HPV Vaccines

The recommendation that all 11-12 year old girls (as well as women up to 26

years of age) be immunized with HPV vaccine was an important public health
milestone. However, mandating this vaccine for school attendance raises a number
of unique social, ethical and moral questions. Before addressing these
questions, let’s consider some issues about

HPV infections and

vaccines as well as about

immunization mandates for school attendance.

1. Infection with HPV types that cause cancer. While some
HPV types are spread by casual contact, other types are acquired by intimate
sexual contact. These are known as genital HPV infections.

Genital HPVs cause cervical cancer—as well as other cancers and genital
warts.

• By 50 years of age, 70-80% of women will have acquired genital HPV
  infection—often with more than one type of HPV.


• Adolescents and young adults are very likely to acquire genital HPV
  infection within a few months after beginning sexual activity.


• A woman can also be infected with HPV by involuntary sexual
  exposure—such as date rape—as well as by her husband (or partner) if he was
  infected from a prior sexual partner, even if she were abstinent until
  marriage.


• Although the vast majority of women recover uneventfully from high-risk
  (cancer causing) genital HPV infections, some of these infections may lead
  to persistent infection, cause abnormal Pap tests, and progress to cervical
  cancer. Regular Pap screening and then the treatment of any abnormalities
  that are detected prevent many HPV infections from causing cervical cancer.
  

2. Vaccines against HPV. Two HPV vaccines have been under
development in the United States and

one of these was licensed in June 2006.

The new vaccines target HPV types 16 and 18, which cause about 70% of the
cases of cervical cancer. However:

• The vaccines do not protect a woman who is infected withe vaccine strain
  of HPV infection before she is vaccinated—that is, vaccine needs to be
  administered prior to exposure to the virus.


• They do not protect against other high risk (cancer causing) strains not
  in the vaccine—therefore, they will not eliminate all HPV-caused cancers.
  Thus, screening and treatment programs will still be needed to reduce
  cervical cancer deaths.
  

Because these vaccines prevent persistent genital HPV infections, they also
may have the potential to reduce the transmission of these particular
strains from person to person.

The vaccines appear to be very safe. Nevertheless, unexpected rare adverse
events may not be detected until after many more people have been immunized.

3. Vaccine recommendations and school mandates. The
individual states determine which vaccines should be required for school and
daycare entry based on the public health needs of the state, usually based upon
the Centers for Disease Control and Prevention (CDC) recommendations. States
require that school children be immunized against certain diseases to protect
bothe the vaccine recipient and his/her schoolmates from contagious illnesses.

State requirements differ.

• School mandates have increased immunization levels and have reduced
  disease outbreaks, including among those who cannot receive the vaccine
  because of medical reasons.


• Most states permit religious and/or philosophical exemptions, in
  addition to exemptions for medical contraindications.


• Children who have been exempted from compulsory immunization for
  religious or philosophical reasons are many times more likely to both
  acquire and spread vaccine-preventable diseases.

4. Universal HPV immunization of school girls. The CDC has
made a

universal recommendation for girls 11-12 years of age to receive the HPV
vaccine (as well as older girls and women):

• A universal recommendation helps remove the social stigma associated
  with receiving the HPV vaccine; that is, girls or women who receive the
  vaccine should not be considered to be “more likely to engage in risky
  sexual behavior” than their peers.


• A universal recommendation makes the vaccine eligible for funding
  through the
  Vaccines For Children (VFC) program. In addition, any serious adverse
  events associated with the vaccine can be addressed under the
  
  Vaccine Injury Compensation Program.
  

Prevention of genital HPV infections

Avoiding HPV exposure. HPV infections are usually without
symptoms and can last for decades. For that reason, it is not possible to
accurately assess the risk of acquiring a genital HPV infection from any
specific sexual partner.

• Total sexual abstinence is logically the best protection against
  acquiring all sexually transmitted infections, including genital HPVs.
  However, it will not protect a woman against involuntary exposure such as
  date rape and is not a very practical long term strategy.


• Abstinence until marriage does not protect a woman if her husband is
  infected from a prior sexual partner.


• Monogamy by both sexual partners could possibly assure a woman’s
  protection—but only if both partners have been abstinent and they remain
  strictly monogamous.
  

Limiting HPV exposures.

Sexual behaviors are the most important risk factors for acquiring genital
HPV infection. Delaying sexual intercourse and limiting the number of sexual
partners could reduce the risk of HPV infection. But:

• More than 7% of high school students have their first sexual intercourse
  before 13 years of age and 62% of girls and 70% of boys have had sexual
  intercourse by the end of 12th grade. By ninth grade, almost 11% have had
  more than four sex partners.


• Consistent condom use may or may not provide some protection against
  acquiring HPV—but condoms do protect against other sexually transmitted
  infections, some of which may relate to whether her HPV infection progresses
  to cervical cancer or not.
  

Preventive HPV Vaccines. The most effective strategy to
prevent HPV infection with the strains in the vaccine (which cause 70% of the
cases of cervical cancer) is to immunize women before they become infected. That
is why immunization is recommended for all girls at 11-12 years of age. However:

• The current HPV vaccines will not protect against other strains of HPV.
  Thirty percent of cervical cancers are due to infection with strains not
  included in the vaccine.


• It is not yet known how long vaccine-induced immunity will last.

Compulsory HPV immunization. Mandating HPV immunization for
school entry would increase the proportion of girls and women who are
immunized—and therefore immune to the HPV types in the vaccine—before most of
them will be exposed. This is the most compelling argument in favor of mandating
this vaccine.

Others argue that HPV mandates are not appropriate because school

immunization laws are intended to control outbreaks of contagious diseases—such
as measles, diphtheria and others—that can spread easily to other school
children in the classroom. HPV is spread only by intimate sexual contact.

Other factors to consider are:

• 
  
  Costs of the vaccine. The vaccine is expensive (about $120 per
  dose for the three shot series). To be most effective, a girl needs to
  receive the entire 3 dose series, which requires three healthcare visits
  (two more than is usual). The VFC and some health insurance plans cover the
  costs of the 3 HPV vaccine doses and clinic visits. But not all families
  have insurance, not all insurance plans cover HPV vaccine, and most children
  are not VFC eligible.


• Possible vaccine-associated disparities. Poorer women
  are more likely to develop HPV infection and develop cervical cancer. If
  poor women can not afford to get the vaccine, this disparity could become
  greater. However, compulsory HPV vaccination could reduce the disease burden
  disparity by assuring all socioeconomic groups of women obtain the vaccine.
  Whether HPV immunization is compulsory or not, the cost of the vaccine will
  keep some girls and women from receiving the vaccine.


• 
  
  Exemptions to compulsory immunization. Many parents and young
  women who feel that laws requiring HPV immunization would conflict with
  their beliefs and their personal liberties—or cost too much—would have a
  means of opting out of compulsory HPV immunization. A possible, unintended,
  adverse consequence then could be that people who opt out of HPV vaccine
  might also opt out of other vaccines intended for this age group.

Could other mandates provide insight? Hepatitis B (HBV), like HPV, is largely a sexually transmitted infection that can lead to liver cancer. HBV vaccine is recommended at birth and most states require HBV immunization for day care and school entry. However, mandates for HBV vaccine are different, because as many as 30% of HBV infections have no known sexual contacts (or other high risk behaviors). Tetanus is a serious, life threatening illness that is not spread from person to person but which is, nevertheless, required for school and day care attendance. However, all diphtheria and pertussis vaccines include tetanus as a component. Bicycle helmets and infant car seats are compulsory for children in some communities.

Other Issues

Parental Concerns

Parental acceptance of HPV vaccines for their 11-12 year old daughters will
affect whether the vaccine is widely used in this age group. Most (75%) parents
in a recent

California study indicated that they would likely give their daughters the
HPV vaccine before the age of 13 years in order to keep their daughters safe.
However, 25% of parents have reservations about having their daughters immunized
at that age. The reasons they gave were their concern that vaccination might
influence their daughter’s sexual behaviors, their uneasiness about the morality
of immunizing to prevent sexually transmitted infections, and worries about the
safety of the vaccine.

• Will girls and women who receive the HPV vaccine be more likely
  to engage in risky behavior? Preventing other sexually transmitted
  infections such as HIV (the cause of AIDS), gonorrhea, genital herpes etc.
  through abstinence and safe sex practices remains important for girls to
  understand. It seems unlikely that a vaccine that prevents a small number
  sexually transmitted infections which have no symptoms would cause girls to
  be promiscuous or have unsafe sex, as some have suggested. However, there is
  no evidence to support or refute this concern.


• Potential adverse events from the HPV vaccine. Since
  our experience with this new vaccine is limited and not all women are
  exposed to high risk HPVs, some girls could experience rare vaccine adverse
  events not yet identified without a corresponding benefit.

Will immunized women stop seeking cervical cancer screening programs?


Some have speculated that HPV-immunized women might not participate in cervical
cancer screening programs, thinking that they are not at risk anymore. The truth
is that they remain at risk for other high risk HPV infections and any
pre-existing HPV infection that they may have acquired prior to HPV
immunization. There is no evidence to support or refute this concern either.

Will universal HPV immunization reduce transmission of vaccine-strain
HPVs?

Although universal HPV vaccination may well reduce the transmission of the
vaccine type strains, there is no data that addresses this issue. However, it
seems unlikely that universal immunization of girls and young women would reduce
transmission, in the absence of an intervention to prevent transmission by and
to men. Data concerning the safety and effectiveness of the vaccine for boys and
men is being collected but is not available yet.

Gardasil Vaccine Ingredients - Roach Killer, Aluminum, and Polysorbate 80

Manufactured by Merck, the proud maker of Vioxx, the Gardasil vaccine is perhaps one of the most controversial vaccines to date. The push to mandate this, which supersedes the individuals rights to choose how to care for their own health. Should the vaccine prove 10 to 15 years from now to be a sterilizing agent, we would lose and entire generation of child bearing girls, and do not think it cannot happen. Gardasil vaccine ingredients include amorphous aluminum hydroxyphosphate sulfate, sodium chloride, L-histidine, polysorbate 80, sodium borate, (roach killer), and water for injection.

Gardasil vaccine ingredients - Polysorbate 80: Although Polysorbate 80 is a food additive that enables solubility of flavoring oils with water, injection is quite different. Polysorbate 80 injected into prepubescent rats caused a rapid growth of reproductive organs, but growth was abnormal and the rats were sterile, unable to have children. When used intravenously with vitamins it has been known to cause anaphylactic shock. According to the Polysorbate 80 MSDS, it may be a carcinogenic, (cause cancer), as well as a mutagenic, (birth defects).

Sodium Borate, AKA Roach Killer: From the National Library of Medicine, "Sodium borate is no longer used in medical preparations", until now. The U.S. National Library of Medicine and the National Institutes of Health declares Sodium Borate to be a dangerous poison. Two of the medical uses of the past were for disinfecting wounds, until people started dying from repeated cleaning), and cleaning nursery's, (until too many babies started dying) Side effects of Roach killer, I mean Sodium borate are vomiting, diarrhea, skin rash, blisters, collapse, coma, convulsions, drowsiness, fever, lack of desire to do anything, low blood pressure, decreased urine output, sloughing of the skin, twitching of facial muscles, arms, hands, legs, and feet.

Amorphous Aluminum Hydroxyphosphate Sulphate: Aluminum is a serious neurotoxin and has been linked to Alzheimer's, autopsies have shown Alzheimer's patients to have a build up of aluminum around dead brain tissue. People who have received their flu shots for 5 years in a row have a 10 fold increased risk of Alzheimer's. Aluminum Salts are used as an adjuvant, in other words they stimulate the body's immune system. Amazingly I cannot find an MSDS sheet for this, however aluminum phosphate, (very similar aluminum salt) is hazardous in case of skin contact (irritant), of eye contact (irritant), of ingestion, of inhalation. Corrosive to eyes and skin. The amount of tissue damage depends on length of contact. Eye contact can result in corneal damage or blindness. Skin contact can produce inflammation and blistering. Inhalation of dust will produce irritation to gastro-intestinal or respiratory tract, characterized by burning, sneezing and coughing. Severe over-exposure can produce lung damage, choking, unconsciousness or death. Obviously when injected the contact remains until the body can flush this out.

Gardasil was tested for 5 years, not long enough to know if 9 year old girls are going to be sterile or if they will have birth defects in their offspring. The Gardasil vaccine ingredients are among the worst list of ingredients of any vaccine I have read the ingredients of so far.

Disclaimer: This article, "Gardasil Vaccine Ingredients" is not intended to give medical advice. It is a call to educate yourself so that in making a decision where your child is concerned, you should take an active role in learning all you can from medical experts on both sides of the fence, then make an educated decision. we did not make an informed decision until one son got Leukemia and another developed Autism immediately after receiving his MMR vaccine. This has sent us on a quest to inform ourselves and others to seriously question what kind of toxic soups are being injected with the vaccines. Odds are if your child is injured by a vaccine, you have little or no recompense against the industry.

Cervarix

Cervarix is a vaccine against certain types of the human papillomavirus (HPV).

Cervarix is designed to prevent infection from HPV types 16 and 18, which currently cause about 70% of cervical cancer cases. Type 16 is also associated with oropharyngeal squamous-cell carcinoma, a form of throat cancer. Additionally, some cross-reactive protection against virus strains 45 and 31 were shown in clinical trials. Cervarix is also formulated with AS04, a proprietary adjuvant that has been found to boost the immune system response for a longer period of time.

Indications

Cervarix is a preventative cervical cancer vaccine, not therapeutic. HPV immunity is type-specific, so a successful series of Cervarix shots will not block infection from cervical cancer-causing HPV strains other than HPV 16, 18, 31 and 45, so experts continue to recommend routine cervical Pap smears even for women who have been vaccinated.

Biotechnology

Cervarix is created using the L1 protein of the viral capsid. Recombinant activity in a baculovirus vector produces L1 protein spheres, which are very immunogenic. The viral proteins induce the formation of neutralizing antibodies. The vaccine contains no live virus and no DNA, so it cannot infect the patient. The vaccine was developed, in parallel, by researchers at Georgetown University Medical Center, the University of Rochester, the University of Queensland in Australia, and the U.S. National Cancer Institute.

Clinical trials

Phase II trials demonstrated 100% protection of the vaccine against types 16 and 18 HPV, including among 1100 women from North America and Brazil. Phase III trials included over 660 women from Germany and Poland. Company officials are now conducting a clinical trial to determine whether Cervarix is more effective than rival Merck's HPV vaccine Gardasil.

Longevity of the vaccination has proven so far to be at least 5.5 years. In the clinical trials, women were given three doses over a six-month span -- at 0 month, 1 month, and 6 months. The technology used in this vaccine was licensed from the University of Rochester.

Regulatory Approval

• Australia - It received approval in May 2007 in Australia for women ages 10 to 45.
• Philippines - On August 25, 2007 GlaxoSmithKline launched Cervarix in the Philippines after approval by the local Bureau of Food and Drugs.
• European Union - It was approved in September 2007 in the European Union.
• United States of America On March 29, 2007 GlaxoSmithKline submitted a Biologics License Application (BLA) for Cervarix (human papillomavirus vaccine, AS04 adjuvant-adsorbed), to the FDA which included data from clinical trials in almost 30,000 females 10 to 55 years of age and contains data from the largest Phase III cervical cancer vaccine efficacy trial to date.
• GSK awaiting results of further trials to submit to the FDA. Approval is not expected before late 2009.

Use

Cervarix is used by the UK government for its national programme of vaccination for teenage girls. This caused some controversy since Cervarix was chosen over Gardasil apparently for cost reasons, even though Gardasil protects against HPV strains 6 and 11 in addition to 16 and 18.

Gardasil

Gardasil (Merck & Co.), also known as Gardisil or Silgard, is a vaccine against certain types of human papillomavirus (HPV).
Gardasil is designed to prevent infection with HPV types 16, 18, 6, and 11. HPV types 16 and 18 currently cause about 70% of cervical cancer cases, and also cause some vulvar, vaginal, penile and anal cancers[5]. HPV types 6 and 11 cause about 90% of genital warts cases.
Human papillomavirus (HPV) infections cause nearly all cases of cervical cancer. Cervical cancer is the fifth leading cause of death from cancer in women world-wide[6], and the leading cause of cancer-related deaths among women in the majority of developing countries.
Gardasil is only effective in preventing HPV infections, not in treating those already infected by HPV, and so the vaccine must be given before HPV infection occurs in order to be effective. For this reason it is recommended to administer the vaccine before adolescence and the onset of sexual activity.
Gardasil can also be used to vaccinate males.

History

The research that led to the development of the vaccine began in the 1980s by groups at the University of Rochester, Georgetown University, and the US National Cancer Institute. In 1991 investigators at the University of Queensland found a way to form non-infectious virus-like particles (VLP), which could also strongly activate the immune system. However, these VLPs assembled poorly and did not have the same structure as infectious HPV. In 1993, a laboratory at the US National Cancer Institute was able to generate HPV16 VLPs that were morphologically correct. These VLPs were the basis for the HPV16 component of the Gardasil vaccine. The history of the discovery of this vaccine is described by McNeil. Upon commercialization of the vaccine, controversy involving intellectual property arose between the various groups that played a role in developing the vaccine.

Clinical trials

Merck & Co. conducted a Phase III study named FUTURE II. This clinical trial was a randomized double-blind study with one controlled placebo group and one vaccination group. Over 12,000 women aged 16–26 from thirteen countries participated in the study. Each woman was injected with either Gardasil or a placebo on Day 1, Month 2, and Month 6. In total, 6,082 women were given Gardasil and 6,075 received the placebo. Merck has tested the vaccine in several hundred 11- and 12-year-old girls. On February 27, 2006, the independent Data and Safety Monitoring Board recommended the clinical trials be terminated on ethical grounds, so that young women on placebo could receive Gardasil.

Indications and prevalence

Gardasil is a prophylactic HPV vaccine, meaning that it is designed to prevent the initial establishment of HPV infections. For maximum efficacy, it is recommended that girls receive the vaccine prior to becoming sexually active. However, women who were already infected with one or more of the four HPV types targeted by the vaccine (6, 11, 16, or 18) were protected from clinical disease caused by the remaining HPV types in the vaccine.
Since Gardasil will not block infection with all of the HPV types that can cause cervical cancer, the vaccine should not be considered a substitute for routine pap smears.
Fewer HPV infections mean fewer complications from the virus and less time and money spent on the detection, work-up, and treatment of cervical cancer and its immediate precursor, cervical dysplasia. It prevents infertility caused by cervical biopsies and reduces the severe respiratory problems of children who are infected by HPV from their mothers. In addition, protection against HPV 6 and HPV 11 is expected to eliminate 90% of the cases of genital warts. Gardasil also protects against vulvar and vaginal cancers caused by HPV types 16 and 18.
Merck is seeking FDA approval to market Gardasil to older women aged 27 to 45. As of early part of 2009, FDA has requested final trial data before it approves the drug for this age group.

Use in males

Gardasil is also effective in males, providing protecton against genital warts and some potentially precancerous lesions caused by some HPV types. An ongoing study of 4,065 males demonstrated the efficacy of Gardasil in males who did not have HPV infection prior to vaccination. The vaccination is expected to protect against penile cancer and anal cancer caused by included HPV types, and research in this area is still underway.
In December 2008, Merck asked the FDA for permission to market the vaccine in the United States for males between ages 9 to 26. In the UK HPV vaccines are already licensed for males aged 9 to 15 and for females aged 9 to 26.
Gardasil is in particular demand among gay men, who are at significantly increased risk for genital warts and anal cancer caused by HPV.
HPV vaccines may be useful in preventing anal cancer caused by HPV types 16 and 18. A 2005 study in San Francisco found that 95 percent of HIV-infected gay men also had anal HPV infection, of which 50 percent had precancerous HPV-caused lesions. Type 16 is also associated with oropharyngeal squamous-cell carcinoma, a form of throat cancer.

Administration

Gardasil is given in three injections over six months. The second injection is two months after the first, and the third injection is four months after the second shot is administered.

Biotechnology

The HPV major capsid protein, L1, can spontaneously self-assemble into virus-like particles (VLPs) that resemble authentic HPV virions. Gardasil contains recombinant VLPs assembled from the L1 proteins of HPVs 6, 11, 16 and 18. Since VLPs lack the viral DNA, they cannot induce cancer. They do, however, trigger an antibody response that protects vaccine recipients from becoming infected with the HPV types represented in the vaccine.

Public health advantages

According to the American Centers for Disease Control, getting as many girls vaccinated as early and as quickly as possible will reduce the cases of cervical cancer among middle-aged women in 30 to 40 years and reduce the transmission of this highly communicable disease. Unfortunately, there are hurdles to getting this done. These include the limited understanding by many people that HPV causes cervical cancer, the difficulty of getting pre-teens and teens into the doctor’s office to get a shot, and the high cost of the vaccine ($120/dose, $360 total for the three required doses, plus the cost of doctor visits).

In the United States it is believed that one way to bring down the cost of the vaccine and to educate the public on the benefits of vaccination is to make it mandatory for girls entering school. This approach has been taken with vaccines for mumps, measles, rubella, and hepatitis B (which is also sexually transmitted) so many state legislators have penned bills that do this. Almost all pieces of legislation currently pending in the states that would make the vaccine mandatory for school entrance have an "opt-out" policy.

The National Cancer Institute writes, "Widespread vaccination has the potential to reduce cervical cancer deaths around the world by as much as two-thirds, if all women were to take the vaccine and if protection turns out to be long-term. In addition, the vaccines can reduce the need for medical care, biopsies, and invasive procedures associated with the follow-up from abnormal Pap tests, thus helping to reduce health care costs and anxieties related to abnormal Pap tests and follow-up procedures (2)."

Efficacy

The National Cancer Institute says, "FDA-approved Gardasil prevented nearly 100 percent of the precancerous cervical cell changes caused by the types of HPV targeted by the vaccine for up to 4 years after vaccination." The vaccine is believed to be effective for longer, but for how long, and whether a booster shot will be needed is still being studied.

Darren Brown, Indiana University, reported at the 2007 Interscience Conference on Antimicrobial Agents and Chemotherapy that Gardasil had 38% efficacy against 10 other HPV types responsible for >20% of cervical cancer cases.

Safety

According to the Centers for Disease Control, the vaccine was tested in over 11,000 women and girls (ages 9 to 26). The Food and Drug Administration and Centers for Disease Control say that the vaccine has only minor side effects, such as soreness around the injection area. The FDA and CDC consider the vaccine to be safe. It does not contain mercury, thiomersal or live virus or dead virus, only virus-like particles, which cannot reproduce in the human body. Merck, the manufacturer of Gardasil, will continue to test women who have received the vaccine to determine the vaccine's efficacy over the period of a lifetime.

Fainting is more common among adolescents receiving the Gardasil vaccine than in other kinds of vaccinations. Patients should remain seated for 15 minutes after they receive the HPV vaccine. There have been reports that the shot is more painful than other common vaccines, and the manufacturer Merck partly attributes this to the virus-like particles within the vaccine. General side effects of the shot may include joint and muscle pain, fatigue, physical weakness and general malaise.

As of 30 June 2008, out of over 16 million doses of Gardasil distributed in the United States, there have been 9,749 reports to the Vaccine Adverse Event Reporting System (VAERS) following Gardasil vaccination. Gardasil has less than half the average percentage of serious reports. "It is important to note that a report to VAERS does not mean there is a connection between the vaccine and the event. It means the event took place following vaccination."[30] The FDA and CDC said that with millions of vaccinations “by chance alone some serious adverse effects and deaths” will occur in the time period following vaccination, but have nothing to do with the vaccine. Although at least 20 women who received the Gardasil vaccine have died, there is no evidence that deaths or serious outcomes were connected to the shot. Where information was available, the cause of death was explained by other factors. Likewise, although a small number of cases of Guillain-Barré Syndrome (GBS) have been reported following vaccination with Gardasil., there is no evidence linking GBS to the vaccine.
The FDA and CDC monitor events to see if there are patterns, or more serious events than would be expected from chance alone.

Long-term impact

This article or section needs to be updated. Please update the article to reflect recent events or newly available information, and remove this template when finished.
One unknown property of the vaccines now being researched is the persistence of their protective effects. Since the Gardasil vaccine has been administered for only a few years now, it is unknown whether it will provide life-long immunity to recipients. In coming decades, further study will answer this question.

Whether the effects are temporary or life-long, widespread vaccination could have a substantial public health impact. 270,000 women died of cervical cancer worldwide in 2002. Acting FDA Administrator Dr. Andrew von Eschenbach said the vaccine will have "a dramatic effect" on the health of women around the world.[34] Even in the United States, where screening programs are routine, the National Cancer Institute estimated that 9,700 women would develop cervical cancer in 2006, and 3,700 would die.

Merck and CSL Limited are expected to market Gardasil as a cancer vaccine, rather than an STD vaccine. It remains unclear how widespread the use of the three-shot series will be, in part because of its $360 list price ($120 each for three shots). Merck and CSL have also suggested that governments make vaccination with Gardasil mandatory for school attendance, which has upset some conservative groups and libertarian groups.[36][34][37] Many such groups also expressed fears that vaccination with Gardasil might give girls a false sense of security regarding sex and increase their level of promiscuity. According to the Cleveland Clinic, "Genital HPV is spread through direct skin-to-skin contact with someone who has an HPV infection. Contact includes vaginal, anal, and oral sex. Some types of HPV cause genital warts, which are hard, rough lumps that develop on the skin. Anyone who is sexually active can get HPV and genital warts." The types of HPV the vaccine treats are transmitted by sexual activity.
Both men and women are carriers of HPV. To eradicate these strains, males might eventually need to be vaccinated. Studies are being conducted now to determine the efficacy of vaccinating males with the current vaccine.

Cost effectiveness

Studies using different pharmacoeconomic models predict that vaccinating young women with Gardasil in combination with screening programs may be more cost effective than screening alone. These results have been important in decisions by many countries to start vaccination programs. For example the Canadian government approved $300 million to buy the HPV vaccine in 2008 after deciding from studies that the vaccine would be cost-effective especially by immunizing young women. Marc Steben, an investigator for the vaccine, wrote that the financial burden of HPV related cancers on the Canadian people was already $300 million per year in 2005, so the vaccine could reduce this burden and be cost-effective.

Since penile and anal cancers are much less common than cervical cancer, HPV vaccination of young men is likely to be much less cost-effective than for young women.

Cervical cancer vaccine

What the human papilloma virus (HPV) is

There are over 100 different types of human papilloma virus (HPVs). It is sometimes called the ‘wart virus’ or ‘genital wart virus’ as some types of HPV cause genital warts. The virus is passed on from one person to another through sexual contact.

Many women will be infected with the HPV virus at some time during their lifetime. Often the virus causes no harm and goes away without treatment.

HPV and cancer

HPV can increase the risk of developing cervical cancer. Cervical cancer is cancer of the neck of the womb. About 3,000 women are diagnosed with this type of cancer every year in the UK. Most women infected with HPV don’t go on to develop cervical cancer. But for some, infection with HPV can go on to cause

• Genital warts
• Changes in the cervix, which may develop into a cancer
• Changes in the vaginal tissues, which may develop into vaginal cancer

Of the different types of HPV, types 16 and 18 cause about 7 out of 10 (70%) cancers of the cervix. Most of the remaining 30% of cervical cancers are associated with other high risk HPV types. HPV types 6 and 11 cause genital warts but are less likely to cause cancer.

You can find out more about the risks and causes of cervical cancer in the cervical cancer section of CancerHelp UK. HPV is also a risk factor for other types of cancer including vaginal cancer, vulval cancer, anal cancer and cancer of the penis.

Research into vaccines to prevent HPV

Several research trials have tested vaccines as a way of preventing infection with HPV. A trial testing Gardasil called FUTURE II reported its results in October 2005. This phase 3 trial involved over 12,000 women aged between 16 and 26. These women did not have HPV before the start of the trial. The women were divided into two groups. Half the women were given Gardasil and the other half had a dummy vaccine (placebo). Both groups of women had 3 injections of either the vaccine or placebo over six months. Over the following two years the women had regular checks to see if they had got HPV, or had any precancerous changes to the cells of the cervix, which could develop into a cancer. The group who had the vaccine showed no precancerous changes. Of the 5,258 women who had the placebo, 21 had precancerous changes, which is 0.4%. The researchers found that Gardasil protected against HPV types 6 and 11, as well as 16 and 18.

Two other phase 3 trials have tested the vaccine Cervarix. The first was for women under 26 and closed in July 2005. It involved over 18,000 women from all over the world, including the UK. This study was called ‘PATRICIA’ (PApilloma TRIal to prevent Cervical cancer In young Adults). The second was for women of 26 and over, and closed in August 2006. On the basis of results from these trials, the European Commission has approved Cervarix for the prevention of precancerous changes in the cervix in girls and women between the age of 10 and 25.

The HPV vaccination programme

In the UK, girls in year 8 at school (aged 12 to 13) are offered the HPV vaccine. The vaccine the Government has chosen to use is Cervarix. Girls have three injections over 6 months given by a nurse. A letter about the vaccine and a consent form is sent to the parents of the girl before she has the vaccine. It is up to her whether she has the vaccine. A 2 year 'catch up' programme also started in Autumn 2008, to vaccinate girls aged between 13 and 18. The NHS immunisation website has more information about the vaccination programme and when girls in the catch up programme will be offered the vaccine.

It is also possible to have the vaccination privately. The cost for private treatment varies from doctor to doctor. We are hearing reports of about £500 being charged for a course of 3 injections.

This research means that if girls take up the vaccination the programme will prevent at least 7 out of 10 cancers of the cervix and possibly even more in the future. But it takes between 10 and 20 years for a cancer to develop after HPV infection. So any benefits in reducing cervical cancer won’t be seen for quite a long time. But the number of cases of pre-cancerous changes in the cervix (CIN) will fall quite rapidly.

It is not certain how long the vaccination gives protection for. So far the trials have followed people up for 6 years so we know that it lasts at least this long. More research is needed to find out how long it lasts and if women need a booster dose at some time.

Side effects of the vaccine

The side effects are usually mild and include

• Headache
• Aching muscles
• Redness and soreness around the site of the injection
• Fever
• Feeling and being sick
• Stomach pain
• Diarrhoea
• Itching, rash
• Dizziness

Do we still need cervical cancer screening?

We'll still need the cervical screening programme in the UK, even after the vaccines become widely available. The vaccines don't prevent infection with all types of HPV. Also from the research so far, we don't think the vaccines will help prevent cervical cancer in women already infected with HPV. And it takes about 10 to 20 years after HPV infection for a cervical cancer to develop.

So it’s very important to remember that women will still need cervical cancer screening (smear tests) for many years to come. There is more information about cervical cancer screening in the cervical cancer section of CancerHelp UK.

A UK trial is planned to look at a vaccine to treat women already infected with HPV. You can find out more about the latest research into cervical cancer in the cervical cancer section of CancerHelp UK.

Wide Use of HPV Vaccines

Two vaccines against cervical cancer are being widely used without sufficient evidence about whether they are worth their high cost or even whether they will effectively stop women from getting the disease, two articles in this week’s New England Journal of Medicine conclude.
Both vaccines target the human papillomavirus, a common sexually transmitted virus that usually causes no symptoms and is cleared by the immune system, but which can in very rare cases become chronic and cause cervical cancer.

The two vaccines, Gardasil by Merck Sharp & Dohme and Cervarix by GlaxoSmithKline, target two strains of the virus that together cause an estimated 70 percent of cervical cancers. Gardasil also prevents infection with two other strains that cause some proportion of genital warts. Both vaccines have become quick best sellers since they were licensed two years ago in the United States and Europe, given to tens of millions of girls and women.

“Despite great expectations and promising results of clinical trials, we still lack sufficient evidence of an effective vaccine against cervical cancer,” Dr. Charlotte J. Haug, editor of The Journal of the Norwegian Medical Association, wrote in an editorial in Thursday’s issue of The New England Journal. “With so many essential questions still unanswered, there is good reason to be cautious.”

In her article, Dr. Haug points out the vaccines have been studied for a relatively short period — both were licensed in 2006 and have been studied in clinical trials for at most six and a half years. Researchers have not yet demonstrated how long the immunity will last, or whether eliminating some strains of cancer-causing virus will decrease the body’s natural immunity to other strains.

More to the point, because cervical cancer develops only after years of chronic infection with HPV, Dr. Haug said there was not yet absolute proof that protection against these two strains of the virus would ultimately reduce rates of cervical cancer — although in theory it should do so.
Dr. Richard Haupt, medical director of Merck, called these concerns “very theoretical,” noting that continuing research and monitoring suggested that immunity would be longlasting and that the vaccine would not lead to problems with other strains.

He added that cervical cancer was “just the tip of the iceberg” and that HPV caused a huge amount of expensive and stressful testing in developed nations that could be avoided with vaccination.

The vaccines, which require three shots for a complete series, cost about $400 to about $1,000, depending on the country and the fees for doctors’ visits. Unlike older vaccines that save money by preventing costly disease, these vaccines cost health systems money.

The second paper published this week, a study by Jane J. Kim and Dr. Sue Goldie of Harvard, looks at the issue of costs and concludes that the vaccines will be cost effective only if used in certain ways. In particular, the researchers say the vaccines will be worth the cost only if they prove to protect girls for a lifetime, and if current methods for screening for cervical cancer using Pap smears can be safely adjusted to reduce costs there. Further research is required in both areas.

“I believe the vaccine is a great advance, but we have to implement it properly to get the benefits, and that hasn’t happened,” said Dr. Philip Davies of the European Cervical Cancer Association.

In developed countries, Pap smear screening and treatment have effectively reduced cervical cancer death rates to very low levels already. There are 3,600 deaths annually from cervical cancer in the United States, 1,000 in France and 400 in Britain.

Cervical cancer, like skin cancer, can generally be caught at precancerous or non-invasive stages and treated. Because the vaccine prevents infection with only some of the cancer-causing strains, Pap smear screening must continue even in those who are vaccinated.

The Harvard study concluded that giving the vaccine to 12-year-olds would cost $43,600 for every “quality adjusted year of life” it saved by preventing a cancer death; that price would often be considered acceptable by health officials in wealthy countries, experts say.

Dr. Haupt said the study proved that it was best to vaccinate early. “It underscores the value of vaccinating pre-adolescent girls,” since the vaccine works fully only in girls who have not been exposed to HPV.

But if the vaccine were given to all girls and women up to age 21, the cost per year of life saved would be far higher — $120,400, the Harvard study concluded. And if the vaccines prove to require a booster shot, as many critics believe, that cost rises to $140,000. In such cases it might make more economic sense to rely on Pap smear screening alone, the researchers said.