- Human papillomavirus (HPV) is a small non-enveloped DNA virus that infects squamous epithelia and mucous membranes, producing different types of warts or papillomas. Over 70 types of HPV exist. - HPV replicates in basal epithelial cells and causes lesions depending on the virus type, such as common warts or genital warts. HPV types 16 and 18 can cause invasive cancers like cervical cancer. - HPV is transmitted through direct skin or mucosa contact and shows tissue specificity. Diagnosis involves pathology, cytology, or nucleic acid tests to identify the HPV type. Prevention includes vaccines and Pap smears, while treatment consists of surgery.

3. • Harald zur Hausen

4. • Shilpa Shetty
• Jade Goody

5. PapillomavirusesPapillomaviruses

6. Classification
• Widespread in nature, infecting
many vertebrates
• Highly species specific
• 100 + HPV types, classified on
basis of nucleic acid homology

7. HUMAN PAPILLOMA VIRUS
• Small, DNA virus
• Non enveloped
• Produce benign/malignant
tumor
• Species specific

8. Replication cycle of a papillomavirus. To establish a wart or papilloma, the virus must infect a basal epithelial cell. Our knowledge is limited
about the initial steps in the replication cycle such as attachment (1), uptake (2), endocytosis (3), and transport to the nucleus and uncoating of
the viral DNA (4). Early-region transcription (5), translation of the early proteins (6), and steady-state viral DNA replication (7) all occur in the
basal cell and in the infected suprabasal epithelial cell. Events in the viral life cycle leading to the production of virion particles occur in the
differentiated keratinocyte: vegetative viral DNA replication (8), transcription of the late region (9), production of the capsid proteins L1 and L2
(10), assembly of the virion particles (11), nuclear breakdown (12), and release of virus (13). (From Fields Virology, 4th ed, Knipe & Howley,
eds, Lippincott Williams & Wilkins, 2001, Fig. 65-6.)
Papillomavirus replication

9. • Infect squamous epithelia and mucous
membrane
• Produce different types of warts or
papillomata
• Over 70 different types of HPV
• Lesion - based on types of virus

10. • Verruca vulgaris (common wart):
hand and feet of children
by types 1,2,3,4
• Condyloma acuminatum (genital wart):
external genitalia
by types 6 & 11
transmitted by venereally
may turn to malignant
• HPV 16 & 18 can cause severe invasive
malignancies such as cervical cancer

11. Human papilloma virus infections
• Transmission
– Direct contact with broken skin or mucosa
• Skin warts
• Genital tract HPV
• Mucosal HPV
• Various HPV types show tissue
specificity

12. From Medical Microbiology, 5th
ed., Murray, Rosenthal & Pfaller, Mosby Inc., 2005, Fig. 52-3.
Papillomavirus pathogenesis

13. Cervical HPV infection
Natural history of cervical HPV infection. Approximate number of US cases of the different categories of infeciton. Most subclinical infections
and low-grade dysplasias regress spontaneously. Even high-grade dysplasia has some potential to regress spontaneously. Infection with
HPV-16 or HPV-18 represents a minority of the subclinical infections and low-grade dysplasias, whereas they represent most of the high grade
dysplasias and invasive cancers. (From Fields Vriology (2007) 5th edition, Knipe, DM & Howley, PM, eds, Wolters Kluwer/ Lippincott Williams
& Wilkins, Philadelphia Fig. 62.18.)

14. From Medical Microbiology, 5th
ed., Murray, Rosenthal & Pfaller, Mosby Inc., 2005, Fig. 52-4.
Papillomavirus disease

20. Progression from benign cervical condylomatous liesion to invasive carcinoma. Infection by oncogenic HPV types, especially HPV16, may directly
cause a benign condylomatous lesion, low-grade dysplasia, or sometimes even an early high-grade lesion. Carcinoma in situ rarely occurs until
several years after infection. It results from the combined effects of HPV genes, particularly those encoding E6 and E7, usually after integration of the
viral DNA into the host DNA and a series of genetic and epigenetic changes in cellular genes. HSIL, high-grade squamous intraepithelial lesion,
LSIL, low-grade squamous intraepithelial lesion; CIN, cervical intraepithelial neoplasia. (From Fields Vriology (2007) 5th edition, Knipe, DM & Howley,
PM, eds, Wolters Kluwer/ Lippincott Williams & Wilkins, Philadelphia Fig. 62.16.)
HPV and cervical dysplasia

21. HPV and head & neck cancers
• http://www.nature.com/news/hpv-sex-cancer-a

22. Lab diagnosis
1. Microscopy: by EM
2. Culture: Inoculation in mice
Inoculation in chick embryo CAM
Tissue culture
3. Serology: Detection of antibody by
ELISA

23. Diagnosis
• Pathology, cytology
• Immuno-histochemistry
• Nucleic acid
– Hybridization (Southern, in situ), PCR
– Identification of specific HPV type can
assist in evaluating prognosis and
treatment
– Integration state?

24. Prevention/Treatment
• Recombinant virus-like particle
vaccines
– Gardasil
• FDA approved; HPV 16, 18, 6, 11
– Cervarix
• FDA approval pending; HPV 16, 18
• Pap smear
• Surgery

25. Jade Goody