Human Papillomavirus (HPV)

2. Human Papillomavirus (HPV) Genital Warts F.Iraji MD

3. A human papillomavirus (HPV) is a virus that infects the epidermis and mucous membranes. • Over 130 HPV Types • Lifecycle somewhat unknown. • Several months to years may elapse before the abnormal growth of cells

5. Human Papillomavirus(commonly called Genital Warts) • Human Papillomavirus (HPV) is a virus that can cause various disease states including “genital” or “venereal” warts • Papillomaviruses are a complex group of DNA tumor viruses. They can cause benign growths (papillomas), cancers, or more commonly, transient infections • HPV infection is causally associated with cervical cancer ; other genital cancers including anal, penile, vulvar, and vaginal cancers may have HPV as co-factor

8. Human Papillomavirus Cervical Cancer

9. HPV Prevalence • Most common STD • Yearly incidence of 6.2 million • 20 million currently infected • 80 million infected at least once between the ages of 15-49 • An estimated 9.2 million sexually active adolescents and young adults 15-24 years of age are infected with genital HPV • An estimated 5%-30% of people infected with genital HPV are infected with multiple types of the virus • 316,000 initial visits to physicians’ offices (2004)-genital wart diagnosis

10. GENITAL HPV INFECTION1% 1.4 MILLION VISIBLE WARTS4% 5 MILLION Subclinical (Colposcopy)10% 14 MILLION Subclinical (DNA testing)60% 81 MILLION Prior infection (+ antibodies)25% 34 MILLION No prior/current infection

11. Epidemiology of HPV and Cervical Cancer • Over 99% of cervical cancers have HPV DNA detected within the tumor • 70% of cervical cancer is caused by one of two types of HPV, 16 or 18 • The quadrivalent HPV vaccine protects against Types 6, 11, 16 and 18

12. HPV • Small virus – 130 types • Low-risk e.g. 6, 11 • High-risk e.g. 16, 18 • Associated with various disease from skin warts to cervical cancer • Transmission via skin-to-skin/sexual • Most common STD

13. Pathogenesis HPV Genotyping System Genital HPV types are generally characterized in terms of oncogenic potential. • Low-risk types (nononcogenic types) • Most genital warts caused by HPV types 6 and 11 • Recurrent respiratory papillomatosis associated with HPV types 6 and 11 • High-risk types (oncogenic types) • HPV types 16 and 18 found in 70% of cervical cancers • Most women with high-risk HPV infection have normal Pap test results and never develop cellular changes or cervical cancer.

14. Pathogenesis Pathology • HPV infects the basal cell layer of stratified squamous epithelium and stimulates cellular proliferation. • Affected cells display a broad spectrum of changes, ranging from benign hyperplasia, to dysplasia, to invasive carcinoma.

15. Pathogenesis Natural History of HPV • Most genital HPV infections are transient, asymptomatic (subclinical), and have no clinical consequences in immunocompetent individuals. • Time to development of clinical manifestations is variable. • Median duration of new cervical infections is 8 months, but varies. • 90% of infections clear within 2 years • Gradual development of an effective immune response is the likely mechanism for HPV DNA clearance.

16. Pathogenesis Natural History of HPV-continued • Persistent HPV infection • Not cleared by the immune system • Characterized by persistently detectable type-specific HPV DNA • Persistent oncogenic HPV infection is most important risk factor for precancerous cervical cellular changes and cervical cancer.

17. How does HPV cause cancer? HPV infection Persistent HR HPV infection Normal epithelium CIN Invasive carcinoma 10-20+ years HPV clearanceNo lesion> 80% HPV clearance & regression dependent on age, degree of CIN lesion & immune status

18. Strength of Association Relative Risk Carcinogenic Agent > 500 High Risk HPV and cervical cancer - Philippines, Costa Rica, Bangkok 50-100 Hepatitis B virus and liver cancer - Taiwan, Greece 20 Hepatitis C virus and liver cancer - Italy, Spain 10 Cigarette smoking and lung cancer

19. HR HPV

20. 2 opportunities to prevent cervical cancer Cervical screening & treatment Prophylactic HPV vaccination

21. Questions?

22. Epidemiology of HPV and Cervical Cancer • Over 99% of cervical cancers have HPV DNA detected within the tumor • 70% of cervical cancer is caused by one of two types of HPV, 16 or 18 • The quadrivalent HPV vaccine protects against Types 6, 11, 16 and 18

23. Risk Factors for Acquiring a Genital HPV Infection • Young age (less than 25 years) • Multiple sex partners • Early age at first intercourse (16 years or younger) • Male partner has (or has had) multiple sex partners

24. HPV Transmission • Direct skin-to-skin contact • Usually, but not always sexual contact • Infected birth canal • Fomites (very rare) Friction and abrasion are key factors. Difficult to determine how and where infection occurred due to poor standardized tests and variable latency periods.

25. How is HPV spread? Any kind of sexual activity involving skin to skin genital contact with an infected person — intercourse isn't necessary. People with HPV may not show any signs or symptoms, so they can pass the virus on without knowing it.

26. What about oral sex? • It can occur in the mouth, throat or respiratory tract • It is relatively uncommon • It appears to be an inefficient mode for transmission

27. HPV Incubation • Average incubation is 3 weeks to 1 year • Possibly years before appearance of warts or cervical abnormalities • Some will be transient and may never be detected

28. Common Symptoms of Genital Warts in Males & Females • The symptoms may include single or multiple fleshy growths around the penis, scrotum, groin, vulva, vagina, anus, and/or urethra • They may also include: itching, bleeding, or burning, and pain • The symptoms may recur from time to time

29. Clinical Manifestations Genital Warts-Duration and Transmission • May regress spontaneously, or persist with or without proliferation. • Frequency of spontaneous regression is unclear, but estimated at 10–30% within three months. • Persistence of infection occurs, but frequency and duration are unknown. • Recurrences after treatment are common.

30. Clinical Manifestations Genital Warts and High-Risk HPV • High-risk HPV types occasionally can be found in visible warts and have been associated with squamous intrepithelial lesions (squamous cell carcinoma in situ, Bowenoidpapulosis, Erythroplasia of Queyrat, or Bowen’ s disease of the genitalia). • The lesions can resemble genital warts. • Unusual appearing genital warts should be biopsied.

31. Genital Warts in a Male Source: CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides Source: Cincinnati STD/HIV Prevention Training Center

32. HPV Penile Warts Source: Cincinnati STD/HIV Prevention Training Center

34. Pearly Penile Papules

35. Vestibular papillomatosis

36. Intra-meatal Wart of the Penis(and Gonorrhea) Source: Florida STD/HIV Prevention Training Center

37. Circumcision and HPV • Risk for penile cancer • May influence the risk of HPV acquisition, transmission and cervical cancer

38. Female Genital Warts Source: CDC/NCHSTP/Division of STD, STD Clinical Slides

39. Clinical Manifestations Perianal Warts Source: Seattle STD/HIV Prevention Training Center at the University of Washington/ UW HSCER Slide Bank

40. Clinical Manifestations Vulvar Warts Source: Reprinted with permission of Gordon D. Davis, MD.

43. HPV Warts on the Thigh Source: Cincinnati STD/HIV Prevention Training Center

44. Perianal Warts Source: Cincinnati STD/HIV Prevention Training Center

45. Complications of Genital Warts(if untreated) • It may destroy body tissue around the genitals and anus • For pregnant women • Delivery complications or need for C-section • Juvenile Onset Recurrent Respiratory Papillomatosis (JO-RRP)

46. Testing & Treatment for Genital Warts • Can be detected in a clinical exam; • Can be treated by removing the warts; • The virus cannot be removed, so the warts may grow back.

47. Clinical Manifestations Cervical Cellular Abnormalities • Usually subclinical • Lesions associated with these abnormalities can be detected by Pap test or colposcopy, with or without biopsy. • Can be caused by HPV • Low-grade lesions often regress spontaneously without treatment.

48. Clinical Manifestations Classification of Cervical Cellular Abnormalities 2001 Bethesda System • Atypical Squamous Cells (ASC-US and ASC-H) are cells that do not appear to be completely normal • Atypical Squamous Cells of Undetermined Significance (ASC–US) • Changes are often caused by HPV infection. • Changes are usually mild. • Atypical Squamous Cells cannot exclude a High-Grade Squamous Intraepithelial Lesion (ASC–H). • Changes are more likely to be associated with precancerous abnormalities than ASC-US.

49. Clinical Manifestations Classification of Cervical Cellular Abnormalities-continued • Low-grade squamous intraepithelial lesion (LSIL) • Usually transient, caused by HPV infection • High-grade squamous intraepithelial lesion (HSIL) • Generally changes due to persistent infection with a high-risk HPV type • Lesions associated with HSIL have a higher risk for progression to cervical cancer.

50. HPV Diagnostic Techniques • History • Visual exam • Pap smears • DNA testing