Health and economic impact of Quadrivalent HPV vaccine over

Bivalent HPV vaccine in minimizing the HPV prevalence

Abstract:

Human papillomavirus is an infectious virus most commonly spread during

vaginal or anal sex (sexually transmitted), also spreads through close skin-to-skin
touching during sex. It belongs to the family Papillomaviridae which has non enveloped
DNA virus. As HPV has no symptoms as Most types do not cause any problems, the
only way people find out about it is by the presence of genital warts . There is no cure
for HPV but it's preventable. HPV vaccines prevent certain types of human
papillomavirus but not all. The two types of vaccines which are compared here are
quadrivalent and bivalent HPV vaccines.

Several models, mainly the Markow model and the transmission dynamic model,
have been published to predict the cost effectiveness of various vaccination strategies.
In all models, assumptions are made on the basis of studies of the efficacy of the
vaccines, measured by surrogate end points, and by immunological follow-up studies.
And in every model evaluation, the bivalent vaccine would be cost effective only if it
were a dozen or so pounds cheaper than the quadrivalent vaccine [6].

HPV-related disease remains a significant source of morbidity and mortality in

developing and developed nations, underscoring the need for HPV- vaccination
programs with high population coverage [4]. The bivalent vaccine (BV), which protects
against genotypes 16/18, and the quadrivalent vaccine (QV), which protects against
genotypes 6/11/16/18, are both available as preventative HPV vaccinations. Given their
success in treating genital warts and cervical lesions, HPV vaccinations have the
potential to shield against cervical and anogenital malignancies linked to the virus.

Introduction:

Globally, cervical cancer is the second most common cancer. HPV is a necessary
cause of cervical cancer and contributes to the development of a number of other
cancers including anogenital carcinomas, head/neck cancers and genital warts.
Vaccines play a key role in disease prevention and in the stability and maintenance of
public health [5]. CDC and FDA continue to monitor the safety of the vaccine via three
mechanisms: the Vaccine Adverse Event Reporting System (VAERS), the Vaccine
Safety Datalink (VSD) Project and the Clinical Immunization Safety Assessment (CISA)
network.A recent vaccine approved for HPV, the Food and Drug Administration (FDA)
is the recombinant quadrivalent human papillomavirus (HPV) vaccine. February 2019,
92 countries or territories had introduced HPV vacci- nation programmes distributing
over 270 million vaccine doses during the last decade [1]. Numerous clinical trials have
shown that the HPV quadrivalent vaccine is beneficial in the management of HPV by
avoiding vaccine subtype-related persistent infection and precancerous lesions. Based
on an evaluation of recorded adverse events submitted through governmental
databases and examined by independent researchers, it is also recognized as a
generally safe and well-tolerated vaccination.

Over 40 human papillomavirus (HPV) genotypes are known to infect the

anogenital tract. Persistent infection with specific high-risk (HR) strains of human
papillomavirus is the root cause of almost 99% of cervical cancer cases (HPV). The
bivalent vaccine, which protects against HPV-16 and HPV-18, which are responsible for
over 70% of cervical malignancies, was first made available in the UK in 2008. In order
to protect against HPV-6/11, which is responsible for 90% of genital warts, the program
upgraded to the quadrivalent vaccine in 2012. Two HPV vaccines, targeting
HPV-6/11/16/18 (quadrivalent) and HPV-16/18 (bivalent), have demonstrated 93–100%
efficacy against cervical lesions and vaccine-type persistent infection. In comparison to
the quadrivalent vaccine, a new meta-analysis reveals that the bivalent vaccine gives
higher cross-protection against HPV- 31/33/45. However, this protection may fade over
time. A head-to-head immunogenicity experiment comparing the bivalent and
quadrivalent vaccines revealed a considerably stronger antibody response against
HPV-16/18 for the bivalent vaccine, which could indicate longer duration of protection.
Many nations have authorized the use of two preventive HPV vaccinations, a bivalent
and a quadrivalent vaccine, in adolescent girls and young women to prevent cervical
cancer. Clinical studies have demonstrated very high vaccine efficacy against the two
high-risk types present in both vaccines as well as some evidence of cross-protection
against HPV-31 for both vaccines and HPV-33 and HPV-45 for the bivalent vaccine.
During these trials, fever, nausea, dizziness, injection-site pain, swelling, erythema,
pruritus and bruising were noted as the most commonly reported adverse events [11].

Clinical trials have demonstrated that both vaccines are highly effective in the
prevention of persistent infection and cervical lesions associated with HPV vaccine
types, with approximately 100% efficacy in the prevention of HPV16- and
HPV18-related cervical intraepithelial neoplasia grade 3 in young women [3]. The aim of
this study is to determine the health impact and cost-effectiveness of introducing a
human papillomavirus (HPV) vaccination programme with a quadrivalent vaccine
alongside existing bivalent vaccine. The HPV vaccines appear safe and effective.
Additional clinical research on the vaccines on women outside the currently approved
age ranges and in males is necessary. Studies on longer-term outcomes, including
cervical cancer and the emergence of new viral genotypes are also necessary[5].
Cost-effectiveness is a key criterion for policy decisions. vaccine does not alter the
course of infection or pre-existing disease. Routine administration of vaccines in many
situations is a cost-effective strategy to minimize preventable diseases and decrease
disease complications.

The aim was to estimate the effectiveness of bivalent and quadrivalent vaccines
separately. To our knowledge, this is one of the first studies assessing the effectiveness
of BV and QV vaccines in the same population setting[2]. The HPV vaccine's potential
for improving public health has not yet been fully realized. Preadolescents are routinely
advised to get vaccinated since it is most effective when given before HPV exposure
(usually ages 11-12 years). Unfortunately, the full benefits of HPV vaccination are still
far from being understood. HPV-related infections continue to pose significant public
health issues for both developing and industrialized countries, despite the discovery of
effective preventative vaccinations. With the biggest ongoing burden of HPV-related
diseases, low-income countries appear to have the lowest rates of HPV vaccination.
 Their cost threshold analysis revealed that both vaccines would be equally
cost-effective if the bivalent Cervarix vaccine, which protects against HPV types 16 and
18, cost £13 (€15; $21–£21) less per dose than the quadrivalent Gardasil vaccine.
However, the bivalent vaccine would be less effective because it does not prevent
anogenital warts.Only side effects that were recognized and listed were recorded, and
other negative outcomes could not be attributed to the immunizations. The bivalent
vaccine confers greater cross-protection against HPV- 31/33/45 than the quadrivalent.
In one observer blinded head to head study the bivalent vaccine induced a higher, more
sustained immune response than the quadrivalent vaccine[9]. It has been estimated that
the Italian programme, which uses the bivalent vaccine, would prevent 295 more deaths
from cancer but 25 848 fewer cases of genital warts than if it used the quadrivalent
vaccine[10]. The administration of the quadrivalent HPV vaccine is recommended at the
preadolescent visit of young girls and as a catch up vaccine for girls ⁄ young women
ages 13–26 years not previously vaccinated against HPV [12].

Conclusion:

Finally, we should not forget that the vaccination programme aims to save lives
from cervical cancer [8]. The HPV quadrivalent vaccine has been effective in the
management of HPV by preventing vaccine subtype-related persistent infection and
precancerous lesions as evidenced by numerous clinical trials. It is also regarded as a
generally safe and well-tolerated vaccine, based on an assessment of reported adverse
events submitted through governmental databases and analyzed by independent
researchers. The HPV vaccines appear safe and effective. Additional clinical research
on the vaccines on women outside the currently approved age ranges and in males is
necessary. Studies on longer-term outcomes, including cervical cancer and the
emergence of new viral genotypes are also necessary.[5]

The literature review tells us that when it comes to cost effectiveness its the
quadrivalent vaccine, and when it comes to efficacy we preferred bivalent vaccine over
the quadrivalent vaccine, when it comes to the number of diseases covered we again
preferred quadrivalent vaccine (as the name suggests protective against 4 types of hpv
that is hpv type 6, 11, 16, and 18). Considering all the pros and cons of both
quadrivalent and bivalent vaccines, it’s concluded that quadrivalent vaccines have more
advantages over bivalent HPV vaccines.

As there’s no cure for HPV so either of the vaccines should be given to the
population, keeping in mind that “Prevention is better than cure“ , and in case of HPV
there’s no cure , so we should take precautions and prevent it .

References:

1. J.M.L. Brotherton, P.N. Bloem, Population-based HPV vaccination programmes

are safe and effective: 2017 update and the impetus for achieving better global
cov- erage, Best Pract. Res. Clin. Obstet. Gynaecol. (2017).
2. Effectiveness of bivalent and quadrivalent human papillomavirus vaccination in
Luxembourg Ardashel Latsuzbaiaa,⁎, Marc Arbynb, Jessica Tappa, Marc
Fischerc, Steven Weyersd, Pascale Pesche, Joël Mossonga.
3. Comparative cost-effectiveness of the quadrivalent and bivalent human
papillomavirus vaccines: A transmission-dynamic modeling study Marc Brisson
a,b,c,∗ , Jean-François Laprise a , Mélanie Drolet a,b , Nicolas Van de Velde a,b ,
Eduardo L. Francod, Erich V. Kliewere,f,g, Gina Ogilvieh, Shelley L. Deeksi,
Marie-Claude Boilyc.
4. Impact and Effectiveness Of the Quadrivalent Human Papillomavirus Vaccine: A
Systematic Review of Ten Years of Real-World Experience Suzanne M.
Garland1, Susanne K. Kjaer2, Nubia Muñoz3, Stan L. Block4, Darron R. Brown5,
Mark J. DiNubile6, Brianna R. Lindsay6, Barbara J. Kuter6, Gonzalo Perez6,7,
Geraldine Dominiak-Felden8, Alfred J. Saah6, Rosybel Drury8, Rituparna Das6,
and Christine Velicer6.
5. Quadrivalent human papillomavirus (HPV) vaccine: a review of safety, efficacy,
and pharmacoeconomics, T. C. Pomfret PharmD BCPS, J. M. Gagnon Jr
PharmD BCPS and A. T. Gilchrist PharmD BCPS.
6. Comparing bivalent and quadrivalent human papillomavirus vaccines: economic
evaluation based on transmission model, Mark Jit,1 Ruth Chapman,1 Owain
Hughes,2 Yoon Hong Choi1.
7. Efficacy of Quadrivalent HPV Vaccine against HPV Infection and Disease in
Males, Anna R. Giuliano, Ph.D., Joel M. Palefsky, M.D., Stephen Goldstone,
M.D., Edson D. Moreira, Jr., M.D., Mary E. Penny, M.D., Carlos Aranda, M.D.,
Eftyhia Vardas, M.D., Harald Moi, M.D., Heiko Jessen, M.D., Richard Hillman,
M.D., Yen-Hwa Chang, M.D., Daron Ferris, M.D., Danielle Rouleau, M.D., Janine
Bryan, Ph.D., J. Brooke Marshall, Ph.D., Scott Vuocolo, Ph.D., Eliav Barr, M.D.,
David Radley, M.S., Richard M. Haupt, M.D., and Dalya Guris, M.D.
8. Comparing bivalent and quadrivalent HPV vaccines Modelling can help, but the
tender price determines cost.
9. Einstein MH, Baron M, Levin MJ, Chatterjee A, Edwards RP, Zepp F, et al;
HPV-010 Study Group. Comparison of the immunogenicity and safety of Cervarix
and Gardasil human papillomavirus (HPV) cervical cancer vaccines in healthy
women aged 18-45 years. Hum Vaccin 2009;10:705-19.
10. Capri S, Gasparini R, Panatto D, Demarteau N. Cost-consequences evaluation
between bivalent and quadrivalent HPV vaccines in Italy: the potential impact of
different cross-protection profiles. Gynecol Oncol 2011;121:514-21.
11. Merck & Co., Inc (2009) GardasilÒ [package insert on the Internet]. Whitehouse
Station, NJ: Merck & Co., Inc.
12. Centers for Disease Control and Prevention (2007) Quadrivalent Human
Papillomavirus Vaccine; Rec- ommendations of the Advisory Committee on
Immunization Practices (ACIP). MMWR, 56(RR02), 1–24.