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Papilloma and Polyoma (2010)

Papilloma and Polyoma (2010)

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Published by: Angeline Buton on Oct 07, 2011
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PAPILLOMAVIRUSES AND POLYOMAVIRUSES

Maria Cielo B. Malijan, MD, DPPS, FPSDBP

PAPOVAVIRIDAE
• Family no longer exists
PAPOVAVIRIDAE

• POLYOMA AND PAPILLOMAVIRUSES

• SIMILARITIES:
• Morphology • Nucleic composition • Transforming capabilities

PAPILLOMAVIRIDAE

POLYOMAVIRIDAE

• DIFFERENCES
• biology • genome organization

PAPILLOMAVIRIDAE

PAPILLOMAVIRIDAE
• • • • • Virion: Composition: Genome: Proteins: Envelope:
– – – –

Icosahedral, 55nm in diameter DNA (10%), Protein (90%) dsDNA, circular, 8kbp
2 structural proteins, cellular histones condense DNA in virion

none

• Outstanding characteristics:
Stimulate cell DNA synthesis Restricted host range and tissue tropism Significant cause of human cancer, especially cervical cancer Viral oncoproteins interact with cellular tumor suppressor proteins

.Papilloma virus All 72 capsomeres are pentamers of the major structural protein.

PAPILLOMAVIRUSES • Highly tropic for epithelial cells of the skin and mucous membranes • Viral nucleic acid can be found in the basal stem cells • Late gene expression (capsid proteins) is restricted to the uppermost layer of differentiated keratinocytes • Stages in viral replicative cycles dependent on specific factors that are present in the sequential differentiated states of the epithelial cells (difficult to cultivate in vitro) .

BIOLOGIC CHARACTERISITICS • Species specific • Failure of terminal differentiation • Replication – terminally differentiated layer of the squamous epithelium • Viral DNA and RNA transcripts for early gene expression – basal layer .

SKIN WART (PAPILLOMA) Stratum corneum Stratum granulosum Capsid protein Virus particles Replicating virus particles Expression of early genes Viral DNA (low copy number) Stratum spinosum Basal cell (mitosis) .

PATHOGENESIS AND PATHOLOGY • Transmission: close contact • From the surface of the papillomatous lesion • Formation of warts at the cutaneous and mucosal sites • Skin warts. flat warts. laryngeal papillomas. penis and anus and a subset of head and neck cancers . plantar warts. anogenital warts. cancer of the cervix. vulva.

66. 39. 68. but some progress to malignancies 6. 4. 45. 11. 81 dysplasias and intraepithelial neoplasias (mucosal sites) 7 16. 58. 60. 59. Anogenital condylomas. 12. 40. 57 3. 35. 73. Low 61. 20. 70. 8. 47 Plantar warts Common skin warts Cutaneous lesions Epidermoplasia verruciformis Clinical Lesion Suspected Oncogenic Potential Benign Benign Low Mostly benign. 56. 10. 18. 9. 30. 76. 72. 31. 28. 17. 54. laryngeal and esophageal carcinomas Low High correlation with genital and oral cancer especially cervical cancer . 27. 42-44. 36. 51-53. 33. laryngeal papillomas. 78 5.Examples of Association of Human Papillomaviruses with Clinical Lesions Human Papillomavirus Type 1 2. 49. 82 Hand warts of butchers High-grade dysplasias and carcinomas of genital mucosa.

20. 56. Low 61.Examples of Association of Human Papillomaviruses with Clinical Lesions Human Papillomavirus type 1 2. 17. laryngeal and esophageal carcinomas Low High correlation with genital and oral cancer especially cervical cancer High cancer risk! . 42-44. 40. 39. 45. 30. 28. 10. 76. 31. 66. 9. 73. 60. 8. 68. 78 5. 57 3. 35. 18. Anogenital condylomas. 81 dysplasias and intraepithelial neoplasias (mucosal sites) 7 16. 51-53. 27. 47 Plantar warts Common skin warts Cutaneous lesions Epidermoplasia verruciformis Clinical Lesion Suspected Oncogenic Potential Benign Benign Low Mostly benign. 4. but some progress to malignancies 6. 11. 59. 36. 70. 12. 49. 82 Hand warts of butchers High-grade dysplasias and carcinomas of genital mucosa. 33. laryngeal papillomas. 72. 54. 58.

vagina and vulva .CONDITIONS CAUSED • • • • • Warts (common. plantar or flat) Epidermodysplasia verruciformis Condyloma acuminata (Genital warts) Laryngeal papillomas Human Papillomas in cancer – Squamous cell carcinoma – Premalignant and malignant lesions of the uterine cervix.

Epidemiology and Clinical Associations • Warts (common. plantar or flat) – Children and young adults – Contact and minor abrasions – No specific predisposing factors – Extensive disease – primary immunodeficiencies. on immunosuppressive therapy .

But for excessive warty disease. plantar or flat) HPV types 1 through 3 5 to 15 years old HPV-4 HPV-7 20 to 25 years old meat handlers MODE OF TRANSMISSION : direct contact or wound abrasion No specific predisposition. Spontaneous regression . may be associated with primary immunodeficiencies.Epidemiology and Clinical Associations • Warts (common.

9.Epidemiology and Clinical Associations • Epidermodysplasia verruciformis – Warts and macular lesions – Familial. 17. autosomal recessive – Depressed cell-mediated immunity – Lifetime persistence of disseminated wart lesions – HPV serotypes 5. and 19 to 25 – Natural route of transmission – not known . 12. 14. 8. 15.

Epidemiology and Clinical Associations • Epidermodysplasia verruciformis – Malignant transformation • 25% • HPV-5 • Sun-exposed areas .

. in pregnancy) • Regress • Recurrence – extensive lesions • Malignant transformation – vulva.Epidemiology and Clinical Associations • Condyloma acuminata (Genital warts) – Young adults • HPV types 6 or 11 • Venereal transmission • Predisposing factors – Sexual promiscuity – Hormonal imbalance (e. penis and anus .g.

unprotected intercourse – Children • Sexual abuse • Perinatal transmission .Epidemiology and Clinical Associations • Condyloma acuminata (Genital warts) – Older adults • 75% .

Epidemiology and Clinical Associations • Condyloma acuminata (genital warts) – High incidence of HPV DNA in persons with no clinically diagnosable HPV-associated disease – Subclinical – Cofactors – trauma of sexual activity and smoking .

Epidemiology and Clinical Associations • Recurrent Respiratory Papillomas (Laryngeal Papillomas) – Juvenile type • Children younger than 5 years of age • HPV types 6 or 11 • Perinatal transmission – Adults • Frequent and rapid recurrence • Malignant conversion – rare – radiation or heavy smoking .

Epidemiology and Clinical Associations • Epidermal Infections are associated with: – Antibodies • Serotype-specific • IgM and IgG – Cell-mediated immunity Correlated with resolution of warts .

PATHOGENESIS AND PATHOLOGY • Behavior of HPV lesions is influenced by immunologic factors • CMI • Nearly all HPV infections are cleared and become undetectable in 2 to 3 years • Cervical cancer – persistent with high risk HPV is a necessary component to progression to malignancy .

CLINICAL FINDINGS AND EPIDEMIOLOGY • An estimated 660 million have HPV infection. the most common viral infection of the reproductive tract. • Peak incidence occurs in adolescents and young adults .2 million new cases reported annually in the U. • An estimated 6.S.

• HPV – accepted as the cause of anogenital cancers. • 99% of cervical cancer patients and over 80% of anal cancers are linked to genital infections with papillomaviruses • HPV 16 and 18 – found most frequently in cervical cancers. responsible for 70% of all cervical cancers (HPV 16 being the most common) .

• Anal cancer .associated with high-risk HPV infection • At risk: – Immunocompromised individuals – Men who have sex with men – Oropharyngeal cancers (subtype of head and neck squamous cell carcinomas) – Linked to HPV 16 .

• Anogenital warts • HPV 6 and 11 • Laryngeal papillomas in children (recurrent respiratory papillomatosis) • HPV 6 and 11 • Passage through the birth canal • Causes obstruction (asphyxiation) • Benign Genital Condylomas • HPV 6 and 11 .

• Normal Skin – high prevalence of HPV DNA in healthy adults • Immunosuppressed individuals have an increased incidence of warts and cancer of the cervix • All HPV cancers occur more frequently in persons with HIV/ AIDS .

Human Papillomaviruses in Cancer • Squamous cell carcinoma – HPV-6 • Juvenile laryngeal papillomatosis • Condyloma acuminata – HPV-5. less commonly HPV-8 and HPV-14 • Epidermodysplasia verruciformis .

33 and 35 – Smoking . vagina and vulva – HPV-16 • most common • 25% .CIN III • 33% to 70% .Cervical Neoplasia • Premalignant and malignant lesions of the uterine cervix.invasive cervical CA – Others – HPV-18.

Treatment • Removal of the lesion – Podophyllin – Cryosurgery – common warts – Laser therapy – refractory genital or respiratory lesions .

Treatment • Immunomodulation – Alpha-interferon • Systemic and intralesional • Extensive refractory genital and respiratory papillomatosis • Specific – Topical idoxuridine • Extensive genital warts – Systemic cytotoxic chemotherapy .

Treatment • Hypnosis and suggestion – Hand warts – Highly effective .

16 and 18) • Bivalent vaccine (HPV 16 and 18) • Not effective against established HPV disease • Target: adolescent and young adult females • Immunity – maybe up to 5 years • Not recommended for pregnant women .PREVENTION AND CONTROL • AGAINST CERVICAL CANCER • Quadrivalent vaccine (HPV 6. 11.

POLYOMAVIRIDAE .

45nm in diameter DNA (10%). circular.POLYOMAVIRIDAE • • • • • Virion: Composition: Genome: Proteins: Envelope: – – – – – Icosahedral. Protein (90%) dsDNA. 8kbp 3 structural proteins. cellular histones condense DNA in virion none • Outstanding characteristics: Stimulate cell DNA synthesis Viral oncoproteins interact with cellular tumor suppressor proteins Important model tumor viruses Human viruses can cause human neurologic and renal disease May cause human cancer .

DNA-containing tumor viruses • • • • • • SV40 from monkeys and humans BK virus JC virus KI virus Merkel cell virus from humans Murine polyoma virus .

POLYOMAVIRUS REPLICATION • GENOME contains • “Early” regions • “Late” regions .

POLYOMAVIRUS REPLICATION • “EARLY” REGIONS • Expressed soon after infection of cells • “LATE” REGIONS • Codes for the synthesis of coat proteins • Transforming proteins must be continually synthesized for cells to stay transformed • No role in transformation • Not expressed in transformed cells .

BK AND JC VIRUSES • Widely distributed in human populations • Antibodies present in 70-80% of adult sera • Infection occurs in childhood • Persists in kidneys and lymphoid tissues of healthy individuals after primary infection • May reactivate when host immune response is impaired .

BK AND JC VIRUSES • Viral reactivation and shedding of virus in urine are asymptomatic in immunocompetent persons • Commonly isolated from immunocompromised patients .

BK AND JC VIRUSES • BK VIRUS • Causes: – hemorrhagic cystitis in bone marrow transplant recipients – Polyoma-virus associated virus nephropathy in renal transplant patients • JC VIRUS • Associated with human brain tumors but an etiologic role is not yet established • Causes: – progressive multifocal leukoencephalopathy – (fatal in patients with depressed CMI due to immunosuppressive therapies or infection with HIV) .

Oncogenicity • No data exist linking JCV or BKV to human carcinomas .

others – SV40-like virus • Gray and white matter • Diffuse throughout the neuroaxis • Small. discrete areas of demyelination  confluence .Progressive Multifocal Leukoencephalopathy (PML) • Oligodendrocytes • JCV – most common.

.

Progressive Multifocal Leukoencephalopathy (PML) • Diagnosis – Brain biopsy – Serology • Not helpful • High prevalence of antibody in the general population • Impaired immune responses .

Progressive Multifocal Leukoencephalopathy (PML) • Treatment – None • Prophylaxis – Alpha-interferon in renal transplant patients .

MERKEL CELL POLYOMAVIRUS • KI AND WU VIRUSES • Discovered in 2007 in nasopharyngeal aspirates from children with respiratory infections • MERKEL CELL POLYOMAVIRUS • 2008 • Identified in Merkel cell carcinomas (rare skin tumors of neuroendocrine origin) .KI AND WU VIRUS.

SV40 • Replicates in certain types of monkey and human cells • Highly tumorigenic in experimental inoculated animals • May be transmitted via fecal-oral route in humans .

Transmission electron micrograph of Polyoma virus SV40 .

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