ACIP Evidence to Recommendations Framework

Updated June 26, 2019

Question 1: Should catch-up HPV vaccination be recommended for primary prevention of HPV infection and HPV-related 

disease for all persons through age 26 years?

Population: Males aged 22 through 26 years

Intervention: Catch-up vaccination with 3 doses of HPV vaccine

Comparison: Existing HPV vaccination recommendations

Outcome: Primary prevention of HPV infection and HPV-related disease

Background:

Vaccination against human papillomavirus (HPV) is recommended to prevent HPV infections and HPV-associated diseases, including 

cancers. 

The Advisory Committee on Immunization Practices (ACIP) has recommended routine HPV vaccination since 2006 for females and 2011 

for males. Routine HPV vaccination is recommended at age 11 or 12 years; vaccination can be given starting at age 9 years. 

Catch-up vaccination has been routinely recommended since 2006 for females through age 26 years, and since 2011 for males through 

age 21 years. Catch-up vaccination also has been routinely recommended through age 26 years for men who have sex with men 

(including men who identify as gay, bisexual, or who intend to have sex with men), transgender persons, and persons with certain 

immunocompromising conditions. 

There has been interest in simplifying the immunization schedule and having the same catch-up age range for all genders. 

Three prophylactic HPV vaccines are licensed for use in the United States: 9-valent and quadrivalent HPV vaccines (9vHPV and 4vHPV, 

Gardasil 9 and Gardasil, Merck & Co., Inc., Kenilworth, NJ) and bivalent HPV vaccine (2vHPV, Cervarix, GlaxoSmithKline, Rixensart, 

Belgium). As of late 2016, only 9vHPV is being distributed in the United States. The majority of all HPV-associated cancers are caused by 

HPV 16 or 18, types targeted by all three vaccines. In addition, 4vHPV targets HPV 6 and 11, types that cause anogenital warts. 9vHPV 

protects against these and five additional types: HPV 31, 33, 45, 52, and 58. 

HPV vaccination coverage has been increasing in the United States, but is still below Healthy People 2020 target of 80% of adolescents, 

and coverage in males is lower than coverage in females. In 2017, coverage with ≥1 dose of HPV vaccine was 65% among 13–17 yearolds; 69% in females and 63% in males. 

Additional background information can be found in the relevant publication of the recommendation referenced on the ACIP website.

CRITERIA WORK GROUP JUDGMENTS EVIDENCE ADDITIONAL INFORMATION

https://www.cdc.gov/vaccines/acip/recs/grade/HPV-harmonization-etr-H.pdf
ACIP Evidence to Recommendations Framework

Updated June 26, 2019 PROBLEM

Is the problem 

of public 

health 

importance?

No Probably

no

Uncertain Probably

yes

Yes Varies

X

Approximately 33,700 cancers are 

caused by HPV annually in the United 

States, including cervical, vaginal, 

vulvar cancers in females; penile 

cancers in males; and anal and 

oropharyngeal cancers in males and 

females. Of HPV-attributable cancers 

annually, approximately 20,200 occur 

in females and 13,500 occur in males. 

First HPV infections occur soon after 

first sexual activity. HPV prevalence is 

high among both males and females.

HPV vaccination coverage has 

been increasing among

adolescents, but remains low 

among young adults. Coverage 

in males is lower than coverage 

in females. Among persons aged 

22–26 years in 2017, coverage 

with ≥1 dose of HPV vaccine

was 15% in males and 51% in 

females. 

BENEFITS & HARMS 

How 

substantial 

are the 

desirable 

anticipated 

effects?

 Minimal Small Moderate Large Don’t 

know

Varies

X

Efficacy has been demonstrated in this 

age group. 

HPV vaccines are most effective when 

given before exposure to any HPV. 

Clinical trials have shown that HPV 

vaccines are effective against infection 

and related disease due to HPV types 

that recipients are not infected with at 

the time of vaccination.

Additional benefit of vaccinating males 

in this age range would be small 

compared with the benefit of the 

existing program. The number needed 

to vaccinate (NNV) to prevent one case 

of anogenital warts, cervical 

intraepithelial neoplasia (CIN) grade 2+, 

or cancer, is 9, 22, and 202, 

respectively, under the existing 

program. In a subset of analyses in the 

HPV-ADVISE model with more 

favorable model assumptions for adult 

vaccination, these NNV would be 40;

450; and 3,260 for expanding 
ACIP Evidence to Recommendations Framework

Updated June 26, 2019

recommendations for males through 

age 26 years to harmonize catch-up 

vaccination across genders. 

CRITERIA WORK GROUP JUDGMENTS RESEARCH EVIDENCE ADDITIONAL INFORMATION

How 

substantial 

are the 

undesirable 

anticipated 

effects?

 Minimal Small Moderate Large Don’t 

know

Varies

X

HPV vaccines have an excellent safety 

profile based on large clinical trials and 

post-licensure effectiveness data. Over 

100 million doses of HPV vaccine have 

been given in the United States. 

In 9vHPV clinical trials (n=3225), there 

were no serious vaccine-related events 

among males aged 9–26 years. 

Adverse events following 4vHPV 

vaccination in 2009–2015 and 

following 9vHPV in 2014–2017 

reported to the Vaccine Adverse 

Event Reporting System (VAERS), 

have been analyzed for both males 

and females. Syncope and 

injection site reactions were 

commonly reported in both males 

and females. Headache, fatigue and 

nausea were commonly reported 

serious AEs. More than 60 million 

4vHPV doses and 29 million doses 

of 9vHPV were distributed during 

the study periods. There were no 

new or unexpected safety 

concerns.

Do the 

desirable 

effects 

outweigh the 

undesirable 

effects?

Favors 

intervention

Favors 

comparison

Favors 

both

Favors 

neither

Unclear

X

Small desirable effects outweigh minimal 

undesirable effects of HPV vaccination

What is the 

overall 

certainty of 

this evidence 

for the critical 

outcomes?

Effectiveness of the intervention

No

included

studies

4 

Very low

3 

Low

2

Moderate

1

High

X

Safety of the intervention

No

included

studies

4

Very low

3

Low

2

Moderate

1

High

X

Refer to 2011 GRADE tables for use of 

4vHPV for males and 2015 GRADE 

tables9vHPV in females and males for 

detailed assessment of the certainty of the 

evidence.

For males through age 26 years, GRADE 

evidence level is 2 (moderate) for benefits

of 4vHPV, 2 (moderate) for harms of 

4vHPV, 3 (low) for benefits of 9vHPV, and 

2 (moderate) for harms of 9vHPV.

Full grading of recommendations, 

assessment, development, and 

evaluation (GRADE) for use of 

4vHPV and 9vHPV in males have 

been available since these ACIP 

recommendations were made in 

2011 and 2015, respectively.
ACIP Evidence to Recommendations Framework

Updated June 26, 2019 VALUES

Does the 

target 

population 

feel that the 

desirable 

effects are 

large relative 

to undesirable 

effects?

No Probably

no

Uncertain Probably

yes

Yes Varies

X

In a 2013 systematic review of 22 

published studies among men aged 14–79 

years (N=8360), overall mean 

acceptability of HPV vaccine was 

moderate at 57 on a 100-point scale, and

median acceptability of HPV vaccine was 

62 (range: 8–94). 

CRITERIA WORK GROUP JUDGMENTS RESEARCH EVIDENCE ADDITIONAL INFORMATION

Is there 

important 

uncertainty 

about or 

variability in 

how much 

people value 

the main 

outcomes?

Important 

uncertainty 

or 

variability

Possibly 

important 

uncertainty 

or 

variability

Probably 

no 

important 

uncertainty 

or 

variability

No 

important 

uncertainty 

or variability

X

In the same 2013 systematic review, in the 

9 studies reporting sexual orientation, 

there was no significant difference in 

acceptability between gay/bisexual/MSM 

(n=986) and heterosexuals (n=1713).

ACCEPTABILITY

Is the 

intervention 

acceptable to 

key 

stakeholders?

No Probably

no

Uncertain Probably

yes

Yes Varies

X

In a 2018 survey of 51 immunization 

programs, 98% were in favor of 

harmonizing the recommended age for 

catch-up vaccinations to include everyone 

through age 26 years. Reasons reported by 

the majority of programs included: easier 

to implement (92%), easier to explain to 

patients (88%), and will simplify health 

department recommendations and 

guidelines (84%), easier to explain to 

providers (84%), facilitate reaching highrisk populations (84%), to create equity 

between genders (78%), and to reduce the 

burden on health care providers (76%). 

In a 2018 survey of 820 primary care 

physicians, 93% were in favor of a change 

to harmonize the recommended age for 

catch-up vaccinations to include everyone 
ACIP Evidence to Recommendations Framework

Updated June 26, 2019

through age 26 years, and 27% agreed 

that current catch-up recommendations 

with different upper ages for males and 

females have caused challenges or 

confusion. Reasons reported by the 

majority of physicians included: simplify 

the vaccination schedule (99%), easier to 

implement (97%), easier to explain to 

patients (96%), facilitate reaching highrisk populations (88%), reduce burden on 

health care providers (80%), and create 

equity between genders (61%). 

RESOURCE USE

Is the 

intervention a 

reasonable 

and efficient 

allocation of 

resources?

No Probably

no

Uncertain Probably

yes

Yes

X

In the context of the existing program, the 

incremental cost per QALY of expanding 

male vaccination through age 26 was 

$178,000 in a subset of analyses in the 

HPV-ADVISE model with more favorable 

model assumptions for adult vaccination. 

Although less cost-efficient, absolute costs 

of vaccination would likely increase by 

<5% in the long-term under the expanded 

recommendation. 

Results of health economic 

analyses are not so favorable or 

unfavorable as to make a strong 

economic case for or against 

harmonization through age 26 

years.

FEASIBILITY

Is the 

intervention 

feasible to 

implement?

No Probably

no

Uncertain Probably

yes

Yes Varies

X

As a simplifying modification to an 

existing vaccination program, this 

intervention is considered feasible to 

implement. ACIP already recommends 

catch-up vaccination for females aged 22–

26 years and some special populations. 

A simplified HPV vaccine schedule 

is expected to be easier to explain 

and remember. 

Balance of 

consequences

Undesirable 

consequences 

clearly outweigh

desirable 

consequences

in most settings

Undesirable 

consequences 

probably outweigh

desirable 

consequences

in most settings

The balance 

between 

desirable and 

undesirable 

consequences 

is closely balanced 

or uncertain

Desirable 

consequences 

probably outweigh 

undesirable 

consequences

in most settings

X

Desirable 

consequences 

clearly outweigh

undesirable 

consequences

in most settings

There is 

insufficient 

evidence to 

determine the 

balance of 

consequences
ACIP Evidence to Recommendations Framework

Updated June 26, 2019

Is there sufficient information to move forward with a recommendation?

Yes No 

Policy option for 

ACIP 

consideration ACIP does not recommend the 

intervention

ACIP recommends the intervention for 

individuals based on shared clinical 

decision-making

ACIP recommends the intervention

X

Recommendation 

(text)

Routine and catch-up age groups

ACIP recommends routine HPV vaccination at age 11 or 12 years; vaccination can be given starting at age 9 years.*

ACIP also recommends catch-up vaccination for persons through age 26 years who are not adequately vaccinated.†

Special populations and medical conditions

The above recommendations for routine and catch-up age groups also apply to MSM;‡ transgender people; and 

people with immunocompromising conditions.

Additional 

considerations

(optional)

CDC continues to monitor HPV vaccine safety and impact of the vaccination program on HPV-attributable outcomes, 

including prevalence of HPV infections, anogenital warts, precancers, and cancers. ACIP reviews results from 

ongoing studies, vaccine trials, and health economic analyses as data become available, and updates vaccine policy 

as appropriate.

 *Recommended 2-dose and 3-dose schedules and intervals are unchanged from prior recommendation (Meites et al, MMWR 2016).

†

Definitions of persons considered adequately vaccinated are unchanged from prior publication (Meites et al, MMWR 2016).

‡Men who have sex with men; includes men who identify as gay or bisexual, or who intend to have sex with men
ACIP Evidence to Recommendations Framework

Updated June 26, 2019

Final deliberation and decision by the ACIP

Final ACIP 

recommendation

ACIP does not recommend the 

intervention

ACIP recommends the intervention 

for individuals based on shared 

clinical decision-making

ACIP recommends the intervention

X

ACIP 

considerations

Fourteen ACIP members voted unanimously to recommend harmonization across genders of the upper age for 

catch-up vaccination through age 26 years.

ACIP placed high value on prevention of HPV infections and related disease; simplification of the immunization 

schedule to improve acceptability and feasibility for programs and vaccine providers; and gender equality, according 

to the Healthy People 2020 goal to achieve health equity, eliminate disparities, and improve the health of all groups.

This Evidence to Recommendation table is based on the GRADE Evidence to Decision framework developed through the DECIDE project. Further 

information is available athttp://www.decide-collaboration.eu/evidence-decision-etd-framework. Framework last updated 19 June 2019.