10 Papillomaviruses

8/16/2019 10 Papillomaviruses

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Purnomo HadiMikrobiologi FK UNDIP


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nonenveloped55 nm in diameter icosahedral capsid composed of 72

capsomeres:• two capsid proteins. major capsid protein (80%). 56,000 Da

minor capsid protein, 76,000 Da

double-stranded, circular DNA genome> 70 tipe


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Prevalence• 630 million currently infected

Geographic variations• Prevalence of HPV in sub-Saharan Africa 3 times

US


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5/25

Over 80 non-cancer causing subtypes• Types 6 and 11 are responsible for causing over

90% of all anogenital warts

No available antiviral treatment for anyHPV subtypes


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Manifestasi Klinik Wart Tipe Papilloma virus

Condyloma acuminate 6, 11, 16

Carcinoma cervix 16, 18Laryngeal 6, 11, 30

Plantar 1, 4

Tangan 2

Epidermodysplasia

verruciformis(autosomal recessive)

5, 8

Butcher’s warts (jagal) 7

Ca-Cervix: 7% negara maju, 24% negara berkembang


7/25

Close personal contact: cutaneous warts,

minor trauma?

Sexually: anogenital warts• Recurrent respiratory papillomatosis in young

children is thought to be acquired by passage

through an infected birth canal.


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Skin-skin contact

• Genital-genital

• Manual-genital

• Oral-genital Does not require penile vaginal sexual

intercourse

Condoms of uncertain effectiveness

• As opposed to discharge diseases like HIV,gonorrhea, syphilis


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Mikrolesi, masuk dalam sel basal epitelsquamus

infected epithelium characteristically:• enlarged, hyperchromatic nuclei,• with or without cytoplasmic halos (koilocytotic

atypia), and

• mature virus concentrates

Site Specificity:• squamous epithelium• squamo-columnar junctions


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Manifestasi Klinik


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Prevalence

• 1% of sexually active adults

Treatment

• 40% or more resolve spontaneously• Recurrence is fairly common

• Various agents including Aldara, cryosurgery

(freezing), podophylin, cautery

NO ASSOCIATION WITH CANCER


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Normal

Cervix

HPV

Infection

Persistent

HPV

Infection

Cervical

Dysplasia

(pre-cancer)

Cervical Cancer


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Cervical intraepithelial neoplasia (CIN)1

• CIN 1: Mild dysplasia; includes condyloma (anogenital

warts)

• CIN 2: Moderate dysplasia

• CIN 3: Severe dysplasia; includes CIS

1. Bonnez W. In: Richman DD, Whitley RJ, Hayden FJ, eds. Washington, DC: American Society for Microbiology Press;2002:569 –612. 2. Ostor AG. Int J Gynecol Pathol . 1993;12:186 –192.

CIN caused by HPV can clear without treatment.2

CIN1 Normal

CIN 1(condylom

a)

CIN 1(mild

dysplasia)

CIN 2(moderate

dysplasia)

CIN 3

(severe dysplasia/CIS)

Invasive

Cancer

Histology of

squamous

cervical

epithelium1

Basal cellBasal membrane


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Risk factors forpersistent HPVinfection• Lifetime number of

sexual partners

• Age at first intercourse

• Smoking

• Oral contraceptive use

• Male partner sexualbehavior

Additional risk

factors

• Age

• Genetics• Low socioeconomic

class

• Nutrition

• Immune suppression


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HPV Infection

Low-grade

Dysplasia

High-grade

Dysplasia

Cervical

Cancer

10,000,000

1,000,000

300,000

12-14,000 - 4,000 deaths/year

9th most common female cancer


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HPV Infection

Low-grade

Dysplasia

High-grade

Dysplasia

Cervical

Cancer

300,000,000

30,000,000

10,000,000

2,300,000 - 288,000 deaths/year

2nd leading cause of cancer deaths among

women


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PAP Smear• Detects precancerous cells

• Should begin by age 21 or within 3 years of

onset of first sexual intercourse

If abnormal• HPV DNA testing

•

Colposcopy and Biopsy


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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

Condoms?

•

Transmitted through skin-skin contact and can occurin male and female genital areas not covered


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Merck (first of 2) - likely to market in 2007• Subtypes 16, 18, 6, 11 ~70% of high risk types for cervical cancer

~90% of types for anogenital warts

• Lifetime effectiveness? - 3 years• Who? 13-14 year old girls

Others at risk


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Change screening guidelines in US?

Clearly may be most effective in

developing world where cervical cancer

prevalence is high and screening for

cervical cancer is not widely available

3 injections

Cost?


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ClinicallyTCA: Application for 3 to 5 minutes of a

3% to 5% acetic acid solution aceto-

whiteningPap smear: histo-patologiPeroxidase-antiperoxidase

immunocytochemical stainingDetection and typing of HPV DNA:

• probe

• polymerase chain reaction


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CryotherapyElectrosurgical excisionTCA 50%Podophyllin, a cytotoxic agent that arrests

mitosis in metaphase, in combination with vidarabine, a DNA polymerase inhibitor.Cidofovir (acyclic nucleoside phosphonate

derivative), broad-spectrum activity against

DNA viruses IFNs intravaginal 5-fluorouracil


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Kondom + spermicide

Vaccination

Documents

10 Papillomaviruses