Vaccine against papillomavirus

Papilloma

In recent years, a number of vaccines against the human papillomavirus have entered the routine immunization program.

Every launch of a new vaccine is accompanied by birth cords, from logistical difficulties to claims against the safety of the vaccine. The papillomavirus vaccine has suffered (and suffers) from poor public relations and many problems (when to vaccinate? Only girls? Why also boys? Why in eighth grade?), Which led to a low response rate (about 50%) to the vaccine in schools.

Therefore, the purpose of the information in this chapter is to answer many questions I am asked in the context of the vaccine against the papilloma virus.

What is the human papillomavirus and what disease does it cause in humans?

The human papillomavirus is a very common virus that is transmitted primarily through sexual contact. In fact, this virus is the most common sexually transmitted disease in the world.

About 80% of sexually active men and women will be infected with one of the virus strains during their lifetime.

The infection is usually asymptomatic so a person who is infected is unaware that he or she is infected and does not know that he or she could potentially infect other people.

In terms of morbidity, in women, the virus can cause genital warts, precancerous lesions (in the vagina and cervix) and even cancer (in the vagina, cervix, anus, mouth and pharynx).

In men, the virus can cause genital warts, precancerous lesions (in the anus) and cancer (in the penis, anus, mouth and pharynx).

Diseases caused by the virus usually develop months after the infection (in the case of genital warts) or many years after infection in the case of precancerous lesions or cancer.

What is the connection and how could a virus cause cancer?

After infection, the papilloma virus enters the cells of the body (for example, cells in the cervical region) and can cause over-activation of the cell, uncontrolled cell division and cancer of the cell.

What are the ways of transmitting the virus from person to person?

Papillomavirus infection occurs by direct contact mainly during vaginal, anal or oral sex. Using a condom greatly reduces the incidence of infection but does not completely prevent it.

What's the matter with the different strains of human papillomavirus?

In fact, the papilloma virus is a collective name of a family of over 200 different strains of the virus. Most strains do not cause disease. There are strains that cause genital warts in both women and men. These varieties are classified as "low risk" varieties. Two of these strains – strains number 6 and 11 cause about 90% of genital warts in women and men.

Other strains on the other hand can cause different types of cancer and are therefore classified as "high risk" strains. For example, strains number 16 and 18 are responsible for, among other things, 70% of cervical cancers and 85% of rectal cancers in women and men.

What is the prevalence of morbidity in the State of Israel?

According to data from the Ministry of Health, at any given time, about 20,000 sexually active women and men in Israel suffer from genital warts.

According to data from the Ministry of Health, about 100 people are diagnosed with oral and pharyngeal cancer every year in Israel, with about 70% of these cancers in men and women being caused by the virus.

The human papillomavirus is responsible for about 99% of cervical cancers. According to data from the Ministry of Health, approximately 1,200 to 2,000 women are diagnosed each year in Israel with pre-malignant changes in the cervix. About 180 women (mostly in their 30s and 40s) are diagnosed with cervical cancer each year in Israel and about 80 women die each year from this cancer.

According to the latest data from the Ministry of Health, in 2015 there were 809 cases of the most severe pre-cancerous lesions, 267 women were diagnosed with cervical cancer and 78 women died from this cancer.

According to data from the Ministry of Health, about 60 people, women and men, are diagnosed with rectal cancer every year in Israel. 90% of the above cancers are caused by the papilloma virus.

What type of vaccine is this?

All three vaccines are made from virus-like particles, including the virus’ important shell protein. All three vaccines do not contain a viral genetic material and therefore cannot cause infection.

The three vaccines are active vaccines, ie their purpose is to create antibodies by the vaccinated body (the body is active).

What are the existing vaccines against this virus and how are they different from each other?

There are currently three vaccines against this virus in Israel (and around the world).

Gardasil – Made by MSD – vaccinates against 4 strains of the virus which are 6/11/16/18 (two strains "high risk" and two "low risk").

Gardasil 9 – Made by MSD – vaccinates against 9 strains of the virus which are 6/11/16/18/31/33/45/52/58 (seven strains "high risk" and two "low risk").

Cervarix Made by GSK – vaccinates against two varieties that are 16/18 ("high risk" varieties).

For what gender and at what age are each of the vaccines registered?

Is there a preference for one of the three vaccines?

Definitely yes.

Depending on age and gender, if possible there is a clear preference for the Gardasil 9 vaccine.

The preference over the other two vaccines is clear in light of higher strain coverage.

In fact there is no need for the other two vaccines (Gardasil 4 and Cervarix) and therefore I will now focus only on data on Gardasil vaccine.

Is there any experience in the world with this vaccine (referring to Gradsil or Gradsil 9)?

The vaccine was approved in 2006 and is slowly coming into use in many countries. In the US the vaccine has been in use since June 2006.

The vaccine has been introduced into the vaccination routine in many countries including Australia, the United States, England, Belgium, Canada, Germany, Brazil, New Zealand, Norway, Sweden, Spain, Switzerland, the United Kingdom and more.

As of the end of 2017, over 270 million doses of the various papilloma vaccines have been given worldwide.

What is the effectiveness of the Gardasil vaccine?

In randomized, controlled clinical trials lasting several years, high efficacy of the vaccine has been demonstrated in preventing the transmission of strains that the vaccine protects from them, in preventing genital warts, and in reducing the development of precancerous lesions.

The effectiveness of the Gardasil 9 vaccine has also been tested on tens of thousands of girls and boys around the world.

Today, more than a decade after the marketing of the Gardasil vaccine began in various countries around the world, there are many studies showing the effectiveness of the vaccine in the real world (meaning, not just in a research setting).

Studies demonstrate maximum efficacy in the vaccine especially when vaccinated before exposure to the virus (having sex).

In terms of efficiency demonstrated:

  • About 90% reduction in infection with the strains against which the vaccine gene is used (6/11/16/18).
  • A reduction of about 90% in genital warts.
  • About 85% reduction in severe pre-cancerous lesions in the cervix.

There is already early evidence showing less cases of cancer caused by the papilloma virus among women who have been vaccinated compared to women who have not been vaccinated.

In the male population, the vaccine demonstrated an effectiveness of about 90% in preventing genital warts and a 75% reduction in the incidence of pre-cancerous lesions in the anus caused by the four strains against which the vaccine protects.

Who is the vaccine recommended for?

The vaccine is recommended for women and men aged 9 to 26 years.

Why at such a young age?

As I wrote because of the high prevalence of this virus infection immediately after the start of intercourse and on the other hand maximum efficacy that has been proven when the vaccine is given before intercourse.

In the United States the vaccine is routinely given at ages 11-12 years (girls and boys).

In Israel, the eighth grade was set as the age to be vaccinated.

What about people over the age of 27? You can of course also be vaccinated at these ages, but it is recommended to focus on those people / populations where there is a constant risk of exposure to the virus between them – a large amount of sexual contact, infection with another sexually transmitted disease, past sexual abuse, men having sex with men and more. It is recommended in this group to review the vaccination briefing and find out if the candidate meets one of the definitions for which there is a recommendation to be vaccinated.

And what if it is known that the girl / boy in the eighth grade will not have sex in the coming year? Is it worth the wait?

A correct question that is asked a lot. My personal opinion is that in eighth grade, even if the parents are sure that the boy / girl will not have sex soon, there is room for vaccination.

In previous years we waited for Gradsil 9, which was launched in other countries before arriving in his country. During this period it was frustrating to recommend in populations that need to be vaccinated against the (old) Gardasil vaccine that is why many of the parents who were confident that their child would not have sex in the coming year preferred to wait.

There is currently no better vaccine in hand, and I think there is room to vaccinate (for free and as part of the routine immunization program) all children.

Is it possible to vaccinate someone who is already having sex or has already been infected with the virus?

The answer is yes. Not everyone who have sex is infected, and even those who are infected may be infected with strains different from the vaccine strains so there is nothing to lose in vaccinating this population.

By the same token, it is also possible and desirable to vaccinate a population of appropriate ages that already have genital warts or pathological pap surfaces although the vaccine will no longer protect against those strains for which there has been exposure in the past.

Where is the vaccine given?

The vaccine is given intramuscularly, to the arm area.

Since when did vaccination begin to be a routine in the State of Israel and to whom?

School year 2013-2014 – Cervarix vaccine for girls only in eighth grade.

School year 2014-2015 – Gardasil 4 vaccine for girls only in eighth grade.

From the 2015-2016 school year to (including) the 2018-2019 school year – the Gradsil 4 vaccine for girls and boys in the eighth grade.

From the 2019-2020 school year – the Gradsil 9 vaccine will be given to girls and boys in the eighth grade.

Theoretically, the children should have been vaccinated with the number of doses required in the eighth grade of school (two doses at this age, see below).

How many servings do I need to get vaccinated?

Depending on the age of onset of the vaccine.

Girls and boys under the age of 15 (including those vaccinated in eighth grade) should receive two doses at least 5 months apart from the first dose to the second (if the second dose was given after less than five months from the second dose, then a third dose is required).

Children over the age of 15 should receive three servings. The minimum time interval between the first and the second dose is 4 weeks, the minimum time interval between the second and third dose is 12 weeks (and the minimum time interval between first and third dose is 16 weeks).

What does one do if he received one (or two) servings but did not complete the series?

An important rule in vaccines in general and in this vaccine in particular means that there is no need to start the series anew, but to continue giving the vaccine as soon as possible with reference to the minimum time interval between doses as described earlier.

For example, a 17.5-year-old girl who received a first and only dose before the age of 15 but has not received the second dose since and wants to get vaccinated. She should just complete the second dose soon and she will be considered vaccinated.

How can a parent know if their child is resilient?

You can only know by looking at the child’s immunization booklet. In light of the low response rate to the vaccine within the school, and in light of the fact that some children received only some of the doses, it is recommended that parents check with the vaccination book whether the child is properly vaccinated in the required number of doses.

What happens to children who have been vaccinated in a full series with the vaccines Gradsil or Cervrix but now have a new vaccine (Gradesil 9), should they be vaccinated again?

Those who have been vaccinated in the past in a full series do not need to be revaccinated, not even with the "new" vaccine.

Anyone who still wants to gain the extra protection provided by Gradsil 9, can do so for a fee according to the time intervals written in this indication in the vaccination guide.

What happens to children who have been vaccinated in a series that is not complete with the vaccines Gardasil or Cervrix but now there is a new vaccine (Gardasil 9), should the vaccines be supplemented with the new vaccine?

The supplement that is made to the vaccine series deserves to be given in the best vaccine currently on the market and is Gradsil 9, even if the previous doses have been given in other vaccines.

What is the expected duration of protection after this series of vaccines?

Since the first vaccine was marketed in 2006, then as of today (14 years later) it has been proven that the vaccine provides lasting protection for at least 14 years.

Long-term follow-up studies are ongoing to decide whether an additional impulse dose will be required later.

What are the side effects of the vaccine?

Common side effects that may occur after Gardasil vaccine are side effects at the injection site (pain, redness and swelling). Local effects are more common after Gradsil 9 vaccine compared to Gradsil.

From the day of receipt of the vaccine until 15 days after receiving it, headache, dizziness, general malaise, muscle / joint pain and abdominal pain have been reported.

Because of the fainting that was reported among adolescent girls who received the vaccine, it is recommended that this population be vaccinated while lying down.

I mention that in the eighth grade, the children are vaccinated as part of school with the triple vaccine (tetanus, diphtheria and pertusss). My recommendation is to vaccinate the two vaccines at different sites and not in one hand. Recalls that after a tetanus vaccine (especially for those who have had previous tetanus vaccines in the past) the arm hurts a little.

What about the reported autoimmune side effects?

In 2013, Professor Yehuda Sheinfeld, a rheumatologist at Sheba Hospital, published a number of cases of autoimmune symptoms occurring in close proximity to the papilloma vaccine. But a time relationship is not a causal relationship and even the authors of the articles in question concluded that long-term follow-up on a larger group of vaccinated people is required.

Happily, comprehensive studies conducted before and after 2013 demonstrate that there is no difference in the incidence of autoimmune symptoms in the vaccinated population compared to those without the vaccine.

In addition, in 2017 the World Health Organization declared papillomavirus vaccines the safest to use. This conclusion came after a systematic examination of all the studies conducted regarding the safety of vaccines and based on over 270 million doses of vaccines given so far worldwide.

Who can not get vaccinated?

People who have a known sensitivity to one of the components of the vaccine or who have developed an allergic reaction after receiving a previous dose of the vaccine.

What did I actually recommend?

I recommend the Gardasil 9 vaccine at the ages presented. I recommend getting the vaccine regularly for all of our eighth grade children.
Action speaks louder than words, Attaches a picture of my signature in the vaccination book of my first daughter after I vaccinated her with this vaccine.

Can and how can this vaccine be combined with other routine vaccines?

Gradsil 9 can be given with all the usual routine vaccines, including the triple vaccine (tetanus, diphtheria and pertussis) given routinely in the eighth grade. My recommendation is to vaccinate at two different sites (right hand and left hand).

What do those who have not received the vaccine at school and want to have it do?

Boys and girls are entitled to complete the vaccine free of charge until the 18th birthday at the offices of the Ministry of Health (it is necessary to call the offices to make an appointment to complete the vaccine at 5400 *).

Beyond this age, the Gardasil 9 vaccine is available for a fee at health funds and private pharmacies.

For men and women, Gardasil 9 is available in the army for a fee through a "doctor’s visit" after receiving a military prescription.

How much does the vaccine cost?

The full price of the Gardasil 9 vaccine is 688 NIS. However, the vaccine can be purchased at any of the health funds at a subsidized price, depending on the insured’s supplementary insurance.

Actually you need to go to the pediatrician / family / gynecologist, ask for a prescription for the vaccine and usually also an instruction for the nurse to vaccinate.

With the prescription to go to the pharmacy that works with the same HMO, buy the vaccine, arrange for it to be transferred as soon as possible with some ice to the nurse at the HMO and vaccinate (some HMOs also require a referral to a nurse from the doctor to administer the vaccine).

You should return to the doctor after receiving the first vaccine dose in order to get prescriptions for the additional vaccine doses in the series and go to purchase the doses and get vaccinated at the required intervals between vaccine doses as explained above.

Good luck!