world cancer report - iarc

Fig. 4.23 Proteins which make up the HPV particle
are used in the manufacture of a vaccine.
Fig. 4.24 Collecting blood from a participant in an
HPV prevalence study, Ibadan, Nigeria.
regression of HPV-associated lesions. The
E6 and E7 proteins (Oncogenes and
tumour suppressor genes, p96) are the
natural targets for these vaccines because
such proteins are consistently expressed
in cervical cancer cells. Since neither protein
is located on the cell surface, the
most effective mechanism for the
destruction of cancer cells is likely to be
through the action of cytotoxic T cells
which recognize intracellular processed
peptides in complex with major histocompatibility
complex (MHC) class I molecules.
Candidate therapeutic vaccines are
constituted using either synthetic peptides,
recombinant proteins or live vectors
coding for HPV proteins [8].
Several vaccines that target the E6 and E7
oncoproteins of HPV 16 and 18 are now
available and are being used in phase I-II
trials (Table 4.11). These trials have been,
or are being carried out in patients with
advanced cervical cancer or in patients
with genital precancerous lesions. Some
of the vaccines are peptide-based while
others are based on a recombinant vaccinia
vector expressing E6 and E7 from
both HPV 16 and 18 [9]. Results from only
one of these trials have been published in
full [10]. As is the case for prophylactic
HPV vaccines, in order to develop safe and
Organization HPV type and Vaccine type Current status
(vaccine name) antigen
Medimmune SmithKline HPV-11 L1 VLP Phase II trials under way;
Beecham safety and immune
(MEDI-501) response proven in
Phase I trials
Medimmune SmithKline HPV-16, 18 L1 VLP Phase II trials under way
Beecham
(MEDI-503, 504)
Merck, CSL Limited HPV-16 L1 VLP Phase II trials under way
in USA, UK and Australia;
Phase III to begin soon
National Cancer Institute, HPV-16 L1 VLP Phase II trials under way;
NIAID large-scale efficacy trial
planned to begin in
Costa Rica in 2002
Medigene HPV16 L1, E7 VLP Phase I/II trial
Table 4.9 Prophylactic HPV vaccines under development in clinical trials. VLP = virus-like particles
effective therapeutic vaccines, serious
technical difficulties must be overcome.
Such vaccines must be tailored to the
MHC antigens of the recipients and must
elicit a stronger anti-tumour response
than that produced without vaccination.
Combined or chimeric vaccines are
designed to have the ability to both protect
against HPV infection and induce
regression of HPV-associated lesions [8].
The first approach considered was to
develop an L1 or L1-L2 VLP-based vaccine
capable of inducing a cytotoxic T-cell
response. Another approach being used is
the production of chimeric VLPs that con-
Issue Comments
Table 4.10 Open issues in the development of prophylactic HPV vaccines.
tains both L1 or L1-L2 and E6 or E7 proteins
[9]. Such vaccines should induce a
protective response elicited by L1 or L2
proteins and a cytotoxic T cell-mediated
response elicited by the E6 or E7 proteins.
There are still many technical and practical
problems to be solved before safe,
effective and inexpensive HPV vaccines
are produced for mass use in the general
population. Although these problems
appear to be greater for therapeutic vaccines,
their production has moved into an
industrial phase. Lessons learnt from the
slow introduction of hepatitis B virus vaccine
into routine immunization pro-
HPV types to be included At least 30 oncogenic types exist, but HPV 16
accounts for 50% and HPV 18, 31, and 45 together for
a further 30% of cervical cancers
Route of administration Oral or nasal spray
Target population Ideally infants, girls and boys
Cost It should be low, perhaps using bacterial vectors or
transgenic plants
Human papillomavirus vaccination 149