INTRODUCTION viral protein causes proteosomal degradation of p53 by

INTRODUCTION

Human papilloma viruses (HPVs) are small non-enveloped DNA viruses, having circular double-stranded DNA genomes, belonging to the papilloma virus family. Over 200 types of HPV have been identi?ed that can cause infection or warts in  mucosal(?-HPV) or cutaneous (?-HPV) surface of the hands, feet, oropharyngeal, and anogenital tracts (1).These infections if persist prolog,  can cause cancers of cervix, vulva, vagina, penis, anus, mouth and throat. HPV genome is  approximately 8 kb in size and subjected into  early(expressed earlier in life cycle of HPV) and late genes(Expressed late)(2).Early proteins (E1-E7), play a role in genome replication, regulation of cellular gene expression, virion assembly, transcription, cell growth and differentiation, apoptosis, regulation and control of cell cycle respectively. Late proteins that includes L1 and L2 proteins  play a role in  capsid formation (3, 4).

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Virus gains entry into their main portal site through  ?6-integrin receptor by  clathrin-mediated endocytosis or through caveolin-mediated endocytosis and gets uncoated. After its transmission to the nucleus, it gets replicated, forming 20-100 copies. HPV is transcribed by one DNA strand utilizing more than one promoter region andyields multiple mRNAs with several open reading frames. The E6/E7  proteins cause inactivation of two tumor suppressor proteins p53 and pRb respectively(5, 6).E6 viral protein causes proteosomal degradation of p53 by utilizing ubiquitin ligase activity of host E6-associated protein, increasing the risk of cancer development. Likewise, in normal conditions, Rb prevents the progression of cells from G1 to S phase of cell cycle by inactivating E2F-DP dimers that are transcription factors of E2F family. But E6/E7 protein inactivates pRb that can result in cancer development(7).

HPV is transmitted by sexual contact with the person affected by HPV but there are other non-sexual ways of transmission of HPV including,

·         Vertical transmission (transmission from father due to infected spermatozoon or from mother via infected oocyte).

·         Perinatal transmission (transmission by direct contact with the infected maternal genital tract or by premature rupture of membrane) and, transmission through breast milk(8, 9).

·         Horizontal modes of transmission of  HPV  involves transmission of virus among sexually unexposed adults, autoinoculation or thorough fomites (10).

Some molecular and non-molecular techniques are available for the detection of HPV. Non-Molecular techniques include Visual inspection by acetic acid or with Lugols’iodine and viewing of the cervix by  illuminated stereoscope (11). Molecular techniques involve Immunological based detection i.e. checking the expression levels of cyclin-dependent kinase inhibitor p16INNK4A ,whose levels gets increased due to E7 protein of HPV. Mostly Hybrid CaptureTM version and PCR based methods are being used for HPV detection.

Currently there is not a single treatment available for HPV but prevention can be assured by using vaccines. Vaccines against HPV 16 and 18 are being used in many countries. Two types of vaccines are being used including Prophylactic vaccines that produce antibodies against capsid proteins L1 and L2 and therapeutic vaccines that have neutralizing effect against non-structural early viral antigens e.g.E6 and E7.Therapeutic vaccines are considered more authentic as compared to Prophylactic vaccines because  some cells like basal keratinocytes don’t express L1 or L2(12).

HPV infections are increasingly becoming prevalent. Lack of medication and broad spectrum vaccination is making disease management difficult. Certain regions of world specially Africa and America have highest mortality rates due to lack of knowledge in sexual education. In about80% of cases, co-infection of HPV along with HIV have been reported in various studies and more information is required regarding propagation and incidence of HPV virus.

The current study aims at mapping the most prevalent HPV genotypes worldwide with the incidence rate of certain types of cancers including vulvar, vaginal and most importantly cervical cancer. A precise meta-analysis of HPV virus along with its outbreak, incidence, mortality rates and reported cases are also discussed in detail in this review.