancers, and 63% of penile cancers, again with HPV 16 as the predominant oncogenic genotype.

However, the statement also notes that “because of the long latency and the prolonged preinvasive phase after infection with HPV, many years of follow-up are needed for the ongoing trials to demonstrate a significant reduction in HPV-related cancers.”

Therefore, intermediate outcomes are being used as surrogate endpoints, it continues. HPV vaccines have been shown to prevent new cancer-causing HPV genotype-specific infections and resultant diseases, such as grades 2 and 3 cervical intraepithelial neoplasias (CIN), vaginal, vulvar, and anal intraepithelial neoplasias (as precursor lesions to cancer).

There is “almost certainty that cancers caused by oncogenic HPV genotypes will be dramatically reduced,” according to the statement.

Dr Harper told Medscape Medical News that the studies conducted to date have shown that “Cervarix has a 93% efficacy against CIN 3 regardless of HPV type; Gardasil has a 47% efficacy against CIN 3 regardless of HPV type, and Gardasil 9 is equivalent to Gardasil in the prevention of CIN 3 disease regardless of HPV type. None of these vaccines can prevent all CIN 3 or potentially all cancers.”

“Hence, the most important take home point is that screening is absolutely necessary as a prevention tool for preventing cancer by early detection of disease that when found, is curable,” Dr Harper emphasized.

Also, Dr Harper noted that the studies ended at prevention of CIN 2/3 disease as a clinical outcome. CIN 3 on average progresses to cancer in 20% of women within 5 years, and to 40% of women in 30 years. But, she points out, “there are no long-term follow-up studies that show that cancers will be averted.”

“The modeling exercises indicate that we have to wait at least 40 years before we will have a detectable decrease in cervical cancers from vaccination, assuming that at least 70% of the population being surveyed is vaccinated,” she added.

In its statement, ASCO cites the success of widespread vaccination against hepatitis B virus in reducing the incidence of liver cirrhosis and liver cancer as “an exemplary health model that supports more widespread HPV vaccination.”

But Dr Harper argues that “the prevention of liver cancer was an unexpected highlight of HBV vaccination. The primary purpose was to relieve the symptoms of chronic HBV sufferers. The continual re-infection with HBV seems to allow a natural infection to act as a booster in this population, which may not be the same for HPV.”

There also remains a question of how long the protection offered by HPV vaccination will last.

The ASCO statement says, “Both vaccines have a known duration of protection of at least 5 years, with ongoing study of the full duration of their effect,” and it notes that “additional research is needed to evaluate duration of protection to determine if booster doses are required.”

Dr Harper said, “Estimates of long-term effectiveness are based on antibody titers, yet there is no surrogate of protection defined by antibody titers.”

She added: “I agree that observational studies will inform the public health authorities about when a booster will be needed and whether it is needed sooner if only 2 doses are received vs later if 3 doses​ are received.”

Last, but not least, there is the issue of safety.

The ASCO statement notes that both Gardasil and Cervarix “reported excellent short- and long-term safety results in clinical trials. The most common adverse effects were mild and included injection site pain (approximately nine in 10 people) and swelling (approximately one in three), fever (approximately one in eight), headache, and fatigue (approximately one in two). These symptoms were transient and resolved spontaneously. The incidence of serious adverse effects was low and was similar to those who received placebo (aluminum-containing placebo or hepatitis A vaccine).”

However, worldwide there continue to be reports of adolescents who report chronic side effects and pain syndromes after being vaccinated against HPV. Some of these have been documented in the medical literature, with physicians reporting instances of previously healthy athletic girls becoming incapacitated with pain, fatigue, and autonomic dysfunction, and some remaining permanently disabled.

The US Food and Drug Administration and the Centers for Disease Control and Prevention have repeatedly said that HPV vaccines have an excellent safety record and that no causal associations have been found with atypical or unusual pain syndromes or autonomic dysfunction. The European authorities have investigated two chronic syndromes reported with HPV vaccination, and have said that there is no evidence to show causation.

However, Danish researchers who were among the first to report these syndromes criticized the investigation and are conducting their own study. There have also been lawsuits filed in several countries, and a class action lawsuit is now planned in Japan against the government and the vaccine manufacturers.

In an interview with Medscape Medical News, lead author on the ASCO statement, Howard H. Bailey, MD, from the University of Wisconsin Carbone Cancer Center, Madison, said that the concerns over safety should not be dismissed and should be studied further.

These issues need to be studied further, even if the authorities say that the vaccines are safe, he emphasized. These reports of girls becoming very ill, having pain syndrome and weakness, should not be diminished, he said, adding: “We can’t just ignore these reports…if there is risk involved, then that needs to be sorted out better.”

However, there is always a possibility that the syndromes and side effects that have been reported “have nothing to do with the vaccine,” Dr Bailey commented, citing the case of now-discredited theory linking autism to the pediatric vaccine for measles, mumps, and rubella.

There may be other explanations for the symptoms that are reported, or it could be that the symptoms/syndrome would have developed in the individual, anyway, but the vaccination precipitated it sooner, he suggested.

Dr Bailey noted that across the United States physicians are very sensitive to the fact that rates of pediatric vaccination have gone down because of the link that had been made to autism, subsequently shown to be false. Even though science eventually showed no link between the vaccine and autism, public confidence in the vaccine was damaged.

“When a person’s life has been devastated by an illness, that is very important, but if it turns out that the illness is not related to the vaccine, and in the meantime, the concerns over safety have stopped thousands of young people from being vaccinated….”well, eventually this will mean that there are more people who die from cancer, he said.

“I would be very reluctant right now to shut down the goals of vaccination over what has been reported, because the bottom line is that we have a tremendous problem with the rising incidence of HPV related cancers including in men as well as women when it comes to oropharyngeal cancers here in the States,” he added.

“The data, at least in my opinion, are so strong that HPV vaccination if it’s done in a [systematic] way will reduce the incidence of these cancers…I don’t want to stop whatever progress we are making when there is at best disagreement over whether these things are associated,” he said, although he also added that “maybe if it was my daughter, I would feel differently.”

Dr Bailey also addressed some of the other issues that had been raised about the ASCO statement, and said he agreed about the importance of screening.

“Even if vaccination does all the things we expect it to do, there is no doubt that cervical cancer screening needs to continue, and that’s a pretty standard recommendation across all of the groups,” he said. “We do not mean to diminish the importance of continued screening,” he said, but he added that screening lies in the domain of other physicians, such as primary care and gynecology, whereas this statement was targeted specifically at oncologists. “To take a step back, we are taking the view of cancer physicians, who take care of women, who are unfortunately too often dying of cervical cancer, and…we wanted to remind people that HPV vaccination can prevent this…as well as other associated cancers,” he said.

“The audience in North America has not been paying attention to this vaccination issue very much,” he continued, and “we wanted to remind oncologists and the public that at the heart of the issue is cancer prevention.

“We have this relatively easy way of preventing cancers over and above the ways that we already use,” he added.

“We wanted to remind people, especially in the oncology community, that there is this intervention out there that we think is highly, highly likely — if applied and used in a population format — will significantly reduce the number of women dying of cervical cancer, the number of men and women dying from oropharyngeal cancer, which is increasing in the US…and that was the main focus of the article,” Dr Bailey commented.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

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