HPV: To vaccinate or not to vaccinate

After some alarming side effects were reported abroad, Health Ministry officials decided to think again about giving schoolgirls shots against human papilloma virus.

By JUDY SIEGEL-ITZKOVICH
PROF. UZI BELLER 370 (photo credit: Judy Siegel-Itzkovich)
PROF. UZI BELLER 370
(photo credit: Judy Siegel-Itzkovich)
Although vaccinations can take much credit over the past century for drastically reducing child mortality and doubling life expectancy, immunizations remain controversial among the general public and even among physicians. Just look at opposition from some parents to immunizing their children against the polio recently detected in Israeli sewage systems.
The vaccination against human papilloma virus (HPV) – which German virologist Prof. (emeritus) Harald zur Hausen discovered in cervical cancer biopsies and for which he received the Nobel Prize in Physiology or Medicine in 2008 – is also controversial, even though over 50 countries around the world already vaccinate girls (and some even boys) to prevent the sexually transmitted virus from, perhaps, causing cervical cancer, as well as precancerous lesions and genital warts.
There are two brands of vaccine.
Cervarix is manufactured by Glaxo- SmithKline to prevent infection from the type 16 and type 18 of HPV that are said to cause about 70 percent of all cervical cancer cases.
In addition to types 16 and 18, the Merck & Company’s Gardasil also targets type 6 and type 11, which cause about 90% of genital warts cases. Injected into the muscle of the upper arm in a series of three shots over a period of six months, neither contain live virus, so the vaccines cannot infect the patient.
More than 150 million doses of the two vaccines have been administered around the world (most to teenage girls but in some countries even to some boys so they do not infect their sexual partners) in over 50 countries. Since the vaccines became available around six years ago, the Health Ministry in Jerusalem discussed the possibility of adding HPV vaccine to the schedule of vaccine provided at government expense, but many argued it was too expensive and that the number of cervical cancer cases among Israeli women was too low to justify the expense.
Male circumcision of Jews and Muslims was given as a major reason for the lower rate, along with conservative sexual practices among traditional populations. But as no one has documented sexual behavior among religious men and women – within or outside marriage – the real risk is unknown.
The cost of privately purchasing the vaccine privately is still high – around NIS 660 per shot in the Superpharm chain or half price for those with supplementary health insurance – but the Health Ministry says it is able to buy the vaccine in large quantities much more cheaply; it signed a deal to purchase the vaccine for just NIS 70 per shot.
However, public health experts believe that given the sexual connotations of the vaccine, it may be that haredi (ultra-Orthodox) schools will allow their pupils to get the shots, and modern Orthodox parents in the state religious school system may also be reluctant.
The ministry had initially decided to begin free vaccination of all 65,000 14-year-old girls in school this fall, but there were second thoughts after Dr. Chris Shaw, researcher at the University of British Columbia, and UBC postdoctoral biochemist Lucija Tomljenovic (now doing research in Israel) claimed that there were “serious health concerns” regarding the side effects of the HPV vaccines.
“Most people who get these vaccines are fine... but some people may get sick... so claiming that there are no adverse reactions aside from a sore arm is not strictly true,” the Vancouver researchers insisted in a published journal paper.
Among the claimed side effects were rare cases of inflammation of central nervous system blood vessels in two young women who died after being vaccinated with Gardasil; no lab findings in autopsies, however, could explain their deaths. Other reported non-fatal side effects were lupus-like symptoms, other autoimmune diseases and premature ovarian failure.
Criticized regarding its original decision to vaccinate girls with Cervarix, which is somewhat cheaper than Gardasil, even though the latter offers more protection, the ministry decided that during the first year it would use Cervarix and in the second year Gardisil, the price of which has come down. But that would mean that girls of different ages would be protected against difference types of the virus.
HEALTH MINISTRY director-general Prof. Ronni Gamzu convened a meeting in Tel Aviv 10 days ago of 40 leading experts on gynecology, oncology, women’s health, vaccines and other specialties who discussed the pros and cons of the HPV vaccine.
Hearing the various sides, Gamzu declared at the end that he would consider the issue and decide whether the vaccination of school pupils would go ahead or not.
In the heated discussion, Shaare Zedek Medical Center’s obstetrics/gynecology chief Prof.
Uzi Beller was the main voice urging caution, while the vast majority of those present endorsed the launching of the school vaccination program. Beller, in an interview with The Jerusalem Post in his office, noted that the two pharmaceutical companies that manufacture the vaccine have been extremely aggressive in their lobbying and marketing; the vaccines are worth billons of dollars to them. At the same time, he said, many medical professionals who advocate vaccination have been pushing a “populistic campaign without being familiar with the issue.”
Beller, an international authority on gynecological cancers who treats patients on a daily basis, can hardly be accused of being apathetic regarding the plight of women who contract cervical cancer. “I would be happy to see a solution to this disease,” said the gynecologist. “I am not at all against vaccines. I just underwent the oral polio vaccination as the Health Ministry instructed medical institutions to give the two drops to every doctor who is in direct contact with patients.
“But HPV is different from all other vaccines. It is not a vaccination against cervical cancer but against a virus that in some cases causes a premalignant condition, and in a small number of cases, a malignancy. In a year in Israel, there are 180 cases of cervical cancer, and half [of those with the disease] die of it. [This] is a rate of five per 100,000 residents – the lowest rate of cervical cancer in the world.”
One would have thus have to vaccinate 20,000 girls to prevent one case, he said, although he added that “if the vaccine prevented cervical cancer, I would be in favor. The vaccine [was hailed] in 2003 as being ‘the beginning of the end for cervical cancer,’ but it was exaggerated.”
Widespread application of the Pap test has reduced cervical cancer rates in developing countries by nearly 80% over the past five years. Named for its developer, Greek physician Georgios Papanikolao, the test involves using a speculum to open the vaginal canal and collect cells from the outer opening of the cervix. The cells are then examined under a microscope for abnormalities indicating pre-cancerous changes usually caused by sexually transmitted human papillomaviruses.
But, as the two vaccines do not provide protection against all HPV types, sexually active women are advised to undergo periodic Pap smears for screening.
“Unlike mammography, there is no organized health fund screening for cervical cancer required, even though Pap smear testing has been shown to be worthwhile in early detection. I want to see fundamental studies proving efficacy, and they do not exist. The vaccines,” Beller said, “were tested on mostly white women attending colleges and university – mostly from developed countries and healthy. The data were based on a relatively shortterm follow-up period. What is known does not yet justify widespread vaccination of healthy girls.”
Beller stressed that girls taking the vaccine should continue with Pap screening. “All the experts accept this, and This is accepted by everybody and actually means that the vaccine gives only limited protection, if any. Major studies have shown that women who were vaccinatede nevertheless developed cervical cancer,” the Shaare Zedek physician saids.
“If HPV vaccine, however, were proven to prevent cervical cancer, that would be something else,” Beller continued. “But it hasn’t. The US Food and Drug Administration checks for safety of the vaccine, but not for efficacy. There is no evidence that the vaccine protects against cervical cancer, only [that it] counters the virus itself. No decrease in invasive cervical cancer... in the vaccinated population has been documented so far. Australia was the first country to implement a schoolbased mass vaccination program with Gardasil in April 2007.”
The World Health Organization in 2009 recommended the use of HPV vaccines for primary prevention of cervical cancer. But “there is no evidence that prophylactic vaccination against HPV types type 16 and type 18 reduces the incidence of cervical cancer,” Beller declared. As the vaccine costs $100 to $360 for three doses in wealthy countries, it is completely out of the reach of developing countries, where an effective vaccine would be most urgently needed, he continued.
The Shaare Zedek specialist concluded that pediatricians are important advocates for preventive medicine, but they may know little about HPV infection and cervical and other HPV-related cancers. Obstricians/ gynecologist know about HPV and cervical cancer prevention, but they often know little about vaccines and immunization delivery.
DR. DIANE Flescher, an internal medicine specialist and medical director of Jerusalem’s Bishvilaych – Women’s Well-Health Center, said that various questions have been raised by the ministry plans to vaccinate.
“Do Israelis need a vaccine against cervical cancer? Is this the best way to decrease morbidity and mortality from cervical cancer here? Do Israelis need a vaccine against condyloma [genital warts]? Is the vaccine safe and effective? Is it costeffective in Israel? Will parents have to sign a consent form before this vaccination is given? What information will they get and in what languages?” Answering her own questions, Flescher said the death rate in Israel from cervical cancer is very low, and Pap smears have drastically reduced cervical cancer deaths. “The 50% mortality from cervical cancer that is frequently cited sounds like a scary statistic, but this is not ovarian cancer, which means most women are diagnosed at a late stage.
“So how can we save the Israeli women who die from the disease? Don’t invest in a vaccine that has not yet saved even one case of cervical cancer; invest the money instead in public service campaigns. How many young women today know that smoking increases the risk of cervical cancer, or that condoms decrease the risk of contracting the HPV virus that may be associated with this? The radio ads, instead of pushing mothers to vaccinate their daughters, need to encourage women to get Pap smears,” said Flescher.
“Israel needs a national cervical cancer project so the health funds can track women who have not had a Pap smear within the past three years. We also need a centralized, state-of-the art laboratory with welltrained cytologists to interpret Pap smears correctly. These steps will save hundreds of women in Israel in only a few years.”
As for genital warts, Flescher said, “this is not a fatal disease and is treatable. This needs to be addressed in a completely different way; the populations most at risk can be targeted for education. For example, Jerusalem doesn’t have a single sexually transmitted disease clinic. I have to send my patients to Tel Aviv.”
DOCTORS AT the ministry meeting who advocated the vaccination program were just as adamant. Prof.
Shmuel Rishpon, the ministry’s district health officer for Haifa and chairman of the ministry’s advisory board on vaccination, told the Post that this group was enthusiastically in favor.
“Major clinical trials prove that the vaccine prevents 97% of infection from HPVs types 16 and 18 that can cause precancerous growths and genital warts. It’s true that trials didn’t actually prove prevention of cervical cancer – it takes 10 or 20 years to prove [that]. We believe it prevents cervical cancer. But 51 countries have already included it in their regular vaccine schedule, and the organizations that approved it have a lot of prestige and influence.”
Rishpon added that there are many tens of thousands of cases of genital warts and precancerous growths diagnosed in Israel. As for haredi and modern Orthodox women, Rishpon said that while parents may not agree to vaccination in eighth grade, religious institutions such as Machon Puah “told us it would decide whether to recommend that engaged women get the shots. In any case, numerous religious men have sex outside of marriage, and penitent Jews who had sex before marriage are numerous.
Pap smears cause women a lot of anxiety until they get the answers, and there are false-negative and false-positive results. Ethically, a vaccine is better, and there is not the suffering of treating precancerous growths and genital warts. It is primary prevention.”
Prof. Hava Tabenkin, head of family medicine at Afula’s Emek Medical Center and of the Clalit Health Services’ northern district, is another strong advocate of vaccine. “Even if ‘only’ 70 women die of it in a year, it’s absurd to say ‘only.’ It’s a sexually transmitted disease, so some get less excited about it” she told the Post. “One doesn’t die from polio, and the ministry is doing a major vaccination campaign against it.
Vaccination has changed the face of medicine. But people are still suspicious about vaccines.”
She added that the side effects of HPV vaccine were small in number and not proven. “Without the vaccine,” she said, “women will get genital warts and precancerous lesions that are very painful and expensive to treat and some will lose their fertility as a result.”
FINALLY, ISRAEL Cancer Association director-general Miri Ziv took a middle-of-the-road view. “We are for saving lives. Chemotherapy is for stick people. Vaccine is for healthy people. If you give something to healthy young people, you have to make sure that it causes no harm and that it doesn’t cause harmful side effects. Three decades ago, an epidemic of cervical cancer was predicted, but it is not increasing.”
Ziv said that if the government can pay for it and wants to do it, she would not oppose it, “but it has to be done very carefully, with serious monitoring and a major public health campaign.”