Vaccines against human papillomavirus in low and middle income countries: a review of safety, immunogenicity and efficacy
Nakalembe et al. Infectious Agents and Cancer
Vaccines against human papillomavirus in low and middle income countries: a review of safety, immunogenicity and efficacy
Miriam Nakalembe 0
Florence M. Mirembe 0
Cecily Banura 1
0 Department of Obstetrics and Gynaecology, Makerere University , Kampala , Uganda
1 Department of Child Health and Development Center, Makerere University , Kampala , Uganda
Currently, there is limited data on the immunogenicity and efficacy of human papillomavirus vaccines in Low and Middle income countries (LMIC). The review aims to summarize the current status from published HPV vaccine safety, immunogenicity and efficacy studies in low and middle income countries (LMIC). Electronic databases (PubMed/MEDLINE and HINARI) were searched for peer reviewed English language articles on HPV vaccination in LMIC that have so far been published from 1st January 2006 up to 30th January 2015. Eligible studies were included if they had used the bivalent (bHPV) or quadrivalent HPV (qHPV) vaccines in a LMIC and investigated safety, immunogenicity and/or efficacy. The main findings were extracted and summarized. A total of fourteen HPV vaccine studies assessing safety, Immunogenicity and efficacy of the bivalent or quadrivalent vaccines in LMIC were included. There are only ten published clinical trials where a LMIC has participated. There was no published study so far that assessed efficacy of the HPV vaccines in Sub-Saharan Africa. From these studies, vaccine induced immune response was comparable to that from results of HICs for all age groups. Studies assessing HPV vaccine efficacy of the bivalent or quadrivalent vaccine within LMIC were largely missing. Only three studies were found where a LMIC was part of a multi center clinical trial. In all the studies, there were no vaccine related serious adverse events. The findings from the only study that investigated less than three doses of the bivalent HPV-16/18 vaccine suggest that even with less than three doses, antibody levels were still comparable with older women where efficacy has been proven. The few studies from LMIC in this review had comparable safety, Immunogenicity and efficacy profiles like in HIC. Overall, the LMIC of Africa where immune compromising/modulating situations are prevalent, there is need for long term immunogenicity as well as surveillance studies for long term clinical effectiveness after two and three dose regimens.
Human papillomavirus vaccines; Immunogenicity; Safety; Efficacy; Low middle income countries
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Background
Globally, cervical cancer is the 3rd most common
malignancy among women with more than 530,000 incident
cases and over 275,000 deaths annually [1]. The greatest
burden of disease (over 85 %) occurs in the LMIC where
there is lack of or limited organized screening and treatment
programs that are present in the high income countries [2].
Human Papilloma Virus (HPV), the most common
sexually transmitted infection has been recognized as a
necessary cause of cervical cancer [3]. There are over
100 types of HPV genotypes, with HPV types 16 and 18
being responsible for approximately 70 % of cervical
cancers worldwide, and types 6 and 11 for 96–100 % of
genital warts infections [4]. Besides cervical cancer,
certain HPV types are also associated with a proportion
of cancers of the anus, oropharynx, the vulva, vagina
and the penis which may too be impacted by the HPV
vaccines [5]. However, the incidence rates of these cancers
are much lower (e.g., estimated global incidence for anal
cancer is 1 per 100,000 with 27,000cases per year), [5]
than that of cervical cancer and the HPV vaccines impact
on their incidence remains to be known.
Prophylactic vaccines are composed of virus like particles
made with synthetic L1 proteins derived from HPV 6, 11,
16 and 18 that assemble together to form an empty
viruslike capsid. The bivalent (Cervarix™) that protects against
HPV 16 and 18 and the quadrivalent (Gardasil™) that
protects against HPV 6, 11, 16 & 18 have been approved
in 2007 and 2009, respectively [6, 7]. Both vaccines protect
against infections and lesions induced by the HPV vaccine
types, provided that the recipient has not been exposed to
these HPV types before vaccination. Availability of the
prophylactic human papillomavirus (HPV) vaccine is seen
as a key strategy in reducing the burden of cervical cancer
in low and middle income countries (LMIC) where this
has so far been unachievable [8].
To date, at least 110 countries have licensed the bivalent
HPV vaccine and over 120 countries have licensed the
quadrivalent vaccine [9]. However, despite the licensure,
about 51 countries worldwide have incorporated the
vaccine in their National vaccination programs and
only six countries are LMIC (85 countries comprise
LMIC as per World Bank list (July 2014) [10]. WHO
recognizes the global importance of preventing cervical
cancer and HPV-related diseases and therefore
recommends that HPV immunization should be part (...truncated)