HPV Virology Lectures PDF

# Human Papilloma Virus (HPV) ## Prof. Julius Oyugi, PhD Department of Medical Microbiology Virology lectures ## What is Human Papilloma Virus (HPV)? - HPV belongs to the family of viruses known as Papovaviridae, which was named for it's three main members: Papillomavirus, Polyomavirus, and simia...

# Human Papilloma Virus (HPV) ## Prof. Julius Oyugi, PhD Department of Medical Microbiology Virology lectures ## What is Human Papilloma Virus (HPV)? - HPV belongs to the family of viruses known as Papovaviridae, which was named for it's three main members: Papillomavirus, Polyomavirus, and simian Vacuolating Agent. - The family contains two genera of oncogenic viruses, Papilloma and Polyoma viruses. - Papillomaviruses are small DNA viruses. The DNA genome is comprised of six early (E1, E2, E4, E5, E6, E7) two late (L1 and L2) proteins. - They are non-enveloped, icosahedra particles. ## HPV16 Genome - Many of the HPV genomes have been sequenced and have a genetic organization similar to that of HPV-16, one of the oncogenic strains. - **Early (E) and late (L)** - Early genes control transcription, DNA replication, transformation - Late genes = capsid proteins ## Functions of Viral Proteins ### E2 Protein - Integration of the HPV genome in the host cell chromosome usually disrupts E2 expression, causing a deregulated expression of E6 and E7, and this event can favor the transformation of human cells and the transition into a malignant state. ### E6 Protein - Has the ability to bind and degrade the tumor suppressor protein p53, through the recruitment of the E6-associated protein. - The E6 protein can overcome the cell arrest and proapoptotic activities of p53 by targeting p53 for degradation. ### E7 Protein - It will induce cellular proliferation by binding to several cellular factors. The best characterized of these interactions is with the Retinoblastoma (RB) Tumor Suppressor ## What do we know about HPV? - HPV a group of more than 150 related viruses. - 40 of which cause genital infection. - HPV is the most common sexually transmitted infection. - HPV infection is more prevalent in young adults than in the elderly. - Most infections are self-limited and are asymptomatic. - Some HPVs can cause genital warts and considered low risk. - Other types can cause cancer and are considered high risk. - **4 common subtypes** - “high risk” 16 and 18 (oncovirus) - “low risk” 6 and 11 (benign) - The prevalence of HPV is nearly 80% in adults globally. - HPV-16 and 18 responsible for 70% of all cervical cancers worldwide - HPV-6 and 11 responsible for 90% of genital warts. ## Transmission - Anyone who has ever had a sexual encounter, even without penetration, can contract HPV. - Most common transmission is by skin-to-skin contact with the penis, scrotum, vagina, vulva, or anus of an infected person. - Kissing or touching a partner's genitals with the mouth can also transmit the HPV virus. - **Skin-skin contact** - Genital-genital - Manual-genital - Oral-genital - Does not require penile vaginal sexual intercourse - Condoms of uncertain effectiveness. ## Risk Factors for - **HPV infection are similar to other STI** - lower SES, concurrent STI (including other strains of HPV), # sexual partners. - **HPV-induced cervical cancer include** early age sexual debut, smoking, high parity, long-term use of estrogen, HIV. ## How Does HPV “Cause” Cancer? - In 1995, a study on Cervical Cancer was reported by the International Biological where more than 1,000 specimens of invasive cervical cancer were tested for the presence of HPV via a polymerase chain reaction-based assay and found that: - HPV DNA was present in 93% of the tumors, with no difference in presence across the 22 participating countries. - HPV-16 was present in 50% of specimens. - The other strains present included 18, 45, 31, 39 and 59 in descending order of prevalence. ## High-Risk HPV strains and cancer: HPV 16, 18, 31, 39, 45 and 59: - Protein E6 interacts with p53 in the host cell and promotes its degradation via the ubiquitin dependent pathway. - Protein E7 complexes with retinoblastoma protein (Rb), thereby inactivating it. - Rb and p53 are both tumor suppressors, involved in DNA repair and cell death. ## Natural History Of Cervical HPV Infections - A diagram is shown with two sections labelled Transient Infection and Persistent HPV Infection. - Transient infection shows the movement of HPV from initial infection to infected cervix and the normal process of clearance. - Persistent HPV Infection shows a progression from HPV infected cervix to precancerous lesions and finally to cancer. ## HPV Disease- Genital Warts - Genital warts: - Are skin growths, that are usually fairly small and rough. - In women, genital warts often appear: - On the vulva. - In or around the vagina. - In or around the anus. - On the groin. - On the cervix. ## HPV Disease - Cancers - HPV is associated with several cancers: - Cancers of the cervix, vagina, penile, anal oropharyngeal. ## Testing and Diagnosis - Pap smear recommended every 6 mo - 3 yrs for all women post-puberty (High false negative rate) - Colposcopy, acetic acid. - Molecular tests for viral DNA (Very sensitive) - An estimated 2% of women in Kenya are getting regular Pap tests every 3 years (4% in Nairobi) ## Treatment HPV/ Cancer - HPV most often cleared by immune system, no antiviral recommended. - CIN2-3 are treated by removal: - Freezing - Laser - Surgically - Radical hysterectomy, chemotherapy, radiotherapy - Immunotherapies: - E6 and E7 protein immunizations ## Prevention - Reducing the number of sex partners: - Abstinence - Long-term mutual monogamy with a single uninfected partner. - A reduced number of partners with partners not likely to be infected. ## Vaccination - Two vaccines are currently used, Gardasil and Cervarix for prevention of cervical cancer. - Both vaccines protect against two of the HPV types (HPV-16 and HPV-18) that can case cervical cancer and some other genital cancers. - Gardasil and Cervarix are preventative vaccines and do not treat HPV infection or cervical cancer. - They are recommended for women who are 9 to 25 years old who have not been exposed to HPV.