1. Papilloma Virus By Elizabeth Miltner, Shelton Chow, Paul Hoang and Alfredo Paredes

2. Pathogenesis Double stranded DNA virus Over 70 genotypes of HPV Human reservoir and worldwide occurrence Transmission via direct contact Infects epithelial cells –Junction of squamous and columnar epithelium Integrates into host genome in malignant lesions Contain “transforming genes” that play role in malignant transformation. Associated with cancer of the cervix and anal neoplasia

3. Clinical Presentation Mucosal Lesions:  Appear as single or multiple areas of thickened epithelium  May have fine hairlike surface projections  May be flat and diffuse or raised and pedunculated  Whitish mainly but may be reddish or pinkish color just like normal oral mucosa  May be found on soft and hard palate, lips, gingiva, buccal and labial mucosa, or floor of mouth depending on type of HPV

4. Skin Lesions:  Lesions are similar in appearance to oral lesions except that it is grayish brown in color due to the dry environment  Common on genitals, hands and fingers

5. Genital Lesions:  Soft, moist, or flesh colored  Can occur in clusters (cauliflower like bumps)  Can be raised or flat, small or large  Dry, painless, firm and rough in texture  In men  Can occur on scrotum or penis, on the anus and within the rectum  Can involve the urethra and bladder  In women:  Can occur on the vulva, cervix, vagina, and anus

6. Diagnostic Tests Can generally be diagnosed simply by their location and appearance. Verruca Vulgaris (warts): –Lesions are exophytic, keratinized, sessile papules or nodules with cauliflower surfaces. –Lesions usually measure 2 to 5 mm. –Biopsy to confirm diagnosis. Koilocytes indicate HPV infection.

7. Diagnostic Tests Condylomata acuminata (genital warts): –Present as solitary or multiple, pinkish, sessile papules or plaques with pebbled surfaces or as pedunculated papillary lesions. –In women, a pelvic examination may reveal growths on the vaginal walls or the cervix. –Colposcopy may be used to see lesions invisible to the naked eye. –The tissue of the vagina and cervix may be treated with acetic acid to make the warts visible. –A pap smear may note changes associated with HPV. If results indicate abnormal changes that may be due to a high-risk type of HPV, then DNA HPV testing may be ordered as a follow-up test.

8. Diagnostic Tests There are more than 100 types of HPVs. The HC2 High-Risk HPV DNA Test, manufactured by Digene Corp., can identify 13 of the high-risk types associated with the development of cervical cancer. The HPV DNA test does not test for cancer, but for the HPV viruses that can cause cell changes in the cervix. If left untreated, these changes can eventually lead to cancer in some women.

9. Histological Appearance of HPV

10. HPV infection characterized by cells with pyknotic, irregular nuclei and clear cytoplasm. Moderate squamous dysplasia is also present. Normal tissue from the cervix HPV lesions exhibit extensive epithelial hyperplasia with acantosis, fusion and blunting of rete pegs Human Papilloma Virus in Cervix

11. HPVs are small, double-stranded DNA viruses, which infect stratified squamous or endocervical glandular epithelium, where they stimulate epithelial proliferation with unusual arrangement of nuclear material (mitosoid cells). Microscopy view of normal cell on a Pap test. Koilocytes (LSIL,600x) A high-grade Squamous Intraepithelial Lesion (HSIL)

12. Treatment for HPV

13. Treatment Goals: relieve symptoms and clearance of visible warts Drug and/or Non-drug therapy Recurrence with both modalities is not uncommon

14. Drug Therapy Anogenital warts: –Patient applied: Podophyllotoxin, imiquimod –Provider applied: podopyllin, 80-90% TCA Cutaneous Warts – salicylic acid

15. Non-Drug Therapy Provide immediate removal of wart Safe during pregnancy Side effects may include: pain, ulcers and blistering Surgical therapies: –Cryotherapy –Excsion –Electrosurgery –Laser surgery

16. HPV Vaccine Gardasil® approved in 2006 for use in women Protects against four HPV types (6,11,16, 18), These genotypes are responsible for 70% of cervical cancers and 90% of genital warts. Current recommendations –Should be administered before start of sexual activity –In sexually active women vaccine will be effective if no prior infection by the 4 genotypes –Recommended for ages 11-26 years (but can be used in girls as young as 9) Efficacy studies in men are underway

17. References ASCCP: http://www.asccp.org/edu/practice/cervix/histology.shtml# CDC 2006 STD Treatment Guidelines Control of Commnicable Diseases manual. 18 th Edition, 2004. HPV and HPV Vaccine – Information for Healthcare Providers. CDC. http://www.cdc.gov/std/hpv/STDFact-HPV-vaccine-hcp.htm Pathology and Laboratory Medicine: http://www.fahc.org/pathology/Education/hpv_powerpoints.html Sapp JP, Eversole LR, Wysocki GP: Contemporary Oral and Maxillofacial Pathology Sherris Medical Microbiology. 4 th Edition, 2004. ACP PIER: The Physcian’s Information and Education Resource 2007. University of Washington, Department of Pathology: http://www.pathology.washington.edu/clinical/HPV/

18. Questions What is the reservoir for papilloma viruses that infect humans? a: livestock b: dogs c: humans d: reptiles The HPV vaccine protects against: a: genital warts b: focal epithelial hyperplasia c: cervical cancer d: both A and C