Vaccine for Human Papillomavirus

Review Article

Austin J Clin Immunol. 2016; 3(1):1027.

Vaccine for Human Papillomavirus

Getinet Melkamu*, Gelaw Baye and Assefa Abate

Department of Medical Microbiology, University of Gondar, Ethiopia

*Corresponding author: Getinet Melkamu, Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia

Received: January 08, 2016; Accepted: January 30, 2016; Published: February 02, 2016


Human Papillomavirus (HPV) is among the large group of epitheliotropic viruses with more than 100 different types. There are about 40 HPV types infecting the human body with the association of oncogenic risk. The development of cervical cancer is contributed by a variety of factors even though HPV is the primary etiologic agent. Cervical cancer is the second most common cancer among women in the developing countries and estimated to affect approximately 500 000 women worldwide each year, of whom 80% live in developing countries. All cervical cancer cases are resulted from genital infection of HPV and shared similar risk factors with Human Immunodeficiency Virus (HIV).

There is no effective treatment for HPV infections and immunization against HPV may be paramount important to prevent this infection. The main aim of this review is to compile data on HPV vaccinations. Vaccination of target groups is indispensable aspect of HPV prevention. The two currently available HPV vaccines, Gardasil and Cervarix are designed to protect against four types of HPV. Each of them produce Virus Like Particles (VLPs) prepared from recombinant vaccine technology. These vaccines are most effective during childhood or adolescence, but adults also can be benefited. The HPV vaccine is highly immunogenic have the ability to circumvent the viral immune evading mechanisms. The vaccine has no serious side effects, targeted for reproductive age groups, highly efficacious in preventing new infections of most common oncogenic HPV types and will dramatically reduce the rates of HPV associated cancer. The vaccine is widely and properly delivered to the target population particularly for developing countries. So feature researches should be focus on the introduction of HPV vaccines in to routine immunization.

Keywords: Human papillomavirus; HPV vaccine


The papillomaviruses are members of the family Papovaviridae, non enveloped and double strand Deoxy ribonucleic Acid (DNA) virus [1]. Papillomaviruses can infect humans as well as animals. Papillomaviruses that infect humans are known as human papillomavirus. The HPV usually causes a variety of benign papillomatous lesions of the skin, squamous mucosa and induces tumors in their natural host [2].

Human papillomavirus is among the large group of epitheliotropic viruses of more than 100 different types, 40 are known to cause infections to humans. Some of them are associated with oncogenic risk [3]. Based on their oncogenic potential genital HPV can be classified in to Low-Risk (LR) and High-Risk (HR) genotypes. The HPV 16 and 18 are among the HR types and responsible for the majority of HPV associated cancers of the ano-genital tract, while HPV 6 and 11 are the LR types which cause a substantial proportion of low-grade cervical dysplasia. More than 90% of genital warts are also due to LR types. On the other hand 99% of cervical cancer is due to HR types [4].

Though, HPV is the primary etiologic agents of cervical cancer, variety of factors contribute for the development of cervical cancer. Several studies revealed that HIV infection in women is associated with an increased risk of HPV associated malignancies and cervical cancer [5]. Different findings also strongly support a dose response relationship between host immune status and the risk of HPV-related tumorigenesis [6]. The HIV-positive women have a higher prevalence of cervical epithelial cell abnormality and high progression rate of precancerous cervical lesions [7]. Cervical cancer is the aggravation factor for the progression of HIV and vice versa [8]. HIV treatment guidelines recommend annual Pap tests for HIV infected women [9].

Women who acquire HPV infection do not develop invasive cancer. Most infections are transient and approximately 90% of infections clear within 2 years [10]. The peak prevalence of HPV infection occurs in the late teens and early twenties following onset of sexual activity [11], that can be easily spread through direct skinto- skin contact during vaginal, anal and oral sex [12]. In fact, more than half of sexually active people are infected with one or more HPV types at some point in their lives [13]. The HPV infection is mainly squamous epithelial cell surfaces of skin or mucosa, such as the interior mouth, throat, tongue, tonsils, vagina, cervix, vulva, penis, and anus. Infection is initiated when infectious particles binds with basal layer of the epithelium. Since, HPV infection is more of asymptomatic and its persistence nature, infected people do not know they have it [14,15].

The presence of HPV infection can be detected by using screening methods based on epithelial abnormality or DNA testing technologies [16]. Infection with HPV leads in to other complications like infertility [17]. Cervical cancer is the second most common cancer among women in the developing countries and estimated to affect approximately 500 000 women worldwide each year, of whom around 80% of cases occur in developing countries. Moreover, all cervical cancer cases are as a result of genital HPV infection [18].

Understanding the existence and transmission of HPV are indispensable aspects of its prevention. Poor comprehensive knowledge about cervical cancer, associated risk factors and cost incurred for cervical cancer cases were assessed in Gondar and Tikur Anbessa hospital respectively. The result revealed that poor knowledge and high cost incurred per patient (cost per patient was $407.20) were identified [19,20].

Infections associated with HPV are not treated; treatment option is directed on the lesions of genital warts, cervical, vaginal, and vulvar cancer precursors are by applying local approaches like:- cryotherapy, electrocautery, laser therapy, and surgical excision. These treatments can reduce the infectiousness but not eliminate HPV [21]. The HPV infections also largely shielded from the host immune response because they are restricted to the epithelium. The best characterized and most type-specific antibodies are those directed against conformational epitopes of the L1 capsid protein assembled as VLPs [22].

Immunization against HPV may have greatest value in developing countries, where 80% of the global burden of cervical cancer occurs each year and where Pap screening programs are not practice. Two types of prophylactic vaccine are currently being developed [23]. Vaccine safety and efficacy are some of the advantages. On the other hand the vaccine has some disadvantages like: it doesn’t prevent all strains, little is known about long term effects and it has few side effects [24]. The aim of this review was to summarize various aspects of immunity against HPV and the use of vaccine.

Immune response against HPV

Transient genital HPV infections are relatively common in young sexually active women but most of these infections are subclinical and spontaneously resolve [25]. Of the HPV-infected women who develop persistent infections, only a few will progress to ICC. Natural immune response is adequate to clear disseminated HPV infection. Although the natural immunity is responsible to clear the infection, the mechanisms of actions are largely undefined. Different studies implicate the involvement of both innate and adaptive immunity. The human female reproductive tract has the capacity to mount both humoral immunity and Cell Mediated Immunity (CMI) following infection with HPV [26].

The role of innate immune system during early stages of HPV infections creates a pro-inflammatory microenvironment. This is due to the recruiting of innate immune cells to eliminate the infected cells and initiating an effective acquired immune response [27]. Most benign lesions mount an effective CMI and the lesions regress by a CD4+ T cell dominated T helper (Th) 1 response. The central role of the CD4+ T cells can be demonstrated, when an increased prevalence of HPV infections in immunocompromised individuals [26]. Keratinocytes the cells infected by HR HPV are equipped with different Pattern Recognition Receptors (PRRs). This allows to recognize invading pathogens and to activate the immune system [27]. Serum neutralizing antibody to the major capsid protein L1 usually develops after the induction of successful CMI. These antibody and cell mediated responses are protective against subsequent viral challenge in natural infections [26].

However, HPV has a wide range of strategies for evading immune response. It can generate anti-inflammatory microenvironment to down-regulate adhesion molecules and chemo-attractants [27]. The persistent nature of HPV infection is also an effective evasion mechanism of innate immunity [28]. More over HPV develop induced expression of the cellular protein like Ubiquitin Carboxyl- Terminal Hydrolase L1 (UCHL1) in keratinocytes to suppresses the activation of signals and downstream of the pathogen receptor. As a result transcription factor activation and gene expression of HPV are reduced, in particular pro-inflammatory cytokine and lowers the attraction of immune cells and thereby the chance of HPV-infected cells to be recognized and eliminated and as such enables HPV to persist [26].

Several studies shown that HR HPV infection also down regulate IFN-α inducible gene expression. The HPV 16 E6 and E7 oncoproteins directly interact with components of the interferon signaling pathways, even in the absence of viral-induced cytolysis and cell death. The type 1IFNs (INF-α and β) is powerful, generic and innate antiviral defense system. The antiviral effects of IFNs have anti proliferative and immuno stimulatory properties that act as a bridge between innate and adaptive immunity [29]. Human papillomavirus is also able to inhibit the secretion of Interferon gamma (IFN-γ) and the expression of some innate immune cell receptors like NKs. Immunoglobulin-Like Transcript 2 (ILT2) is regulatory receptors that participate in the pathogenesis of viral infections [30]. T-cell responses to E2, E6 and E7 are lost or reduced in HSIL and invasive carcinoma. Even if HPV antigen-specific cytotoxic T-cells are released, the regulatory T-cells increasingly dominate the lesions and reduce the killer defense response. The challenge for therapeutic vaccines for HPV associated disease is to reverse this immunologically suppressive microenvironment and allow the cytotoxic killers to access the infected cells [28]. The overall innate immune response is summarized in Figure 1.