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aberrations and malignancies. Furthermore, differences in GLOBAL BURDEN OF HPV IN CANCERS
cell tropism and disease progression patterns are believed AND DISEASES: PREVALENCE AND
to be one of the reasons of higher cancer association with ROLE OF HPV
certain HPV types, such as higher association of HPV18
with adenocarcinoma and in cervical intraepithelial The highest HPV prevalence is observed to be 24% in
neoplasias grade 2 (CIN2). The high risk HPV types Saharan Africa, 21% in Eastern Europe and 16% in Latin
[52]
causing adenocarcinomas may infect cells that already America. In majority of the populations, the highest
have a potential glandular differentiation. Therefore prevalence of HPV is observed in women younger than
[40]
abortive or semipermissive infection of these cells may 25 years. The prevalence reduces in older women with
play an important role in the adenocarcinoma development. some having an increased rate in pri- or early-menopause.
Recently, in silico models and epidemiological studies Although these prevalences are observed for many
showed that the immune response may only contribute less populations, in some others like China, the HPV prevalence
than 20% of HPV clearance in individuals with normal is age-independent. On the other hand, HPV prevalence
immunity. Ryser and colleagues (2015) further proposed remains to be at a constant rate across all age groups in
[41]
[53]
that the virus is mainly cleared by stem cell divisions in countries like Asia and Africa. The reason of different
immunocompromised individuals. [41] prevalences observed in different populations worldwide
are not very well understood, but it is possible that it varies
Overall balance between the positive and negative immune due to the age of initial sexual activity, the number of
factors may vary and these may lead to clearance of partners and the habits of the sexual activities.
lesions. Therefore, therapeutic vaccines against HPV
infections may play a strong role in prevention HPV Different HPV genera cause both non-cancerous and
associated lesions and cancers. In 2006, the Food and cancerous diseases. Formation of warts on the skin and
[42]
Drug Administration approved the use of recombinant uretra, mucous membranes of the oral cavity, respiratory
quadrivalent HPV vaccine gardasil for protection against tract, throat and genitals have been associated with HPV
HPV6, HPV11, HPV16 and HPV18 L1 proteins in females infections. Current data indicates that the prevalences of the
in the age between 9 and 26 years old. It is proposed that genital HPV infections are considerably higher compared
[43]
in three doses of this vaccination at 0, 1 to 2 and 6 months, to the oral HPV. Globally HPV infections are associated
the HPV associated genital warts and the cervical cancer with approximately 50% of HPV caused cancers in women
[54]
can be prevented. This vaccination is also proposed to and 5% in men. Different carcinogenesis is detected
[44]
protect against the vulvar and vaginal cancers as well as at different anatomical sites and at different level that is
intraepithelial neoplasias. In 2009, the bivalent vaccine most likely because of the differences in the expression
[45]
against HPV16 and HPV18 was licensed and this of the viral genome, in such HPV associated genital tract
[46]
vaccine is intended to protect against anogenital warts, infections are observed at higher incidence compared to the
head and neck cancer incidence. Genital HPV infections are
precancerous lesions and cervical cancer. Both the [55]
[45]
bivalent and quadrivalent HPV vaccines have been actively connected with more than 99% of cervical cancers, 97%
[56]
[57]
used in more than 80 countries. Both of the vaccines of anal cancer, 70% of vaginal cancers, 47% of penile
[47]
cancers, 40% of vulval cancers, 47% of oropharynx
[58]
[57]
are shown to be safe, having enduring protection against cancers and 11% of oral cavity cancer cases. [59]
primary infection and stable protection. These vaccines
[48]
have a moderate cross-protection against high risk HPV ROLE OF HPV IN CANCER
types, HPV31, 33, 45, 52 and 58. [49,50] However, only 70% DEVELOPMENT
of cervical cancer cases can be avoided by using these
vaccines. Quadrivalent vaccines also protects against The mechanism of cancer progression in patients with
[51]
low risk HPV types, HPV6 and HPV11 that causes 90% HPV infection is not well established. However, there are
of genital warts. The development of these vaccinations a number of hypothesis on the possible routes of HPV in
[43]
has brought a new era in the prevention of HPV and these cancer progression. One of the hypotheses suggests that
vaccinations are great promise; however there is still the cancer progression is associated with the increased
room for much more development. In general, therapeutic accessibility and proliferation of the basal layers at the
vaccines have been proposed but only few of them reached metaplastic epithelial site and therefore this increases the
clinical trials. The current vaccinations do not protect risk of metastasis. This becomes even more apparent at the
against all the HPV types and the cost of these vaccinations puberty time and the onset of sexual activity. [60]
make them impossible to be used in some parts of the
world, especially in newly developing countries. Therefore, The initial infection of the cell and the relation of this to
although vaccinations enabled a tremendous step towards the disease outcome are not well understood. Generally
prevention of HPV associated diseases, more feasible and HPV infection causes cell destruction as well as cell
affordable vaccinations with protection against all the HPV transformation and tumour development. HPVs interfere
types are required. with cell cycle regulation and prevent apoptosis in cells

Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ June 15, 2016 ¦ 203