BMJ 2017;357:j2730 doi: 10.1136/bmj.
j2730 (Published 2017 June 22)
Practice
10 MINUTE CONSULTATION
Discussing human papilloma virus vaccination
1 2
Yan Ling Quah resident physician , Ieera Madan Aggarwal consultant
1
Singhealth Polyclinics, Singapore; 2Department of Gynaecological Oncology, KK Womens and Children's Hospital, Singapore
A mother and her 15 year old daughter come to your clinic. The
mothers other daughter, who is 12 years old, recently received
the human papilloma virus (HPV) vaccine at school. The mother
wants to know whether her 15 year old daughter who missed
her HPV vaccination should receive it now.
HPV is sexually transmitted. Infection is often asymptomatic.
In some people, however, HPV infection persists and over time
leads to genital warts or cancer, mainly cervical, but also anal,
penile, oral, and throat cancers (fig 1). The HPV types 16 and
18 together cause 70% of cervical cancers.1-4
Prophylactic vaccines against HPV are offered as part of the
national immunisation programme in many countries including
in the UK.1 These vaccines generate HPV-specific antibodies
that bind to the virus and prevent cervical infection. Table 1
shows the three types of vaccines available.
Vaccination coverage globally has been variable. Surveys among
parents find that the most common reasons for not vaccinating
their child include lack of knowledge about the vaccine, a belief
that it is not needed, their child is not sexually active, and
concerns about safety.6-8 A healthcare providers
recommendation is an important factor in parents decision to
vaccinate their child.9
What you should cover
Initiate a discussion about HPV
Explore whether the patient or their parents have heard of HPV
vaccination and what they know about it. You may ask about
the source of their information, whether they have considered
vaccination, and any concerns they have.
Explain the effects of vaccination
In large randomised controlled trials, both Cervarix and Gardasil
vaccines have been shown to be over 99% effective in
preventing precancerous lesions associated with HPV types 16
or 18 in young women with no evidence of previous
infection.10-12 Gardasil was additionally 96-100% effective in
preventing anogenital warts.10
Correspondence to: I M Aggarwal Ieera.aggarwal@singhealth.com.sg
This is part of a series of occasional articles on common problems in primary care. The BMJ welcomes contributions from GPs.
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PRACTICE
Antibody titres after vaccination are relatively high. A long term
follow-up study demonstrated that efficacy of the bivalent
vaccine Cervarix after 9.4 years was 95.6% against HPV types
16 and 18.13 For the quadrivalent Gardasil, no cases of
precancerous lesions or genital warts related to HPV 6, 11, 16,
or 18 were detected at five years follow-up.13 Longer term
studies are needed to establish if booster doses are required.
These trials measured antibody titres as the primary endpoint,
which is a surrogate marker for protection against cancer and
precancerous lesions. Evidence on long term immunogenicity
and prevention of cervical cancer is not available. Explain to
patients and their parents that, although the vaccine has been
shown to prevent infection with oncogenic HPV viruses, it is
not a replacement for routine adult cervical screening.14
Who may be vaccinated
HPV immunisation is usually recommended in adolescent girls
before onset of sexual activity, typically in the age group of
9-14 years. See table 2 for country-specific recommendations
regarding age and vaccination schedule.
All girls aged 12-13 years in the UK are offered the quadrivalent
vaccine Gardasil in school as part of the NHS childhood
immunisation programme.10 Girls who have missed vaccination
can be offered a catch-up vaccination up to 18 years of age.16
Vaccination for women over 18 years old is not covered by the
national programme in the UK, though some countries offer
vaccination up to 26 years of age.2 The effects of vaccination
in women over this age group have not been sufficiently studied.
Some countries, including the United States, Canada, and
Australia, also offer vaccination to adolescent boys to prevent
HPV related anal and oropharyngeal cancers. Routine
vaccination is currently not offered to males in the UK. The
effectiveness and feasibility of immunisation of adolescent boys
and of men who have sex with men is being studied.17-19
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BMJ 2017;357:j2730 doi: 10.1136/bmj.j2730 (Published 2017 June 22)
What you need to know
HPV vaccination protects against infection with oncogenic human papilloma viruses responsible for up to 70% of all cervical cancers
Offer vaccination to adolescent girls in line with the recommended schedule in your country
Explain that vaccination is not a substitute for routine cervical screening, which continues to be an important strategy for prevention
of cervical cancer
Inform about the vaccination schedule for
HPV
Refer to national guidelines in planning the vaccination schedule
for your patient. Initially, the HPV vaccine was given as three
doses (at 0, 2, and 6 months), but recent randomised controlled
trials show that it is as effective when given in two doses (0 and
6 months) in 9-14 year olds because younger adolescents mount
a higher immune response.6 20 The vaccine is administered as
intramuscular injections at least six months (and no longer than
two years) apart.7 8 From the age of 15 years, patients should
receive the three dose course.21 The age of starting the
vaccination governs the schedule.
Explain the safety profile of the vaccine
You may highlight to parents that the HPV vaccines contain
virus-like particles without any viral DNA and hence are
non-infectious. The World Health Organization Global Advisory
Committee for Vaccine Safety (GACVS) regularly reviews
evidence on safety of HPV vaccines and concluded that both
HPV vaccines are safe and that potential benefits outweigh any
harms.22
Commonly reported adverse effects include injection site
reactions (pain, swelling, redness), nausea, headache, fever,
muscle or joint pain, and syncope.22-24 Syncope is commonly
attributed to vagal nerve stimulation, and the risk can be reduced
by a 15 minute post-vaccination observation with patients seated
or lying down. As with other vaccines, an anaphylactic reaction
after HPV vaccination is a contraindication for a subsequent
dose.
Suspected cases of complex regional pain syndrome after HPV
vaccination were reported in the UK and Japan, which led to
suspension of HPV vaccine recommendations in Japan in 2013.
In December 2012, the UK Medicines and Healthcare products
Regulatory Agency (MHRA) published a safety assessment
report that concluded there was insufficient evidence of a causal
association with the HPV vaccine.9 25 This was backed by reports
in 2013 and 2014 by the GACVS and the European Medicines
Agency.26 27
What you should do
Offer vaccination as per the recommended immunisation
schedule in your country based on the patients age. This vaccine
is supplied free of cost in the NHS. In countries where the
vaccine is not offered as part of a national programme, local
costs and availability must be discussed.
Reinforce that vaccination is not a substitute for routine cervical
cancer screening as it does not protect against all HPV
subtypes.3 4 About 30% of cervical cancer cases are caused by
HPV subtypes not covered by the vaccine. Regular cervical
smears are still important for early detection and treatment of
pre-invasive cervical abnormalities.
Report any side effects on administration of the vaccine, as
safety of the vaccine is continuously being monitored. In the
UK, the MHRA collects data on vaccine safety via the Yellow
Card Scheme, where anyone can report a suspected side effect.22
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Page 2 of 7
PRACTICE
You may explain safe sex practices if the patient inquires about
ways to minimise risk of infection and cancer.
We thank Chung Sze Ryn and Lim Yu Hui for helping us with the
diagram regarding the sequelae of HPV infection and preventive
strategies.
We have read and understood BMJ policy on declaration of interests
and declare that we have no relevant interests to declare.
1 Bruni L, Barrionuevo-Rosas L, Albero G, et al. Human papillomavirus and related diseases
in the world. ICO Information Centre on HPV and Cancer, 2015.
2 Centers for Disease Control and Prevention. HPV Vaccine Information for Clinicians- Fact
Sheet. 2012. www.cdc.gov/std/hpv/stdfact-hpv-vaccine-hcp.htm.
3 Kitchener HC, Denton K, Soldan K, Crosbie EJ. Developing role of HPV in cervical cancer
prevention. BMJ 2013;357:f4781. doi:10.1136/bmj.f4781 pmid:23926316.
4 Stillo M, Carrillo Santisteve P, Lopalco PL. Safety of human papillomavirus vaccines: a
review. Expert Opin Drug Saf 2015;357:697-712. doi:10.1517/14740338.2015.
1013532 pmid:25689872.
5 Joura EA, Giuliano AR, Iversen OE, et al. Broad Spectrum HPV Vaccine Study. A 9-valent
HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med
2015;357:711-23. doi:10.1056/NEJMoa1405044 pmid:25693011.
6 Kamerow D. HPV vaccine: effective but underused in the US. BMJ 2016;357:i2060. doi:
10.1136/bmj.i2060 pmid:27081105.
7 McCarthy M. US falls short of target for vaccinating adolescents against HPV. BMJ
2014;357:g4877. doi:10.1136/bmj.g4877 pmid:25069751.
8 Dobson SR, McNeil S, Dionne M, et al. Immunogenicity of 2 doses of HPV vaccine in
younger adolescents vs 3 doses in young women: a randomized clinical trial. JAMA
2013;357:1793-802. doi:10.1001/jama.2013.1625 pmid:23632723.
9 Rambout L, Hopkins L, Hutton B, Fergusson D. Prophylactic vaccination against human
papillomavirus infection and disease in women: a systematic review of randomized
controlled trials. CMAJ 2007;357:469-79. doi:10.1503/cmaj.070948 pmid:17671238.
10 Centers for Disease Control and Prevention. Human papillomavirus (HPV) vaccine safety.
CDC, 2015. www.cdc.gov/vaccinesafety/vaccines/hpv-vaccine.html.
11 Garland SM, Hernandez-Avila M, Wheeler CM, et al. Females United to Unilaterally
Reduce Endo/Ectocervical Disease (FUTURE) I Investigators. Quadrivalent vaccine
against human papillomavirus to prevent anogenital diseases. N Engl J Med
2007;357:1928-43. doi:10.1056/NEJMoa061760 pmid:17494926.
12 FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent
high-grade cervical lesions. N Engl J Med 2007;357:1915-27. doi:10.1056/
NEJMoa061741 pmid:17494925.
13 De Vincenzo R, Conte C, Ricci C, Scambia G, Capelli G. Long-term efficacy and safety
of human papillomavirus vaccination. Int J Womens Health 2014;357:999-1010. doi:10.
2147/IJWH.S50365 pmid:25587221.
14 World Health Organization, International Agency for Research on Cancer. Primary
end-points for prophylactic HPV vaccine trials. IARC Working Group Report vol 7. IARC,
2013.
15 Hanley SJB, Yoshioka E, Ito Y, Kishi R. HPV vaccination crisis in Japan. Lancet
2015;357:2571. doi:10.1016/S0140-6736(15)61152-7 pmid:26122153.
16 Public Health England. Human papillomavirus (HPV): the green book, chapter 18a. 2014.
www.gov.uk/government/publications/human-papillomavirus-hpv-the-green-book-chapter-
18a.
17 Mariani L, Venuti A. HPV vaccine: an overview of immune response, clinical protection,
and new approaches for the future. J Transl Med 2010;357:105. doi:10.1186/1479-5876-
8-105 pmid:20979636.
18 Stanley M. HPV vaccination in boys and men. Hum Vaccin Immunother 2014;357:2109-11.
doi:10.4161/hv.29137 pmid:25424825.
19 Stanley M, OMahony C, Barton S. HPV vaccination. BMJ 2014;357:g4783. doi:10.1136/
bmj.g4783 pmid:25073784.
20 Kreimer AR, Struyf F, Del Rosario-Raymundo MR, et al. Costa Rica Vaccine Trial Study
Group Authors PATRICIA Study Group Authors HPV PATRICIA Principal
Investigators/Co-Principal Investigator Collaborators GSK Vaccines Clinical Study Support
Group. Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine:
combined analysis of data from the Costa Rica Vaccine and PATRICIA Trials. Lancet
Oncol 2015;357:775-86. doi:10.1016/S1470-2045(15)00047-9 pmid:26071347.
21 European Medicines Agency. PRAC recommendations on signals. Adopted at the PRAC
meeting of 7-10 April 2014. www.ema.europa.eu/docs/en_GB/document_library/PRAC_
recommendation_on_signal/2014/04/WC500165809.pdf.
22 Holman DM, Benard V, Roland KB, Watson M, Liddon N, Stokley S. Barriers to human
papillomavirus vaccination among US adolescents: a systematic review of the literature.
JAMA Pediatr 2014;357:76-82. doi:10.1001/jamapediatrics.2013.2752 pmid:24276343.
23 Villa LL, Ault KA, Giuliano AR, et al. Immunologic responses following administration of
a vaccine targeting human papillomavirus Types 6, 11, 16, and 18. Vaccine
2006;357:5571-83. doi:10.1016/j.vaccine.2006.04.068 pmid:16753240.
24 World Health Organization. Human papillomavirus vaccines: WHO position paper, October
2014. Wkly Epidemiol Rec 2014;357:465-91.pmid:25346960.
25 Huygen F, Verschueren K, McCabe C, et al. Investigating reports of complex regional
pain syndrome: an analysis of HPV-16/18-adjuvanted vaccine post-licensure data.
EBioMedicine 2015;357:1114-21. doi:10.1016/j.ebiom.2015.07.003 pmid:26501109.
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BMJ 2017;357:j2730 doi: 10.1136/bmj.j2730 (Published 2017 June 22) Page 3 of 7

PRACTICE

Further educational resources

Resources for patients
Public Health England. Immunisation: human papillomavirus (hpv). www.gov.uk/government/collections/immunisation#human-
papillomavirus-(hpv)
NHS Choices. Vaccinations: HPV vaccine. www.nhs.uk/conditions/vaccinations/pages/hpv-human-papillomavirus-vaccine.aspx

Resources for clinicians

Public Health England. Human papillomavirus (HPV): the green book, chapter 18a. www.gov.uk/government/uploads/system/uploads/
attachment_data/file/317821/Green_Book_Chapter_18a.pdf
Centers for Disease Control and Prevention. Human Papillomavirus (HPV). www.cdc.gov/hpv/hcp/index.html

Education into practice

When was the last time you brought up a discussion with a patient regarding vaccination against HPV?
While discussing HPV vaccination with young girls, would you also discuss safe sex practices?
Are you familiar with the HPV vaccination schedule in your country?

How patients were involved in the creation of this article

In the process of writing this article, we asked around 50 teenage girls, most of whom were yet to receive the vaccine, and their mothers
regarding their understanding of HPV vaccination. We noted lack of awareness about the indication for this vaccine, its potential benefits
and adverse effects. A patient reviewed this article and emphasised adding information on adverse effects of the vaccine since that is often
a major concern among parents.

26 MHRA. Cervarix HPV vaccine: safety update at end of 4 years routine use in HPV Published by the BMJ Publishing Group Limited. For permission to use (where not already
immunisation programme. 2012. www.mhra.gov.uk/safety-public-assessment-reports/ granted under a licence) please go to http://group.bmj.com/group/rights-licensing/
CON221607.
permissions
27 Global Advisory Committee on Vaccine Safety, 1213 June 2013. Wkly Epidemiol Rec
2013;357:301-12.pmid:23909011.

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BMJ 2017;357:j2730 doi: 10.1136/bmj.j2730 (Published 2017 June 22) Page 4 of 7

PRACTICE

Tables

Table 1| Types of HPV vaccines2

Vaccine Type Protection against HPV types Licensed for use

Cervarix Bivalent Types 16, 18 (associated with cervical cancer) Females aged 10-25 years
Gardasil Quadrivalent Types 6, 11 (associated with anogenital warts) Females and males aged 9-26 years
Types 16, 18 (associated with cervical cancer)
Gardasil 9 Nonavalent Types 6, 11 (associated with anogenital warts) Females and males aged 9-26 years
Types 16, 18 (associated with cervical cancer)
Types 31, 33, 45, 52, 58 (responsible for ~14% of HPV associated cancers in women and ~4%
of HPV associated cancers in men5)

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PRACTICE

Table 2| Recommended HPV vaccination age and dose schedules of various countries

Vaccine type Target age group Dose schedule Special comments

Australia (www.hpvvaccine.org.au)
Quadrivalent Girls and boys 12-13 years old 3 doses (0, 2, 6 months) Used in school-based national HPV
vaccination programme
Austria (www.hpvcentre.net/statistics/reports/AUT.pdf)
Quadrivalent Girls and boys 9 years old 2 doses (0, 6 months) National vaccination programme
Canada (www.immunizebc.ca/diseases-vaccinations/hpv)
Bivalent Girls 9-14 years old 2 doses (0,6 months)
Girls 15-<27 years old 3 doses (0,1,6 months)
Women 27 years old with high risk
Quadrivalent Girls and boys 9-13 years old 2 doses (0, 6 months or 0, 12 months)
Girls and boys 14-<27 years old 3 doses (0, 2, 6 months)
Women and men 27 years old with high risk
MSM <27 years old
Nonavalent Girls and boys 9-<27 years old 3 doses (0,2,6 months)
Women and men 27 years old with high risk
MSM <27 years old
Denmark (www.ssi.dk/English/PublicHealth/Vaccination/The%20Danish%20Childhood%20Vaccination%20Programme/Q%20and%20A/HPV%20Vaccination.
aspx)
Bivalent Girls 12-13 years old 2 doses (0, 6 months) Part of childhood immunisation
programme
Grils 14-18 years old 3 doses (0,2,6 months)
Hong Kong (www.cervicalscreening.gov.hk/english/hum/hum_ccv.html)
Bivalent Girls 9-14 years old 2 doses (0, 6 months)
Girls 15 years old 3 doses (0, 1, 6 months)
Quadrivalent Girls and boys 9-13 years old 2 doses (0, 6 months)
Girls and boys 14 years old 3 doses (0, 2, 6 months)
Nonavalent Girls and boys 9-14 years old 2 doses
Girls and boys 15 years old and above 3 doses
Japan (government withdrew recommendation for HPV vaccine in 2013 due to controversies15)
Korea (www.hpvcentre.net/statistics/reports/KOR.pdf)
Bivalent Girls 11-12 years old 3 doses (0, 1, 6 months) Part of national immunisation
programme
Girls 9-14 years old (alternative) 2 does (0, 6 months)
Quadrivalent Girls 11-12 years old 3 doses (0, 2, 6 months)
Girls 9-13 years old (alternative) 2 doses (0, 6 months)
Malaysia (www.myhealth.gov.my/en/immunisation-schedule/)
Quadrivalent Girls 13 years old 2 doses (0, 6 months) Part of national HPV immunisation
programme
Singapore (www.healthhub.sg/live-healthy/312/HPV_immunisation_FAQ)
Bivalent Girls 9-13 years old 2 doses (0, 6 months)
Girls 14- 25 years old 3 doses (0, 1, 6 months)
Quadrivalent Girls 9-13 years old 2 doses (0, 6 months)
Girls 14-26 years old 3 doses (0, 2, 6 months)
South Africa (www.hpvcentre.net/statistics/reports/ZAF.pdf)
Bivalent Girls 9-14 years old 2 doses (0, 5-7 months)
Girls 15 years old and above 3 doses (0, 1, 6 months)
Quadrivalent Girls and boys 9-13 years old 2 doses (0, 6 months)
Girls and boys 14 years old and above 3 doses (0, 2, 6 months)
Sweden, www.norrbotten.se/upload/pv/stpv/HPV-vaccination/Vaccination_blad_HPV_foraldrar_engelska.pdf
Quadrivalent Girls 10-12 years old 3 doses (0, 2, 6 months) Part of national school-based
vaccination programme
Taiwan (http://shmc.osa.ntu.edu.tw/en/policlinic/policlinic4)

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PRACTICE

Table 2 (continued)

Vaccine type Target age group Dose schedule Special comments

Bivalent Girls 10-25 years old 3 doses (0, 1, 6 months)
Quadrivalent Girls 9-26 years old 3 doses (0, 2, 6 months)
UK (www.nhs.uk/Conditions/vaccinations/Pages/hpv-human-papillomavirus-vaccine.aspx)
Quadrivalent Girls 12-13 years old 2 doses (0, 6 months) For girls 12-13 years old, part of
NHS childhood vaccination
Girls 15 years old 3 doses (0, 2, 6 months)
programme
US (www.cdc.gov/hpv/hcp/index.html)
Quadrivalent and nonavalent Girls and boys 11-12 years old 2 doses (6-12 months apart) or 3 doses (0, 2, If 2 doses <5 months apart, 3rd dose
Girls and boys 15 years old 6 months) to be given
11-12 years is recommended age of
vaccination

MSM = Men who have sex with men.

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PRACTICE

Figure

Fig 1 Sequelae of HPV infection and preventive strategies

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