HPV Frequently Asked Questions

Human papillomavirus vaccine Frequently Asked Questions for Health Professionals

 

What is HPV?

Human papillomavirus (HPV) is a double stranded DNA virus that infects squamous epithelia including the skin and mucous membranes of the upper respiratory and anogenital tracts. There are more than 100 different types of HPV, most of which are responsible for common skin warts (verrucae). Around 40 HPV types can infect the genital area, including the skin of the penis, vulva, and anus, and the linings of the vagina, cervix and rectum. Some of these are low‐risk types (e.g. HPV 6 and 11) which cause genital warts, while others are high‐risk (oncogenic) types.

Thirteen high-risk (oncogenic) HPV types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68) have been identified. Although most HPV infections are asymptomatic and self‐limiting, persistent infection with high-risk HPV types may cause cancers of the cervix, oropharynx, anus, vagina, vulva and penis.

The majority of HPV infections do not cause any symptoms and infection is usually cleared by the body’s own immune system without the need for other treatment. More than 90% of new HPV infections clear or become undetectable within 2 years. However, persistent infection with high‐risk oncogenic HPV types is the most important risk factor for HPV-related diseases including cancer precursors and invasive cervical cancer.

In Europe, HPV types 16 and 18 cause over 70% of cervical cancers, and HPV types 31, 33, 45, 52, and 58 are estimated to cause an additional 19% of cervical cancers. 

How is HPV spread?

Transmission of HPV can occur by skin to skin contact during vaginal, oral or anal sexual intercourse or genital contact with an infected person. Anyone who is sexually active can contract HPV. A person with HPV can pass the infection to someone else even when they have no signs or symptoms. Condom use reduces, but does not eliminate the risk of transmission of HPV.

What is the burden of HPV disease in Ireland?

HPV is reported to be responsible for approximately 1 in every 20 cases of cancer across the world. 

In Ireland, an average of 406 cancers are attributable to HPV infection in both women and men every year. Of these cases, 307 are attributable to HPV types 16 and 18 and a further 53 cases are attributable to HPV types 31, 33, 45, 52 and 58 (all HPV types targeted by Gardasil 9). The majority of these cancers are diagnosed in the cervix and oropharynx. HPV is also causative for many cancers of the anus, vulva, vagina and penis.

Of the 292 cervical cancers diagnosed annually, 260 (89%) are attributable to HPV strains targeted by Gardasil 9 vaccine.

Of 133 oropharyngeal squamous cell carcinomas, 51 (38%) are attributable to HPV strains targeted by Gardasil 9.

See Table 1 for more information

Table 1. Average annual number of HPVassociated cancer cases, 2010 2014 (Ireland) showing number of these cancers attributable to strains targeted by 9valent vaccine

Cancer site

HPV

**associated Cancers

Percentage of Total

Cancers

***attributable to HPV strains targeted by Gardasil 9 vaccine

Cervical

292

54%

260

Oropharyngeal *SCC

133

25%

51

Vulvar SCC

38

7%

6

Anal/Rectal SCC

36

7%

28

Penile SCC

32

6%

9

Vaginal SCC

10

2%

6

TOTAL

538

 

360

 

*SCC = squamous cell carcinoma

** A HPVassociated cancer is a specific cellular type of cancer that is diagnosed in a part of the body where HPV is often found. Three out of four of these cancers are diagnosed in women and one out of four in men.

***A HPVattributable cancer is a cancer where there is direct evidence the cancer is caused by HPV.

Data courtesy of Health Information and Quality Authority Health Technology Assessment (HTA) of extending the national immunisation schedule to include HPV vaccination of boys 2018.

Oncogenic HPV is also responsible for a range of other precancerous lesions of the cervix, vagina and vulva in women. Over 6,500 in situ (CIN 1, 2, 3) lesions of the cervix are diagnosed annually.

HPV Vaccine

What is HPV vaccine?

HPV vaccines contain virus‐like particles (VLPs) produced from the major capsid protein L1 of each HPV type using recombinant DNA technology.

These vaccines: 

  • contain no viral DNA and are not infectious or oncogenic
  • are not live vaccines
  • cannot cause HPV infection
  • cannot cause cancer.

What HPV vaccines are licensed?

The HPV vaccine currently used in Ireland is: 

  • Gardasil 9 (manufactured by MSD), a nonavalent vaccine containing VLPs (Virus-Like Particles) for nine HPV types (6, 11, 16, 18, 31, 33, 45, 52 and 58).

When did the HPV vaccination programme start in Ireland?

In September 2010 quadrivalent HPV vaccine (HPV4) was introduced for girls in second level school and age-equivalent girls in special schools and those educated at home. HPV4 vaccine was also offered to girls in second year or equivalent.

From 2011 to 2014, girls in sixth year of second level school or equivalent were offered HPV4 vaccine as part of a catch-up programme.

Following recommendations from the National Immunisation Advisory Committee (NIAC), the Minister for Health and Children introduced the nonavalent vaccine, Gardasil 9 (HPV9) into the national immunisation programme from September 2019 for all students in first year of second level school or equivalent as part of the national strategy to prevent cancers attributable to HPV.

Gardasil 9 is licensed for active immunisation of individuals from the age of 9 years against the following HPV diseases:

  • premalignant lesions and cancers affecting the cervix, vulva, vagina and anus caused by the constituent HPV types
  • genital warts (condyloma acuminata) causally related to the specific HPV types

As of March 2022, over 140 countries and territories give HPV vaccine as part of their national immunisation schedule, and more than 50 of them, including the US, UK and Australia have introduced gender-neutral HPV vaccination programmes.

Why is Gardasil 9 offered to boys?

HPV vaccination of boys provides direct protection against HPV‐related disease to boys.

On average, 538 cases of HPV-associated cancers were diagnosed per year in Ireland during the period 2010 to 2014. Of these, one out of four (145 or 27%) were in men and three out of four (393 or 73%) were in women.

Unlike cervical cancer precursors, there is no screening test available for oropharyngeal, anal or penile cancers in men. Though licensed for prevention of cancers of the female genital tract, anus and genital warts, with time it is expected that the Gardasil 9 vaccine will also be effective in reducing the incidence of other cancers attributable to HPV.

 

Vaccinating boys also provides greater protection to women

A gender-neutral programme reduces spread of HPV and is likely to reduce the overall burden of HPV related malignancy sooner than would a girls only programme.

 

A gender-neutral programme ensures that the vaccine programme is more robust

A gender-neutral programme ensures that the vaccine programme is more robust in relation to potential short‐term fluctuations in uptake.

 

Protection of vulnerable groups

Extension of the HPV vaccine programme to include boys will likely greatly improve protection against HPV infection and associated HPV‐attributable disease in vulnerable groups e.g. MSM and migrant groups.

How does Gardasil 9 work?

Gardasil 9 vaccination causes the mounting of the humoral immune response to develop antibodies to the antigens in the VLPs.

What are the constituents of Gardasil 9?

Virus like particles (VLPs) for HPV types

Other constituents:

  • Sodium chloride
  • L‐histidine
  • Polysorbate 80
  • Sodium borate
  • Water for injection
  • Adjuvant (substance that enhances an immune response)
  • Amorphous aluminium hydroxyphosphate sulphate (0.5mg Al)

Are there any reasons not to give the vaccine?

Contraindications 

  • Known anaphylaxis to the active substances, the adjuvant, or any of the vaccine constituents.
  • Pregnancy

Precautions

  • Acute severe febrile illness; defer until recovery.
  • Vaccine should be administered with caution to individuals with coagulation defects. For more information, please see the NIAC Chapter 2. General Immunisation Procedures
  • Syncope has been reported among adolescents before or following vaccination, particularly with the first dose. Recipients should be seated or lying down during vaccine administration.

When there are doubts as to whether or not to give a vaccine contact a Paediatrician or Consultant in Public Health Medicine.

How safe is the vaccine?

Gardasil 9 is safe and well tolerated.

 

On very rare occasions, a person may have a serious allergic reaction (anaphylaxis) to any vaccine, including HPV vaccines.

 

Other potential adverse reactions are listed below

Table 2: Adverse reactions following administration of Gardasil 9 occurring with a frequency of at least 1.0% from clinical trials

 

System Organ Class

Frequency

Adverse Reactions

 

Nervous system disorder

Very common

Headache

Common

Dizziness

Gastrointestinal disorders

Common

Nausea

General disorders and administration site conditions

 

Very Common

At the injection site: pain, swelling, erythema

Common

Pyrexia, fatigue,

At the injection site: pruritus, bruising

 

See SPC and PIL at https://www.hpra.ie/

 

Post marketing adverse events have also been reported, e.g. syncope (fainting); chills; malaise; vomiting.

Post‐vaccination fainting has been reported with most vaccines. Based on data from the USA, syncope is most common after three adolescent vaccines HPV, MCV4 (4th dose Meningococcal vaccine given in the USA), and Tdap. Vaccine recipients should be observed for at least 15 minutes after vaccination. If this is not practicable, vaccine recipients should wait in the vicinity for 15 minutes.

An EMA and a UK MHRA review found no evidence that HPV vaccines cause POTS.

 

Postural Orthostatic Tachycardia Syndrome (POTS) 

Postural Orthostatic Tachycardia Syndrome (POTS) is 4 times more common in females and onset peaks in adolescence. It is likely therefore to develop spontaneously in girls who are at the age when they have received HPV vaccine.

Worldwide independent health authorities have reviewed HPV vaccine safety and all have concluded that evidence does not support a link between HPV vaccine and the development of a range of chronic illnesses.

In January 2016, the EMA issued a final report on the review of HPV vaccines. This report found no evidence the vaccine was linked to complex regional pain syndrome (CRPS) or POTS. Please see link for full details at https://www.ema.europa.eu/en/documents/referral/hpv-vaccines-article-20-procedure-ema-confirms-evidence-does-not-support-they-cause-crps-pots_en.pdf

The European Commission endorsed the conclusion of the EMA.

The World Health Organization (WHO) Global Advisory Committee for Vaccine Safety (GACVS) has reviewed the evidence on the safety of Gardasil vaccine in 2007, and subsequently in 2008, 2009, 2013, 2014, 2015, 2017 and 2019. WHO has never reported safety concerns with HPV vaccines reporting in July 2017 that HPV vaccines are considered to be extremely safe.

Further information can be found at https://www.who.int/groups/global-advisory-committee-on-vaccine-safety/topics/human-papillomavirus-vaccines/safety

Why is Gardasil 9 recommended in 1st year of second level school?

NIAC recommends that HPV vaccine be given to 12-13 year old students (equivalent to first year of second level school) because:

  • The vaccine is most effective if given before sexual activity occurs
  • A superior immune response has been demonstrated at this age.

What is the NEW vaccine dose and schedule?

In November 2022, NIAC issued updated recommendations with respect to HPV vaccine dosage. The NIAC now recommend:

  • - A single dose schedule of HPV vaccine for all those aged 9 to 24 years of age.

 

  • - A two dose schedule of HPV vaccine at an interval of 0 and 6-12 months for those aged 25 years and older (up to the age of 45 years).

 If the second dose is given less than five months after the first dose, a third dose should be administered. This should be given 6–12 months after the first dose and at least 12 weeks after the incorrect second dose.

  • - Immunocompromised (for further information see the NIAC Chapter 10. Human Papillomavirus)

Those with the following conditions require a three dose schedule of HPV vaccine at 0, 2 and 6 months regardless of age.

  • Haematopoietic stem cell or solid organ transplant recipients
  • HIV infection
  • Malignant haematological disorders affecting the bone marrow or lymphatic systems, e.g., leukaemia, lymphomas, blood dyscrasias
  • Non-haematological malignant solid tumours
  • Primary immunodeficiency
  • Within two weeks of commencing, on or within three to six months of receiving significant immunosuppressive therapy* (for further information see NIAC Chapter 3)

 

For those with the above immunocompromising conditions, the three dose HPV vaccination schedule should be recommended by their treating Specialist/Consultant.  They can then either receive the vaccine as part of the national immunisation schedule or choose to pay for it privately.

 

*Advice from the NIAC for clinicians to aid in assessing whether their patient commencing, receiving, or post immunosuppressive therapy should receive 3 doses of HPV vaccine:

Ideally, recommended vaccines should be administered at least two weeks prior to commencing immunosuppressive therapy. Provided the HPV vaccine is administered two weeks or longer before starting immunosuppressive therapy, then the usual recommended dose schedule for age applies.

 

When considering vaccinating people who are about to start, are receiving or have received immunosuppressive therapy, it is important to review:

 

  • the mechanism of action of the treatment and duration of its effect on the immune system
  • the consequence of using combination therapies which can contribute to the nature, extent and length of the immunocompromising condition, e.g., corticosteroids with other immunosuppressive therapies such as disease-modifying anti-rheumatoid drugs
  • the anticipated duration of immunocompromise due to the disease or treatment
  • the underlying disease or condition
  • the interval since completing treatment

 

The degree of immunosuppression and the interval until immune reconstitution vary with the type and intensity of immunosuppressive therapy, radiation therapy, underlying disease, and other factors. Therefore, it may not be possible to make a definitive recommendation for an interval after cessation of immunosuppressive therapy when HPV vaccine can be administered effectively. Clinical assessment of each individual case is necessary to determine the likely degree and duration of immunosuppression.

Following clinical assessment by the specialist treating physician, seek further expert advice from an Immunologist if needed.

 

Immunosuppression may occur in the following (the lists are not exhaustive):

Those who are receiving or have received in the previous six months Immunosuppressive therapy for a solid organ transplant
Immunosuppressive chemotherapy or radiotherapy for any indication
Rituximab
Those who are receiving or have received in the previous three months  Targeted therapy for autoimmune disease e.g.,
  • JAK inhibitors
  • Biologic immune modulators including:
    • B-cell targeted therapies
    • monoclonal tumour necrosis factor inhibitors (TNFi)
    • T-cell co-stimulation modulators
    • soluble TNF receptors
    • interleukin (IL)-1, IL-6, IL-17/23 inhibitors

Non-biological oral immune modulating drugs e.g.,

  • methotrexate > 0.4 mg/kg/week
  • azathioprine >3.0mg/kg/day
  • 6-mercaptopurine >1.5mg/kg/day
  • mycophenolate >1g/day

Certain combination therapies at individual doses lower than stated above, including:

  • on prednisolone ≥7.5 mg per day with other immunosuppressants (other than hydroxychloroquine or sulfasalazine)
  • methotrexate (any dose) with leflunomide
Those who are receiving high dose corticosteroids

 Prednisolone or its equivalent:
Adults and children weighing ≥10kg:

  • ≥40mg/day for more than one week,
    or
  • ≥20mg/day for two weeks or longer

Children <10 kg:

  • 2 mg/kg/day for two weeks or longer

Why is the vaccine schedule changed to one dose for those aged 9 to 24 years of age?

The NIAC advise there is now sufficient evidence that there is no significant difference in vaccine effectiveness between those aged nine to 24 years of age who are immunocompetent who receive one, two, or three vaccine doses.

See the NIAC recommendations to the Department of Health from September 2022

See updated NIAC Chapter 10. Human papillomavirus, November 2022 for further information

What protection is provided by one dose?

In April 2022, the WHO Strategic Advisory Group of Experts on Immunization (SAGE) evaluated the evidence that has been emerging over past years that single-dose HPV vaccine schedules provide comparable efficacy to the two or three-dose regimens.

SAGE’s review concluded that a single-dose Human Papillomavirus (HPV) vaccine delivers solid protection against HPV, the virus that causes cervical cancer, that is comparable to 2-dose schedules.

For more information, please visit the WHO website 

What about students who received one dose of HPV vaccine during 2021/2022 school year?

An advisory note will be made available for parents to inform them that their child only now requires one dose of HPV vaccine in early 2023. If they have a weak immune system they may require three doses (as above).

It is however very important that these students still receive MenACWY vaccine.

What about students who received one HPV vaccine during 2022/2023 school year?

The NIACs new recommendation for one dose of HPV vaccine will not require a formal withdrawal of consent. A correspondence is being sent by the NIO, notifying all parents of those currently in first year about this new NIAC recommendation.

Can other vaccines be given at or around the same time?

Gardasil 9 vaccine can be administered at the same time as, or at any interval before or after any other vaccines such as Tdap (tetanus, low dose diphtheria and low dose acellular pertussis vaccine) and MenACWY vaccine (meningococcal vaccine).

What happens if a first year student is absent from school and misses their HPV vaccine dose (offered as part of the routine national immunisation schedule)?

The student should be given one appointment for a mop‐up clinic to be held at the end of the period of school vaccination clinics.  No further appointments are necessary unless student makes contact advising they are unable to attend the mop up clinic.

What about older students who wish to be vaccinated?

The Laura Brennan HPV Catch-Up Vaccination Programme will be available until the end of December 2023. This catch-up programme will provide a once only opportunity for those who were previously eligible for HPV vaccination and did not receive it, to be vaccinated. Those eligible for vaccination under the Laura Brennan HPV Catch-Up Vaccination Programme are:

  • Females (currently in 2nd year – 6th year of secondary school, or in age-equivalent special schools or educated at home) who have not received the HPV vaccine
  • Males (currently in 2nd year – 4th year of secondary school/5th year if they did not do transition year, or in age-equivalent special schools or educated at home) who have not received the HPV vaccine i.e. boys who were in 1st year from 1st September 2019 when the HPV vaccination programme was first extended to boys 
  • Unvaccinated females who have left second level education and are under 25 years of age on the date of vaccination

Please note:

  • Older boys, who were not eligible when the programme was extended to boys (outside of the above listed groups) are not included in the Laura Brennan HPV Catch-up Vaccination Programme and will need to source the HPV vaccine privately should they wish to receive it.
  • HPV vaccination is available for MSM aged ≤45 years in GUM clinics.

 

If a parent/legal guardian/individual seeking HPV vaccination makes contact with the vaccination team about the Laura Brennan HPV Catch-up Vaccination Programme they should be advised to visit www.hpv.ie for more information and to register their interest in the programme.

What about girls who request the HPV vaccine as part of the Laura Brennan HPV Catch-Up Vaccination Programme but who have already completed the HPV4 (Gardasil) vaccination schedule?

Girls who have completed the schedule with Gardasil do not need to be revaccinated with Gardasil 9.

What educational materials are available to vaccinators administering HPV vaccine?

Essential training for vaccinators is available on:

How effective is Gardasil 9?

  • Gardasil 9 is as effective as Gardasil for the prevention of diseases caused by the four shared HPV types (6, 11, 16, and 18), based on similar antibody responses in participants in clinical studies.
  • The trials that led to approval of Gardasil 9 found it to be nearly 100% effective in preventing many of the diseases caused by the five additional HPV types (31, 33, 45, 52, and 58) that it targets.

How long does protection last?

Following one, two or three vaccine doses, HPV antibodies reach an early peak followed by a decline to plateau around 18-36 months, and remain stable for at least 11 years.

HPV vaccination is effective in cervical cancer prevention.

A study from England observed a substantial reduction in cervical cancer and incidence of CIN3 (severe cervical abnormality) in young women after the introduction of the HPV immunisation programme in England, especially in individuals who were offered the vaccine at age 12–13 years.

Advising “the HPV immunisation programme has successfully almost eliminated cervical cancer in women born since Sept 1, 1995”

Lancet November 2021 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02178-4/fulltext

Among Swedish girls and women aged 10 to 30 years old, quadrivalent HPV vaccination (Gardasil vaccine which protects against 70% of cervical cancers) was associated with a substantially reduced risk of invasive cervical cancer at the population level.

In the study from Sweden cervical cancer was diagnosed in 19 women who had received the Gardasil vaccine and in 538 women who had not received the vaccine.

N Engl J Med 2020; https://www.nejm.org/doi/10.1056/NEJMoa1917338

How do I report an adverse event following vaccination?

All adverse events should be reported to the HPRA

What should happen with a student/individual who has a non-anaphylactic allergic reaction post vaccination?

The Immunisation Guidelines for Ireland state that those who have had a non‐ anaphylactic allergy may be given a subsequent dose(s) of that vaccine if indicated. 

The NIAC wish to draw attention to the following: 

  1. There are degrees of severity of hypersensitivity reactions.
  2. The only absolute contraindication to most vaccines is previous anaphylaxis to the vaccine or any of its constituents.
  3. Cases of hypersensitivity need to be considered on a case by case basis.
  4. Mild hypersensitivity reactions are not contraindications to a subsequent dose of a vaccine.
  5. More severe non-anaphylactic reactions should be discussed with a Consultant in Public Health Medicine and/or Paediatrician. In these cases, vaccination in a hospital setting may be appropriate.
  6. Recommendations from the NIAC, including those in the Immunisation Guidelines for Ireland, may differ from those of the SmPC and the Health Products Regulatory Authority (HPRA).

To assist in the assessment of reactions it is important that the HPRA adverse reaction report form is completed in full for all cases. A medication error does not need to be routinely reported to the HPRA unless the student experiences harm (i.e. an adverse reaction) associated with it. In any such cases involving adverse reactions, an adverse reaction report should be submitted to the HPRA, including information on the nature of the error involved.

Is Gardasil 9 contraindicated in immunosuppressed students?

No. Gardasil 9 is NOT contraindicated in students who are immunosuppressed as long as they are well and do not have a high fever. There is no risk to receiving HPV vaccine if their immune system is compromised – however the vaccine manufacturer has stated that those with reduced immune responses may not respond to HPV vaccine as well as those with healthy immune systems (this is the same as with most other vaccines). If the immunosuppression is expected to be temporary, vaccination may be deferred until the immune system is functioning normally i.e. 6 months after completion of standard‐dose chemotherapy for a malignancy. Please see The NIAC Chapter 3. Immunisation of Immunocompromised Persons for more information

For certain categories of immunosuppressed individuals, the NIAC recommend 3 doses of HPV vaccine, regardless of age. Please see answer to the FAQ ‘What is the new vaccine dose and schedule?’ above and the updated NIAC Chapter 10. Human papillomavirus for further information. 

Can Gardasil 9 be administered during pregnancy?

No. Gardasil 9 is not currently recommended during pregnancy, although there is no known risk associated with using recombinant vaccines during pregnancy.

What should happen if a female finds out she is pregnant and has received the vaccine?

If a female who was vaccinated subsequently finds out that she was pregnant at/or conceived around, the time of vaccination, any further HPV vaccination should be postponed. There is no evidence to date that the HPV vaccine will have caused any harm to her, the pregnancy, or the foetus. She should be advised to discuss the matter with her GP. The course of Gardasil 9 HPV vaccination may be finished when the pregnancy is completed if further doses are required.

Can Gardasil 9 affect fertility?

No. Gardasil 9 does not affect future fertility. 

See links to the U.S Centers for Disease Control and Prevention (CDC) information:

Do fully vaccinated girls need cervical screening?

Yes. Currently HPV vaccines only protect against HPV types which cause approximately 90% of cervical cancers. Girls who have been fully vaccinated still need to be screened for cervical cancer caused by the remaining HPV types which the vaccine does not protect against. In addition a small number of girls may not develop an adequate immune response post vaccination and a small number of girls may be already infected with HPV. Thus, it is essential that girls participate in the National Cervical Screening Programme when they are of an appropriate age.

 

 

This page was added on 6 December 2022