Indian J Med Res 127, June 2008, pp 511-513
Editorial
HPV vaccine: End to women’s major health problem?
The Advisory Committee on Immunization
Practices (AICP) of Centers for Disease Control and
Prevention has recommended, the universal
administration of three doses of the quadrivalent HPV
(human papilloma virus) vaccine against cancer
(Gardasil) in girls 11 or 12 yr of age 1 . This
recommendation allows physicians to immunize girls
as young as nine years and to vaccinate women up to
26 yr of age at their discretion. With HPV infection and
cervical cancer incidence so common in India, the
availability and use of this vaccine is a matter of urgent
need at present.
HPVs are small nonenveloped icosahedral viruses
with an 8 kbp long double-stranded circular DNA
genome. Their genome comprises early genes that
encode E1 and E7 proteins and late genes that encode
L1 and L2 proteins. While the proteins encoded by E1
to E5 form various nonstructural proteins involved in
replication and transcription, the proteins encoded by
E6 and E7 are essential for transformation. L1 and L2
encode virion structural proteins. The proteins encoded
by E6 and E7 are oncoproteins that have been shown to
inhibit cellular tumour suppressor gene products
encoded by p53 and Rb respectively6.
Carcinoma of the cervix is one of the most common
forms of cancers in women and is the second biggest
cause of female cancer mortality worldwide2. The
worldwide incidence is found to be 500,000 per year,
about half of which results in death. Over 80 per cent
of the incidence occurs in developing countries with
25 per cent is estimated to occur in India3,4.
Better methods for prevention and control of
cervical cancer, which would include better hygiene,
early detection through cytology-based screening
programmes and treatment of precancerous lesions,
have substantially reduced the cervical cancer related
death in developed nations. Despite this success, there
are limitations in cervical cancer screening which would
include poor sensitivity of cervical cytology methods,
anxiety and morbidity of screening investigations and
poor uptake by some communities 7 . Hence a
combination approach which includes prophylactic
vaccination and cervical cancer screening may be a
better method to reduce cervical cancer incidence.
Since the first report linking HPV to cervical cancer5,
more than 99 per cent of the cervical cancer cases are
linked to genital infections with HPV, implying the
importance of HPV as a causative agent of this cancer6.
While there are more than 100 genotypes of HPV known,
only 40 of them are found to infect humans. According
to degree of risk of development of cancer, cervical cancer
causing HPV are classified as “high risk” and “low risk”
types. While the low-risk types, which include HPV-6
or HPV-11 and others, cause genital warts, the highrisk types, which include HPV-16, -18, -31, -33, -35, 39, -45, -51, -66 and others, with HPV-16 and -18
accounting for 70 per cent of cases world-wide, cause
cervical cancer. The high-risk type virus infection leads
initially to pre-neoplastic lesions, with majority of them
regress spontaneously. The remaining cases progress to
high-grade lesions, which advance to carcinoma in situ
before progressing to invasive cervical cancer6.
Prophylactic HPV vaccines contain the major capsid
protein L1, which self assemble into virus-like particle
(VLP). These particles are non-infectious as they do not
contain viral genome. Two prophylactic HPV vaccines,
that have been developed recently, have shown excellent
effectiveness against persistent HPV infection and related
cervical lesions among HPV-naive women (i.e. women
who have never been exposed to the virus) aged 16-24
yr, in proof-of-principle studies8-10. Gardasil developed
by Sanofi Pasteur MSD/Merck and Cervarix developed
by GlaxoSmithKline consist of recombinant proteins of
the LI capsid of multiple HPV genotypes which self
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INDIAN J MED RES, JUNE 2008
assemble to form virus like particles (VLPs), combined
with an adjuvant2. Major differences and characteristics
of these two vaccines are summarized in the Table.
Gardasil is a quadrivalent vaccine, which contains the
VLPs for 6 and 11 in addition to VLPs for 16 and 18
prepared with conventional alum adjuvant8,9. Cervarix is
a bivalent vaccine containing VLPs for 16 and 18
combined with a novel adjuvant AS04, containing 3D
monophoryl lipid A (MPL)10.
Some of the important issues to be considered
before implementing the HPV vaccination programme
are (i) age at which vaccination to be given, (ii)
vaccination of men, (iii) co-ordination of screening
programmes, (iv) public education, (v) cost of vaccine,
(vi) cost of distribution of vaccine, and (vii) coverage
of different HPV types.
For the vaccine to be completely effective, it needs
to contain L1 protein against all the most prevalent HPV
types. While the results show both vaccines seem to
provide very high protection against cervical cancer,
the fact that the prevalence of different HPV types vary
substantially between different regions, the impact of
these vaccine may also vary across different parts of
the world2. Although Gardisal is reported to have a
degree of cross-protection against other types, these two
vaccines may not benefit women infected with rare HPV
types. A recent study identified the low frequency of
presence of HPV types 33, 31, 45 and 11, besides the
very high occurrence of HPV 16 and 18 among Indian
women11. Perhaps what is required sooner or later is a
comprehensive study of prevalence of different HPV
types among Indian women and efforts to make an
indigenous multivalent HPV vaccine incorporating L1
proteins of all HPV types that are prevalent in India.
Defining the target population is very important as
these vaccines are effective only in individuals who are
not exposed to HPV. As HPV infection is sexually
transmitted and usually acquired within first few years
of sexual debut, these vaccines are proposed to be given
to girls and women between ages 9 to 25, although the
minimum age at which girls need to be vaccinated in
India may be different. Another possibility is vaccination
of much younger age group (< 9 yr) as it can be easily
incorporated into the existing national immunization
programmes, although trials need to be conducted to find
out the effectiveness of the vaccine in this population.
While the cost of the cervical cancer vaccine is
somewhere between $400 and $500 in US for three
doses, the price in countries like India is not known.
Mechanisms need to be initiated at the Government
levels in consultation with the World Health
Organization to subsidize the cost of manufacturing so
that the vaccine is affordable to girls and women of all
socio-economic status.
There are going to be problems of ethical, religious,
cultural and social nature as the vaccine is against a
sexually transmitted virus. What is needed immediately
is developing appropriate guidelines by the relevant
authorities perhaps with the involvement of the Indian
Council of Medical Research. There is a need to educate
parents of young girls through awareness programmes
about HPV. Proper implementation of vaccination
program with rejuvenated national screening
Table. Comparison of characteristics of cervical cancer vaccines- Gardasil vs. Cervarix
Characteristics
Gardasil
Cervarix
Manufacturer
HPV types
Antigen dose
Adjuvant used
Sanofi Pasteur MSD/Merck
HPV 16, 18, 6 and 11
VLP 16, 18, 6, 11 (40, 20, 20, 40 mg)
Amorphous aluminium hydroxyphosphate
sulphate
0.5 ml intramuscular injection at
0, 2, 6 months
Yeast (Saccharomyces cerevisiae)
Genital warts, cervical dysplasia and cancer
100 per cent
10-20 times natural infection
Well tolerated with no vaccine related
serious adverse events
Harper et al8,9
GlaxoSmithKline
HPV 16 and 18
VLP 16,18 (20, 20 mg)
Amorphous aluminium hydroxyphosphate
sulphate + MPLa (AS04)
0.5 ml intramuscular injection at
0, 1, 6 months
Insect cells (SF9)/Baculovirus
Cervical dysplasia and cancer
100 per cent
50-80 times natural infection
Well tolerated with no vaccine related
serious adverse events
Villa et al10
Dose and schedule
Expression/Production host
Diseases targeted
Immungenicity
Antibody titre
Safety
References
MPL-monophoryl lipid A
SOMASUNDARAM: HPV VACCINE & CERVICAL CANCER
programme is likely to reduce the incidence of cervical
cancer among Indian women.
Acknowledgment
KS is a Wellcome Trust International Senior Research Fellow.
Author thanks Drs Geetashree Mukherjee and Kannan Vaidynathan
for their valuable inputs. Infrastructural support by funding from
ICMR (Center for Advanced studies in Molecular Medicine) to
the Department of Microbiology & Cell Biology, Indian Institute
of Science, Bangalore is acknowledged.
Kumaravel Somasundaram
Department of Microbiology & Cell Biology
Indian Institute of Science
Bangalore 560 012, India
skumar@mcbl.iisc.ernet.in
References
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