Quantifying the Extent of Human Papillomavirus quadrivalent

recombinant vaccine (HPV4) Wastage in a Safety Net Population

Felicia Ratnaraj
1
; Diane M. Harper
1,2
Inge Verdenius
3
, Anne Arey
1,2
, Beth Rosemergey
1,2
, Gerard J Malnar
1,2
, Jeffrey Wall
1

1
University of Missouri-Kansas City School of Medicine,
2
Truman Medical Center,
3
Radboud University, Nijmegen, the Netherlands
Introduction:

Results for Insufcient Numbers of Doses :
Discussion:

Human Papillomavirus quadrivalent recombinant vaccine
(HPV4), a vaccine requiring three timed doses, provides
efcacy against oncogenic Human Papillomaviruses (HPV
types 16 and 18).
1

Currently, at $98.60 per dose via the CDC and at $135.45
per dose via private sector, HPV4 is the most expensive
prophylactic vaccine marketed on an individual and national
basis.
2

The completion rates of the on-time three-dose HPV4 series
range from 12-37% within the US.
3

Other three dose vaccines have a 40-45% on-time
completion rate for adolescents and young adults, with only
1-2% receiving mistimed doses.
4
However, the cost of those
vaccines are 1/10 the cost of HPV4.
1

The primary purpose of this study is to quantify the wastage
of HPV4 in a safety net health care system and to determine
the predictors of wastage by HPV4 dose, to guide future
cost-effective prevention programs.
Methods:

A retrospective study of HPV4 usage was conducted
between July 1, 2006 and October 1, 2009, the time frame
when HPV4 was the exclusive HPV vaccine approved by
the FDA.
The date, dose number, visit type and subject
characteristics were abstracted from the electronic medical
records for all females 10-26 years old who received HPV4
in the TMC system.
Unique dose wastage was classied as a dose given too
early or too late from the prior dose, dened for dose 1-2 as
< 4 weeks, for dose 2-3 as < 12 weeks and for dose 1-3 as
< 24 weeks; or for dose 1-2 > 26 weeks or 1-3 > 52 weeks.
Dose wastage was also dened as less than three doses in
a series (singleton or doublets) or the fourth dose when a
fourth dose was given.
This research was approved by the TMC Privacy Board and
the UMKC Adult Health Sciences Institutional Review
Board.
Three quarters of the wasted doses were either singletons
(651/1961) (missed second and third dose) or doublets
(818/1961) (missed third dose) (Figure 1).
Over half of the singleton and doublet doses were
administered at a visit without a physician at which only
HPV4 was provided, termed a HPV4-only visit (Figure 2).
Singleton doses were administered signicantly more
frequently at postpartum visits and in the year 2009
compared to a dose in a doublet. A doublet dose occurred
signicantly more often than a singleton dose if it was given
at a HPV4-only visit, a preventive visit, a follow up from an
acute illness visit or in 2010 (Figure 2 and 3).
Studies of HPV4 and other vaccines to date have shown
that compliance with dosing intervals is critical for the
induction of immune response and long term memory.
Insufcient numbers of and mistimed HPV4 doses have had
little rigorous attention but substantially and negatively
impact the cost effectiveness of the vaccination program.
Our study showed that HPV4 doses as administered in our
safety net system cannot provide the expected efcacy to
reduce abnormal Pap screening, colposcopies, and
treatment procedures.
5
The vast majority of the wasted doses in our study were due
to insufcient numbers of doses.
Thus HPV2, which is effective in less than three doses,
might be more cost effective.
6
Among uniquely mistimed doses, signicantly fewer doses
were early (92/225) than late (133/225) (41% vs. 59%).
Among early doses, third doses were early from the rst
dose signicantly more often than second doses from the
rst (26% vs. 2%); likewise, among the late doses, third
doses were late from the rst dose signicantly more often
than second doses from the rst (38% vs. 21%) (Figure 4).
Mistimed second doses occurred signicantly less often than
mistimed third doses when provided at a HPV4-only visit
(37% vs. 53%) and more often when provided at a
postpartum visit (22% vs. 8%) (Figure 5).
After adjusting for all visit types and year of administration ,
only the postpartum visit administration increased the
likelihood of a mistimed second dose compared to a
mistimed third dose (aOR=5.56 (95% CI: 2.21, 14.04).
Likewise, the likelihood of a mistimed second dose was
signicantly higher than a mistimed third dose in years 2008,
2009 and 2010 of the HPV4 implementation program.

Conclusion:

Until behavioral changes can be implemented to ensure
three doses are administered on time, using HPV2, as it is
effective in less than three doses, or encouraging
adherence to screening guidelines will offer more cost
effective cervical cancer prevention.
Reference:

1.Puman aplllomavlrus vacclne.
hup://www.cdc.gov/vacclnesafeLy/vacclnes/Pv/lndex.hLml. Accessed lebruary
9, 2013.
2.CuC vacclne rlce LlsL. hup://www.cdc.gov/vacclnes/programs/vfc/awardees/
vacclne-managemenL/prlce-llsL/. Accessed lebruary 10, 2013.
3.CenLers for ulsease ConLrol and revenuon. nauonal and SLaLe vacclnauon
Coverage Among AdolescenLs Aged 13 1hrough 17 ?ears - unlLed SLaLes, 2011.
MMW8. 2012,61:671-677.
4.nelson !C, 8luner 8C, 8ounds L, eL al. Compllance wlLh muluple-dose vacclne
schedules among older chlldren, adolescenLs, and adulLs: resulLs froma vaccln
e safeLy daLallnk sLudy. Am! ubllc PealLh. 2009,99(suppl 2):S389-97.
3.Parper uM, vlerLhaler SL, SanLee !A. 8evlew of Cardasll. !ournal of vacclnes and
vacclnauon. 1:107. dol:10.4172/2137-7360.10001.
6.krelmer A8, 8odrlguez AC, PlldeshelmA, eL al. roof-of-prlnclple evaluauon of Lhe
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Results for Mistimed Doses:
Figure 4: Mistimed doses among
Triplet and Quadruplets doses
2993 doses of HPV4 were administered between July 1,
2006 and October 1, 2009 in the TMC health care system.
66% (1961/2993) of patients received insufcient number of
or mistimed HPV4 doses to induce the expected immune
response necessary for HPV infection prevention. #

Results:

Results for Insufcient Numbers of Doses vs.
Mistimed HPV4 Doses :
Insufcient number of doses occurred signicantly more
commonly than mistimed doses when the dose was given to
an older female and at a postpartum exam (Table 1).
Mistimed doses occurred signicantly more commonly than
insufcient numbers of doses when the dose was provided
earlier in the program administration and if given at a follow
up visit (Table 1). # Adjusted OR (95% CI)
Year of Administration 0.997 (0.996, 0.997)
Age 1.07 (1.02, 1.13)
Visit Type #
HPV4-only referent
Acute Illness 1.23 (0.66, 2.32)
Follow up after an acute illness 0.36 (0.15, 0.83)
Preventive Visit 0.80 (0.49, 1.32)
Postpartum Visit 6.27 (3.55, 11.07)
Other 1.07 (0.57, 2.01) 8ed - lndlcaLes slgnlcance
Table 1: Predictors of
Insufcient HPV4 Dose
numbers vs. Mistimed
HPV4 Doses