HUMAN PAPILLOMA VIRUS INFECTION &

CERVICAL CANCER

SUBMITTED BY

ABHIJIT BANIKDEPT. OF HUMAN PHYSIOLOGY WITH COMMUNITY HEALTH

VIDYASAGAR UNIVERSITYMIDNAPORE, WEST BENGAL,INDIA

WHAT IS CERVICAL CANCER?

Cervical cancer is a malignant neoplasm arising from cells originating in the cervix uteri

Cervical cancers are squamous cell carcinomas, arising in the squamous (flattened) epithelial cells that line the cervix

EPIDEMOLOGY OF CERVICAL CANCERCervical cancer is the second most common cancer in women worldwide and in women in developing countries In women younger than 40 years, HPV was present in 89% of adenocarcinomas, whereas in women aged 60 years and older, HPV was observed in only 43%Every year, 470,000 new cases of cervical cancer are diagnosed worldwide, and about half of the afflicted women will die

It affects about 16 per 100,000 women per year and kills about 9 per 100,000 per year

Approximately 80% of cervical cancers occur in developing countries

Worldwide, in 2008, it was estimated that there were 473,000 cases of cervical cancer and in 2010 225,000 deaths

CERVICAL CANCER SUBTYPESSquamous

cell carcinoma (about 80-

85%) Adenocarcinoma (about

15% )

Adenosquamous carcinoma

Small cell carcinoma

Neuroendocrine tumors

Glassy cell carcinoma

Villoglandular adenocarcinoma

CHANGES IN CERVICAL CANCER

NORMAL ENDOCERVICAL CELL MALIGNANT ENDOCERVICAL CELL Fig.-CHANGES IN ADENOCARCINOMA

NORMAL CERVICAL CELL MALIGNANT SQUAMOUS CELL Fig.- CHANGES IN SQUAMOUS CELL CARCINOMA

SIGNS & SYMPTOMS OF CERVICAL CANCER The early stages of cervical cancer may be completely asymptomatic Vaginal bleeding, contact bleeding, or (rarely) a vaginal mass may indicate the presence

of malignancy Moderate pain during sexual intercourse and vaginal discharge are symptoms of

cervical cancer

In advanced disease, metastases may be present in the abdomen, lungs or elsewhere

VAGINAL BLEEDING

Symptoms of Advanced Cervical Cancer

Loss of appetite

Weight loss

FatiguePelvic pain, back pain,

leg painSwollen legs

Heavy bleeding from the vagina

Bone fractures Leakage of urine or

faeces from the vagina

RISK FACTORS OF CERVICAL CANCER

SmokingUse of oral contraceptivesMultiple pregnanciesA weakened immune system caused by HIVUse of immunosuppressing drugs

HUMAN PAPILLOMA VIRUS Human papillomavirus (HPV) is a name of group of DNA virus from the

Papovaviridae family that is capable of infecting humans Papillomaviruses are small ,nonenveloped viruses with 55-nm-diameter icosahedral

capsids composed of 72 capsomers, which contain at least two capsid proteins, L1 (major) and L2 (minor)

Each capsomer is a pentamer of the major capsid protein HPV genome consists of a single molecule of double-stranded, circular DNA

containing approximately 7.900 bp associated with histones

Fig.-STRUCTURE OF HUMAN PAPILLOMA VIRUS

VIROLOGY

The genome is functionally divided into three regions-

a) noncoding upstream regulatory region (URR)

b) “Early” region

c) “Late” region The URR region contains the p97 core promoter along with enhancer and silencer

sequences that regulate DNA replication by controlling the transcription of the “early” and “late” regions

The URR region also contains the highest degree of variation in the viral genome The “early” region, which include the genes E1, E2, E3, E4, E5, E6, E7 and E8. This

region is involved in viral replication and oncogenesis The “late” region, which encodes the L1 and L2 structural proteins for the viral capsid

HPV & HUMAN DISEASE

Approximately 200 different HPVs have now been characterized basis of DNA sequence

Among each HPV groups, individual viruses are designated high risk or low risk according to the propensity for malignant progression of the lesions that they cause

Low-risk HPV types include types 6, 11, 42, 43, and 44, and usually cause benign anogenital warts

High-risk HPV types include types 16, 18, 31, 33, 34, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68 and 70, and cause anogenital cancer

Human cervical cancers are associated with high-risk HPV infections

HPV STRAINS RESPONSIBLE FOR CERVICAL CANCERHigh-risk oncogenic HPV types (including HPV 16 & HPV 18) are responsible for approximately 75% of all cases of cervical cancer

HPV strains, HPV 31 and HPV 45 are the cause of another 10%

PATHOGENESIS OF HPV INFECTION Transmission of HPV occurs primarily by skin-to-skin contact Basal cells of stratified squamous epithelium may be infected by HPV HPV infection of the basal layer requires mild abrasion or micro trauma of the

epidermis HPV establishes itself as a low-copy- number episome by using the host DNA

replication machinery to synthesize its DNA on average once per cell cycle

The Molecular Mechanisms of Oncogenic HPV Infection HPV-induced carcinogenesis is the integration of the HPV genome into a host chromosome The two primary oncoproteins of high risk HPV types are E6 and E7 The function of the E6 and E7 products during a productive HPV infection is to subvert the

cell growth-regulatory pathways The E6 and E7 gene products deregulate the host cell growth cycle by binding and

inactivating two tumor suppressor proteins: the tumor suppressor protein (p53) and the retinoblastoma gene product (pRb)

The HPV E6 gene product binds to p53 and targets it for rapid degradation The HPV E7 gene product binds to pRb and this binding disrupts the complex between pRb

and the cellular transcription factor E2F-1 The inactivation of p53 and pRb proteins can give rise to an increased proliferation rate and

genomic instability

continued…

As a consequence, the host cell accumulates more and more damage DNA that cannot be repaired, leading to transformed cancerous cells

In addition to the effects of activated oncogenes and chromosome instability, potential mechanisms contributing to transformation include methylation of viral and cellular DNA, telomerase activation and hormonal and immunogenetic factors

Fig.- Molecular mechanisms of oncogenic HPV infection

TREATMENT & PREVENTION OF HPV INFECTION Two prophylactic vaccines have been developed ; Gardasil(HPV4) and

Cervarix(HPV2) Gardasil is a quadrivalent vaccine, protecting against four types of HPV – 16, 18, 6 and

11 Cervarix is bivalent and protects against HPV types 16 and 18 Both vaccines are supplied as a liquid in a single dose vial or syringe Neither vaccine contains an antibiotic or a preservative

Good health is closer than ever

THANK YOU