Evidence To Recommendation Table 1 Dose Vs 2 Dose
Evidence To Recommendation Table 1 Dose Vs 2 Dose
Evidence To Recommendation Table 1 Dose Vs 2 Dose
Question: Should an off label2, permissive one dose HPV vaccine schedule for use in the routine and/or multi-age cohort (MAC)
catch up strategies be recommended?
Population: Main population is pre-adolescent and adolescent girls (9-14 years old), but boys and older adults are also included.
Intervention: Single dose vaccination; bivalent (Cervarix and Cecolin), quadrivalent (Gardasil), and nonavalent vaccines (Gardasil 9).
Comparison(s): 2 doses of HPV vaccination
Outcome:
Clinical outcome: including, but not limited to invasive cervical, vaginal, vulval, anal, penile or head and neck cancer; cervical
intraepithelial neoplasia (CIN) grade 3+; CIN2+; histological and cytological abnormalities; anogenital warts; high risk HPV infection
(genotype-specific prevalence, incidence and/or persistence)
Immunological outcome; seroconversion or seropositivity; geometric mean titers (GMT) of HPV antibodies
Background: As of March 2022, 117 countries introduced HPV vaccine in their national immunization schedules, but these countries
represent only a third of the global population of girls and 40% of the global burden of cervical cancer.
In October 2019, SAGE reviewed the evidence on a single dose of HPV vaccines to protect 9-14-year-old girls, the primary target
population, against cervical cancer. SAGE concluded the quality and amount of evidence was insufficient for this policy decision and
that the evidence from the purposefully designed single dose randomized control trials (RCTs) was required to inform policy
decisions. Several of the RCTs and effectiveness studies designed to assess single dose schedules have started to generate interim
results during 2021.
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This Evidence to Recommendation table is based on the DECIDE Work Package 5: Strategies for communicating evidence to inform decisions about health system and public health interventions.
Evidence to a recommendation (for use by a guideline panel). http://www.decide-collaboration.eu/WP5/Strategies/Framework
2
The recommendations contained in this publication are based on the advice of independent experts, who have considered the be st available evidence, a risk–benefit analysis and other factors, as
appropriate. This publication may include recommendations on the use of medicinal products for an indication, in a dosage form, dose regimen, population or other use parameters that are not
included in the approved labelling. Relevant stakeholders should familiarize themselves with applicable national legal and ethical requirements. WHO does not accept any liability for the procurement,
distribution and/or administration of any product for any use.
1
In November 2020, the World Health Assembly adopted the Global Strategy towards the elimination of cervical cancer. The strategy
calls on each country to introduce HPV vaccination by 2030 and set a target of 90% of girls fully vaccinated with HPV vaccine by age
of 15. HPV vaccine coverages are below the target of 90% in the majority of countries and the observed high drop out between the
first and the second dose indicate programmatic challenges.
Programmatic challenges to introducing the vaccine include high cost and supply constraints. The latter have affected in particular
Low and Middle income countries since 2018 and led to delayed introductions and delayed or canceled multi age cohort catch up
strategies in GAVI eligible countries.
2
genital warts. BMC Infectious Diseases,
2013;13:39)
Benefits of the Recent data show that single dose HPV vaccine
Un-
intervention No Yes Varies is highly efficacious (VE > 95%) in a RCT among
certain
15 to 20 year old population (Kenshe RCT,
Are the Barnabas et al. 2021), and showed similar
efficacy compared to 2 or 3 doses of HPV
desirable
vaccine in 10-18 year old girls in a post RCT
BENEFITS & HARMS OF THE OPTIONS
anticipated
follow up study (IARC India, 2021, Basu et al.
effects large? 2021).
3
Future improvements in quality and coverage
of cervical cancer screening and treatment
programmes may mitigate any lower
protection from a single dose.
4
Favours Favours
Balance inter- com-
Favours Favours
Unclear
The benefits of protection against all HPV
both neither
between vention parison related diseases, cervical but also other forms
benefits and of cancers and genital warts, outweigh any
harms ☐ ☐ ☒ ☐ ☐
harm that may arise from vaccination (e.g.,
pain during immunization, AEFIs)
What is the Effectiveness of the intervention As per the Grade table (attached)
overall quality No
Very Mod- The quality of evidence on non-inferiority (1 vs
included Low High
of this studies low erate 2 doses (IARC India post RCT follow up, Basu et
evidence for ☐ ☐ ☒ ☐ ☐ al., 2021 and CVT; Kreimer et al 2020) is low.
However, VE outcomes are comparable to high
the critical
quality 0 vs 1 dose RCT data (Kenshe RCT,
outcomes? Safety of the intervention Barnabas et al.2021).
No
Very Mod-
included Low High
studies low erate
A growing number of lower quality observation
studies confirm the findings from intervention
studies. Studies that apply buffer periods in
the analysis (excluding participants that did not
have sufficient time between vaccination date
and outcome measurement date) and studies
which adjusted for the most confounding (i.e.,
☒ ☐ ☐ ☐ ☒ studies at the least risk of bias) were more
likely to report smaller differences in effect
between one and two doses.
5
(see the Cochrane Response Systematic
Review)
undesirable
There is uncertainty about the duration of
VALUES & PREFERENCES
6
causal link to HPV vaccination according to
GACVS), it has proven to strongly affect vaccine
uptake and acceptance of some programmes.
Values and Pro Pro Large benefits can be obtained relative to the
Unc potential undesirable effects. Reducing the
preferences of babl babl Ye Varie
No erta number of required doses to a single dose
the target y y s s
in
population: No Yes while obtaining a similarly large benefits in
terms of cancer cases averted is preferred by
Are the
vaccinees as well as by immunization
desirable programmes. It leads to reduction in individual
effects large ☐ ☐ ☐ ☒ ☐ ☐ and programme level costs while further
relative to reducing the risk of pain and AEFIs.
undesirable
effects?
Are the HPV vaccine is relatively costly compared to .
resources traditional vaccines. In addition, vaccine
required delivery cost has been demonstrated to be high
small? Un- for HPV vaccines. (Jit. M,
RESOURCE USE
No Yes Varies
certain 2021.https://doi.org/10.1016/j.jval.2020.07.01
2) A reduction from two doses to a single dose
per eligible girl will lead to considerable
programme savings.
7
From an immunization programme perspective,
the intervention will not require additional
costs and lead to cost reductions in vaccines,
human resource time and complexity
(registration, tracking).
8
Which option A small-scale informal survey among EPI .
is acceptable programmes from low and middle income
to key Inter- Com setting with current and planned HPV
Neit Un- programmes (survey carried out between July
stakeholders venti paris Both
her clear and October 2021 for WHO SAGE) indicated
(Ministries of on on
that a majority would consider adoption of a
Health,
one dose recommendation for MAC on
Immunization programmatic grounds. This survey did not ask
Managers)? specifically about a scenario to lower the
routine cohort to 1 dose. SAGE & WHO policy
☒ ☐ ☐ ☐ ☐ endorsement was mentioned as an important
criterion for NITAG decisions.
ACCEPTABILITY
Un- Varie
BILIT
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feasible to No tai Yes schedules successfully. Single dose vaccine
implement? n programmes would be easier and more
efficient.
Undesirable Undesirable
The balance between Desirable consequences
consequences consequences Desirable consequences
desirable and undesirable probably outweigh
clearly probably outweigh clearly outweigh
consequences undesirable
outweigh desirable undesirable
is closely balanced or consequences
desirable consequences consequences
uncertain in most settings
Balance of consequences in most settings in most settings
in most settings
consequences
☐ ☐ ☐ ☐ ☒
10
We recommend the We recommend
We
We suggest considering recommendation of the comparison against the
recommend
intervention intervention
the
and the comparison
intervention
Type of
recommendation ☒ ☐ Only in the context of rigorous research ☐ ☐
☐ Only with targeted monitoring and evaluation
☐ Only in specific contexts or specific (sub)populations
Recommendation Please see the WHO HPV Position Paper, published 16 December 2022
(text)
Implementation
Please see the WHO HPV Position Paper, published 16 December 2022
considerations
Monitoring and
Please see the WHO HPV Position Paper, published 16 December 2022
evaluation
Research priorities
Please see the WHO HPV Position Paper, published 16 December 2022
11
Annex 1 Grade Table 1 vs 2 doses (source: Systematic Review, Cochrane Response 2022)
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