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Review Article

Human papillomavirus vaccination: Review and

roll out plan in Delhi
Sandeep Sachdeva, Ruchi Sachdeva1
Department of Community Medicine, North Delhi Municipal Corporation Medical College and Hindu Rao Hospital, NewDelhi,
Department of Respiratory Medicine, Employees State Insurance Corporation Medical College, Faridabad, Haryana, India

This manuscript reviews and describe the burden of cervical cancer in world and India, epidemiology of HPV infection, screening
methods, prevention, control strategy, types of HPV vaccines, schedule, age of administration, dose, route, anatomical site of human
papillomavirus vaccination, cold chain, vaccine coverage and roll out plan in Delhi, India.
Keywords: Adolescent, cervical cancer, epidemiology, immunization, malignancy, prevention, program, women


Globally, there were 14.1 million new cancer cases
diagnosed during 2012 while 8.2 million died of cancer,
and according to the estimate, 19.3 million new cancer
cases would be diagnosed by the year 2025. The burden of
cancer cases and deaths is high in less developed regions
of the world, accounting for 57% of the total new cancer
cases and 65% of global cancer deaths(GLOBOCAN
2012). Cervical cancer is the fourth most common
cancer in women with an estimated 528,000 new
cases in the world, with estimated 266,000 deaths
accounting for 7.5% of all female cancer deaths in the
year 2012. India accounted for 23.2%(123,000) of new
global cervical cancer cases and 25.1%(67,000) of
cervical cancerrelated deaths.[1] The agestandardized
incidence of invasive cervical cancer in India is 27 and
mortality of 15.2/100,000 women.[2] Figure1 depicts
agestandardized cervical cancer incidence rate across
Corresponding Author: Dr.Sandeep Sachdeva,
Department of Community Medicine, Hindu Rao Hospital
and North Delhi Municipal Corporation Medical College,
NewDelhi110007, India.
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the globe(World Health Organization[WHO]). Over

the past three decades, cervical cancer rates have
fallen in most of the developed world largely as a
result of organized screening and treatment programs
reaching larger segment of population albeit at a cost.
In contrast, rates in most developing countries have
risen or remained unchanged. Ninety percent of cervical
cancers is squamous cell cancers and the other 10% is


Human papillomavirus(HPV) is one of the most
common viral infections of the reproductive tracts of
both females and males. Based on a metaanalysis, the
adjusted HPV prevalence worldwide among women
with normal cytological findings was estimated to be
11.7%(95% confidence interval: 11.611.7%).[6] Up
to 80% of women acquire an HPV infection in their
lifetime.[7] The prevalence figures in men are limited;
a systematic review of genital HPV among men in
subSaharan Africa found prevalence of any HPV type
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Cite this article as: Sachdeva S, Sachdeva R. Human papillomavirus
vaccination: Review and roll out plan in Delhi. CHRISMED J Health Res

2016 CHRISMED Journal of Health and Research | Published by Wolters Kluwer -Medknow

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Sachdeva and Sachdeva: Cervical cancer and HPV vaccination

Figure1: World map showing the incidence of cervical cancer, 2012(agestandardized rate per 100,000 women)

between 19.1% and 100%.[8] Approximately 200 HPV

genotypes(types) have been described.[9] However,
persistent infection by oncogenic HPV types 16 and 18
is responsible for the development of cervical cancer.
Together, these two types account for around 70% of
cervical cell carcinomas.[10] HPV infections cause several
different cancers including vaginal, vulvar, penile,
oropharyngeal, and anal cancers.[11]
In addition, HPV types 6 and 11 cause anogenital warts
and recurrent respiratory papillomatosis. Cervical
cancer occurs only in a small fraction of those infected
as majority of subclinical HPV infection resolves
on itself while in smaller proportion it persists and
takes further 1020years to develop into cancer. It
is estimated that no more than 2% of all women in
lowresource countries will develop cervical cancer
during their lifetime. The risk of developing squamous
cell carcinoma of the cervix is about 400times higher
following infection with HPV16 and about 250times
higher following infection with HPV18 compared to
the risk in uninfected women.[12]


Compared with diseases attributable to noninfectious
causes, it is often easier to prevent or treat diseases
caused by infectious agents. The identification of HPV
as the infectious agent responsible for cervical cancer
in the early 1980s by zur Hausen was hailed as a
major advances.[13] This fundamental discovery was
followed up by additional research resulting in the
development of vaccines and other screening methods.
Comprehensive prevention and control strategies
include prevention with HPV vaccination for young

girls, screening and treatment for women diagnosed

with precancerous lesions, and treatment and palliative
care for women with invasive cervical cancer. Screening
for precancerous lesions can be done in several ways
including cervical cytology(Papanicolaoutest), visual
inspection of the cervix with acetic acid(VIA), or testing
for HPV DNA. Each of these strategies has specific
advantages, weakness, and health system requirements
while mainstay in lowresource setting is VIA strategy.
Table1 depicts sensitivity and specificity of various
screening methods.[14]
Vaccination with HPV types may not result in protection
of all recipients, and the women subjects receiving
complete immunization schedule would still be advised
to undergo ageappropriate screening for premalignant
lesions. The longterm benefit of vaccination would
be accrued only when at least 75% of the targeted
preadolescent population is covered by prophylactic
vaccination. Research has proved that vaccinating
preadolescent girls, viz., boys, is more costeffective
strategy in preventing cervical cancer in later life.
Health education, personal hygiene, male circumcision,
and tobacco control would further lead to reduction of
cervical cancer burden.[15] Details are shown inTable2.


The WHO recommends that HPV vaccination to be
introduced in the national immunization program
considering disease burden and costeffectiveness
strategy. More than 63(32.6%) countries in the
world have introduced HPV vaccine in their national
immunization schedule by the end of 2014.[16] Efforts are

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Sachdeva and Sachdeva: Cervical cancer and HPV vaccination

being made to roll out HPV vaccine in other countries

with financial assistance from global alliance for vaccine
and immunization(GAVI). Figure2 depicts world map
showing countries with introduction of HPV vaccine
in their national health program for girls, especially
developed countries and other GAVI supported vaccine
roll out countries(Source: Program for Appropriate
Technology in Health[PATH], 2015). Australia, the
first country in the world to introduce HPV vaccine in
National Immunization Program for girls during 2007,
has consistently recorded coverage of three doses of
HPV vaccine among 70% of females aged 15years and

above since 2009.[17] In the United States, for the year

2014, girls aged 1317years who received at least one
dose of HPV vaccine was 60.0%(3.3% points higher
than 2013 figure) while only 39.7% completed the three
dose schedule.[18]


The two prophylactic firstgeneration HPV vaccines,
quadrivalent HPV type6/11/16/18 vaccine and
bivalent HPV type16/18 vaccine, were licensed
in 2006 and 2007, respectively, under the names

Table1: Screening methods for cervical cancer


Conventional cytology

HPV DNA test


Specificity (%)
Number of visits required
for screening and treatment

2 or more

2 or more

1 or 2

Assessed over the last 50years in a

wide range of settings in developed and
developing countries. Test must be repeated
every few years due to low sensitivity

Assessed over the last decade in

many developed country settings; just
beginning in developing countries.
Due to high sensitivity screening may
be done with less frequency

Assessed over the last

decade in many settings
in developing countries
with good results

VIA: Visual inspection with acetic acid, HPV: Human papillomavirus

Table2: Prevention and control of cervical cancer over the life course
Primary prevention

Secondary prevention

Tertiary prevention

Women >30years of age

Women >30years of age
HPV vaccination
Health education and counseling(delay of sexual activity,
Screening(e.g., VIA) and treatment of
Treatment of invasive cancer at any
avoidance of high risk sexual behavior, personal hygiene,
precancerous lesions
age(ablative surgery, radiotherapy,
natural history of disease, risk, signs/symptoms, improving Treatment of reproductive tract infections chemotherapy, palliative care)
health seeking behavior immunization, screening, etc.)
Tobacco control
Condom promotion
Male circumcision
Community mobilization
Training of health staff
HPV: Human papillomavirus, VIA: Visual inspection with acetic acid

Figure2: World map showing countries with human papillomavirus vaccine introduced in the National Health Program


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Sachdeva and Sachdeva: Cervical cancer and HPV vaccination

of Gardasil Silgard (Merck and Co., Inc, NJ,

USA) and Cervarix (GlaxoSmithKline, Brentford,
London) and the secondgeneration 9valent HPV
type6/11/16/18/31/33/45/52/58 vaccine with broader
cancer coverage has also received the US Food and
Drug Administration approval in December 2014
under the name of Gardasil 9(Merck and Co, Inc.).
Quadrivalent and 9valent HPV vaccines are licensed
for use in females and males while bivalent HPV vaccine
is licensed for use in females only. Gardasil prevent
cervical, vulvar, vaginal, anal cancer, precancerous or
dysplastic lesions, and genital warts. By preventing HPV
infection and disease due to HPV31/33/45/52/58, the
9vHPV vaccine has the potential to increase prevention
of cervical cancer from 70% to 90%. In addition, the
9vHPV vaccine has the potential to prevent 8595% of
HPVrelated vulvar, vaginal, and anal cancers. These
vaccines are prophylactic in nature, i.e.,they do not
treat the underlying cervical lesion.[1923] Both vaccines
are intended to be administered before the onset
of sexual activity, i.e.,before first exposure to HPV
infection. There are no adverse effects observed among
females and offspring, yet data are limited therefore not
recommended for pregnant mothers. Using recombinant
technology, both generations of vaccines are prepared
from purified L1 structural proteins that selfassemble
to form HPV typespecific empty shells or viruslike
particles. Neither of these vaccines contains live
biological products or viral DNA, and both are therefore
noninfectious; they do not contain any antibiotics or
preservative agents.


Appropriate age, dose, schedule, route, site of
administration, and cold chain preservation of vaccine
are shown in Table3.[24] A recent published research
lends support to twodose regimen at least 6month
apart for routine vaccination of young girls, and the
shortterm protection afforded by one dose of HPV
vaccine against persistent infection with HPV 16, 18,
6, and 11 is similar to that afforded by two or three
doses of vaccines but merits further assessment.[25]
Mathematical models have shown in highincome
countries that a twodose vaccination conferred more
than 1020years protection. Furthermore, clinical
trials are ongoing to evaluate alternative/reduce dosing
schedules for 9vHPV.[25] Each manufactured vaccine is
produced in a unique manner, and hence, once started
with a particular brand of vaccine, ideally should be
completed with the same type of vaccine. However,

in case of nonavailability or nonawareness of type

of first vaccine, switch over to any type is advised to
complete the immunization series. Followup trials have
shown that protection against HPV lasts for at least
5year postvaccination for the quadrivalent vaccine
and 6.4years for the bivalent vaccine.[26,27] However,
booster dose is not recommended as these vaccines
behave similar to hepatitis B virus vaccine where titers
per se may not be measurable, yet immune memory
exists and shows anamnestic effect.[28] The HPV vaccine
needs to be shaken well before administration and can
be safely coadministered along with other vaccine
such as hepatitis B at different sites in human body
using separate injection/syringe. All HPV vaccines are
freezesensitive and should be preserved at 28C only.
Contraindications to vaccine include hypersensitivity/
allergic reactions to yeast or with previous dose of
vaccine especially Gardasil 9 and Gardasil. Up to 80%
recipient may develop local adverse effects such as
injection site pain, swelling, and erythema. The other
less common side effects include fever, nausea, and
dizziness. Each subject after receiving vaccine should be
observed for at least 15min since they may rarely also
develop syncope/fainting episode or anaphylaxis(rate,
1.72.6/106 doses).[29]


The Indian Academy of Pediatrics recommended
inclusion of HPV in its immunization schedule way back
in 2007, and more robust reaffirmation for inclusion
was made recently also.[30] HPV vaccines were licensed
in India by the Drug Controller General of India in
20082009. Lot of academic, medical, public health,
advocacy groups, nongovernmental organizations
and parliamentary discussion, debate arguments, and
scientific publications have happened for and against[31]
starting of population based mass HPV vaccination in the
country. HPV vaccine delivery and demonstration project
in AndhraPradesh and Gujarat led by an international
nonprofit organization, PATH, was proposed for the
interim period 20092011 but suspended in 2010 due to
public concern, controversy, social and political pressure
arising from death of girls who received HPV vaccine.[32,33]
Subsequent investigations proved that these deaths were
not linked to vaccination. However, the project further
could not see the light of the day but collaterally led to
the development of more stringent regulatory, ethical,
quality control and monitoring environment of health
and human research in country. This event further
reinforced the importance of health communication,

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Sachdeva and Sachdeva: Cervical cancer and HPV vaccination

Table3: Human papilloma virus vaccination schedule


Age of

Girls and women:
(quadrivalent 9 through 26years;
males: 9 through
Girls and women:
9 through 26years
Gardasil 9


Schedule* Route

0.5 ml
0, 2 and
of liquid
6 months
0.5 ml
0, 1 and
of liquid
6 months

Girls and women:

0.5 ml
0, 2 and
9 through 26years; of liquid
6 months
males: 9 through


Intramuscular Deltoid region of

upper arm or high
anterolateral aspect
of thigh

Cold chain


Single dose vial (0.5 ml)
life: 36 months) in a package of 1, 10
and 100 vials
life: 36 and
48 months)

Intramuscular Deltoid region of

upper arm or high
anterolateral aspect
of thigh

Single and two dose

(0.5 ml and 1.0 ml vial);
package of 1, 10 and
100 vials
Single dose vial (0.5 ml);
1 and 10 vials

*Girls <15years(9-13years) require two doses at least 6 months apart but within 12-15 months of first dose; girls >15years or immunecompromised(e.g., HIV) women
require three doses for full protection. HPV: Human papillomavirus

consequence of negating and poor management of rumor

and misinformation in community, confidence, trust
buildup, and involvement of multiple stakeholders in
decisionmaking process.
The licensed vaccine was available in project sites
for free and private sector in the country at a very
high cost albeit scantily. Since there is no vaccine
coverage data available other than project sites, in all
probability, vaccine coverage is negligible at national
level considering awareness, access, availability, cost,
risk, and safety concern issues. Vaccine delivery strategy
at project site(AndhraPradeshKhammam District and
GujaratVadodara District) included school and health
centerbased delivery with delivery either at three fixed
time points(i.e.,campaign approach) or routine delivery
approach. Nearly 27,169 girls through the age group
of 1014years were eligible to receive vaccine within
and outside school purview at both sites. The study on
complete vaccine(three doses of HPV) coverage revealed
that campaign approach achieved 77.287.8% coverage
whereas monthly delivery achieved 68.483.3% in the
project sites.[34]
Several private sector organizations such as the
Indian Immunologicals Ltd., Hyderabad; Shantha
Biotechnics Ltd., (wholly owned subsidiary of
Sanofi), Hyderabad; Bharat Biotech Interl Ltd.,
Hyderabad; Serum Institute of India Ltd., Pune;
Gennova Biopharmaceuticals Ltd., Pune; and Virchow
Biotech Pvt. Ltd., Hyderabad, and also public sector
organizations such as Translational Health Science
and Technology Institute, Gurgaon, Haryana; and
Institute of Cytology and Preventive Oncology, Noida,
Uttar Pradesh, are actively involved in HPV vaccine
development in India.[35]



Delhi, the National Capital of Country, has a certain
unique set of characteristics due to historical
background, high connectivity, largescale migration,
varied socioculturalreligiouseconomicpolitical
environment, combination of urban, urbanizedrural
and slum population residing in nine administrative
zones. For the purpose of milestones to name a few,
Delhi was the first state in the country to initiate pulse
polio campaign(1995) and hepatitis B immunization
for infants(partly in 1998 and fully in 2004) in project
mode, etc. In the current context, the Government
of Delhi in 2016 has announced that HPV vaccine
to be included in immunization schedule of state for
administration of adolescent girls, again a first in the
country.[36] This will be introduced in a phased manner,
targeting firstly the girls studying in class sixth of
government schools in age group of 913years with
two doses. The vaccine will be imported from outside
the country since currently it is not produced in India
but at a subsided cost of Rs. 450/against the market
price of Rs. 3000/per dose.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.


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