1. P APOVAVIRUS FAMILY (P APOVAVIRIDAE ) : NOW 2 F AMILIES Papillomaviruses and Polyomaviruses

2. H UMAN PAPILLOMAVIRUSES (HPV S ): Warts human cancer (e.g., cervical carcinoma ): several genotypes

3. P OLYOMAVIRIDAE BK and JC viruses, usually asymptomatic infection in immunosuppressed people : BK: renal disease JC: progressive multifocal leukoencephalopathy ( PML ), Simian virus 40 ( SV40 )

4. U NIQUE P ROPERTIES OF P OLYOMAVIRUSES AND P APILLOMAVIRUSES Small Double-stranded circular DNA genome

5. U NIQUE P ROPERTIES OF P OLYOMAVIRUSES AND P APILLOMAVIRUSES Viruses encode proteins that promote cell growth These proteins bind to the cellular growth-suppressor proteins p53 and p105RB (p105 retinoblastoma gene product). Papilloma E6 binds to p53, and Papilloma E7 binds to p105RB

6. U NIQUE P ROPERTIES OF P OLYOMAVIRUSES AND P APILLOMAVIRUSES lytic infections Persistent latent infections immortalize ( transform ) cells

7. H UMAN P APILLOMAVIRUSES (HPV) More than 100 genotypes HPV can be distinguished further as cutaneous HPV or mucosal HPV on the basis of the susceptible tissue. Within the mucosal HPV, there is a group associated with cervical cancer.

8. HPV infect and replicate in the squamous epithelium of skin ( warts ) and mucous membranes ( genital, oral, and conjunctival papillomas ) to induce epithelial proliferation.

9. TRANSMISSION HPV resists inactivation can be transmitted on fomites, such as the surfaces of countertops or furniture, bathroom floors, and towels Asymptomatic shedding may promote transmission.

10. TRANSMISSION HPV infection is acquired (1) by direct contact through small breaks in the skin or mucosa (2) during sexual intercourse (3) while an infant is passing through an infected birth canal.

11. D ISEASE M ECHANISMS OF P APILLOMAVIRUSES AND P OLYOMAVIRUSES P APILLOMAVIRUSES Virus is acquired by close contact and infects the epithelial cells of the skin or mucous membranes. Tissue tropism and disease presentation depend on the papillomavirus type. Virus persists in the basal layer and then produces virus in terminally differentiated keratinocytes. Viruses cause benign outgrowth of cells into warts.

12. D ISEASE M ECHANISMS OF P APILLOMAVIRUSES AND P OLYOMAVIRUSES P APILLOMAVIRUSES HPV infection is hidden from immune responses and persists. Warts resolve spontaneously, possibly as a result of immune response. Certain types are associated with dysplasia that may become cancerous with the action of cofactors. DNA of specific HPV types is present (integrated) in the tumor cell chromosomes.

13. P OLYOMAVIRUSES (JC AND BK V IRUSES ) Virus is probably acquired through the respiratory route and spread by viremia to the kidneys early in life. Infections are asymptomatic. Virus establishes persistent and latent infection in organs such as the kidneys and lungs.

14. P OLYOMAVIRUSES (JC AND BK V IRUSES ) In immunocompromised people, BK: Renal infection(hematuri) JC virus is activated, spreads to the brain, and causes progressive multifocal leukoencephalopathy ( PML ), a conventional slow virus disease.

15. E PIDEMIOLOGY OF P OLYOMAVIRUSES AND P APILLOMAVIRUSES Disease/Viral Factors Capsid virus is resistant to inactivation Virus persists in host Asymptomatic shedding is likely Transmission Papillomavirus: direct contact, sexual contact (sexually transmitted disease) for certain virus types, or passage through infected birth canal for laryngeal papillomas (types 6 and 11) Polyomavirus: inhalation or contact with contaminated water

16. E PIDEMIOLOGY OF P OLYOMAVIRUSES AND P APILLOMAVIRUSES Who Is at Risk? Papillomavirus: warts are common; sexually active people are at risk for infection with HPV types correlated with oral and genital cancers Polyomavirus: ubiquitous; immunocompromised people

17. H UMAN PAPILLOMAVIRUS is possibly the most prevalent sexually transmitted infection in the world, with certain HPV types common among sexually active people. At least 20 million people in the United States are infected with HPV, with approximately 6 million new genital cases per year.

18. HPV HPV is present in 99.7% of all cervical cancers. HPV-16, HPV-18, HPV-31, and HPV-45 are high-risk the second leading cause of cancer death in women

19. HPV 10% of women infected with the high-risk HPV types will develop cervical dysplasia, a precancerous state. Major risk factors for infection and progression to cancer: Multiple sexual partners smoking a family history of cervical cancer immunosuppression

20. HPV DISEASES Cutaneous Syndromes Skin warts Mucosal Syndromes Benign head and neck tumors Laryngeal papilloma Oral papilloma Conjunctival papilloma Anogenital warts Condyloma acuminatum 6, 11 Cervical intraepithelial neoplasia, cancer16, 18

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25. L ABORATORY D IAGNOSIS OF P APILLOMAVIRUS I NFECTIONS Cytology:PAP smear:Koilocytotic cells Polymerase chain reaction Viral nucleic acid

26. K OILOCYTES characteristic of papillomavirus infection, are enlarged keratinocytes with clear haloes around shrunken nuclei

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28. V ACCINE : Vaccine: http://www.cdc.gov/hpv/http://www.cdc.gov/hpv/ tetravalent HPV vaccine (Gardasil) :HPV 6, 11, 16, and 18 can prevent infection and hence reduce the incidence of anogenital warts and cervical cancer. Bivalent HPV(Cervarix)(16,18) A series of three immunizations is recommended for girls ( boys), starting at age 11 prior to sexual activity.

29. V ACCINE The HPV vaccine is not a replacement for a PAP smear, and women should continue to be tested. At present, the best way to prevent transmission of warts is to avoid coming in direct contact with infected tissue. Proper precautions (e.g., the use of condoms) can prevent the sexual transmission of HPV!!!!