Information presented to studends as part of Capstone project

1. The Human Papillomavirus: Colleen R. Barrett, MSN, FNP-BC Doctor of Nursing Practice Student, Robert Morris University

2. The Human Papillomavirus HPV is the most common STI in the United States (Fontenot, et al., 2007) 6.2 Million US residents contract HPV annually >50% of sexually active men and women will acquire the infection at some point in their lives. (CDC, 2007)

3. The Human Papillomavirus Worldwide, HPV infection is the most common viral infection of the anogenital tract Lifetime risk of acquiring infection is as high as 70% (Block ,et al., 2006)

4. The Human Papillomavirus A DNA tumor virus Can infect almost all human skin surfaces all types of squamous epithelium Can cause Cancer in most sites it infects

5. The Human Papillomavirus Sexually transmitted Sexual intercourse not required for transmission Can be transmitted through intimate contact

6. The Human Papillomavirus Virus can be asymptomatic Prevalence highest among women younger than 25 Second peak in incidence after age 55 Incidence distributed equally throughout society Widely spread even in relatively low risk populations

7. Pathogenesis Incubation period usually 3 to 4 months Range is from 1 month to 2 years Can clear spontaneously or can progress to pre-cancerous or cancerous cervical abnormalities

8. Risk Factors for HPV Sexual behavior Frequency of sexual intercourse Early onset of sexual activity Number of lifetime sexual partners Male partner’s number of lifetime partners Age Ethnicity Smoking or living with smokers OC use, pregnancy, and immunosuppression are also factors (Buttin, Herzog, and Mutch, 2006)

9. Types of HPV High Risk HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 55, 56, 58, 59, 66, 68 (oncogenic types) Low risk HPV types 6, 11, 26, 42, 44, 54, 70, 73 (non-oncogenic) (Buttin, Herzog, and Mutch, 2006)

10. Types of HPV HPV 1 causes plantar warts (verrucaplantaris) HPV 6 and 11 cause anogenital warts (condylomaacuminatum) HPV 16 and 18 cause cervical cancer

11. HPV Related Illness Anogenital warts Cervical dysplasias Cervical cancer Squamous cell carcinomas and dysplasias of the penis, anus, vagina, and vulva DNA of HPV has been detected in tissue of oral and tonsillar cancers(Vokes, 2008)

12. Oral HPV

13. HPV Related Illness Of all STI’s, HPV and Hepatitis B are the largest causes of cervical and hepatocellularcarcinomasrespectively The two most common malignancies in the developing world (Holmes, 2008)

14. Anogenital Warts One of the most common sexually transmitted diseases in the United States Individuals without obvious disease may transmit infection

15. Penile and Vulvar HPV (Genital Warts)

16. HPV and Cervical Dysplasia HPV infection is associated with a 4-fold increased risk of developing pre-cancerous cervical abnormalities (Glass) 48% of women will develop evidence of HPV infection within 3 years of initiation of sexual activity (Schmiedeskamp, et al., 2006)

17. HPV and Cervical Dysplasia Most HPV infections clear spontaneously Persistent infection will usually lead to cervical abnormalities within 24 months

18. HPV and Cervical Dysplasia Atypical Squamous Cells of Undetermined Significance (ASCUS) Low Grade Squamous Intraepithelial Lesions (LSIL) Cervical intraepithelial neoplasia I (CIN I) High Grade Squamous Intraepithelial Lesions (HSIL) CIN II and III, Carcinoma in situ

19. HPV and Cervical Cancer U.S. in 2006 U.S. in 2007 9,700 new diagnoses 3,700 cases resulted in death (American Cancer Society, 2006) 11,150 new diagnoses 3,670 cases resulted in death (Holmes, 2008)

20. HPV and Cervical Cancer HPV is associated with 99.7% of all cervical cancers worldwide Once HPV has been contracted, relative risk for development of cervical cancer is 20 to 70% Only about 1% of women infected with oncogenic HPV will go on to develop cervical cancer. (Buttin, Herzog, Mutch, 2006)

21. HPV and Cervical Cancer Worldwide: 370,000 cases of cervical cancer diagnosed annually 270,000 cases will result in death (Block, et al., 2006) Number one cause of cancer death among women in developing countries

22. HPV and Cervical Cancer Cervical cancer screening programs in developed countries have reduced the incidence of invasive cervical cancer by approx. 80% 20 to 25% of women considered to be high risk are still missed by screening programs (Adams, Jasani, Fiander, 2007)

23. Progression of Cervical Disease

24. Normal Cervix and Cervical Cancer

25. Lack of Awareness of HPV Numerous surveys on college campuses in US and Canada Students unaware of the existence of HPV Unaware of link between HPV and cervical cancer

26. HPV Vaccine Gardasil earned FDA approval June 2006 Quadrivalent vaccine (Gardasil) contains protection from HPV 6, 11, 16, and 18 Bi-valent vaccine will soon be available; provides protection from HPV 16 and 18 only.

27. Gardasil Vaccine Approved for females ages 9 to 26 years of age Three series vaccine given at 0, 2 and 6 months

28. Gardasil Vaccine Two major clinical trials ongoing Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE) Both studies designed, managed and analyzed by Merck (company that manufactures and sells the vaccine). Both are double blind, randomized, placebo controlled trials.

29. Gardasil Study Designs FUTURE I GRoup FUTURE II Group 5,455 subjects 16-24 years of age 62 study sites, 16 countries Subjects drawn from communities near universities. Subjects followed for 3 years after 1st dose. 12,167 subjects 15 to 26 years of age 90 study sites, 13 countries Looked at HPV types 16 and 18 only Followed for 3 years after 1st dose

30. Study Results FUTURE I: Per protocol population Vaccine 100% effective in preventing vaginal, vulvar, perineal, perianal intraepithelial lesions or warts associated with vaccine type HPV 100% effective in preventing CIN grades 1 to 3 or adenocarcinoma in situ (AIS) associated with vaccine type HPV (Future I study group, 2007)

31. Study Results FUTURE I: Efficacy also found in the unrestricted population Efficacy of vaccine against vaccine type HPV found to be 95% for all grades of external anogenital or vaginal lesions

32. Study Results FUTURE I Unrestricted population Efficacy of vaccine against vaccine type HPV found to be 98% for all grades of cervical lesions. HPV disease incidence in the vaccine group did not continue to grow.

33. Study Results FUTURE I: Analysis regardless of HPV status at entry to study Vaccine efficacy 73% for all grades of vaccine type HPV anogenital and vaginal lesions combined Vaccine efficacy 55% for all vaccine-type HPV induced cervical lesions combined

34. Study Results FUTURE II: Per protocol population: vaccine efficacy 98% for prevention of HPV 16/18 related high grade cervical lesions Unrestricted population: vaccine efficacy 95% for prevention of HPV 16/18 related high grade cervical lesions (Future II Study Group, 2007)

35. Study Results FUTURE II: Analysis regardless of HPV status at entry to study Vaccine efficacy 44% for High grade HPV 16/18 related cervical disease Cervical abnormalities related to HPV 16/18 did not continue to grow in the vaccine group

36. Gardasil Vaccine Vaccination is prophyllactic (preventative) Vaccine will not alter the course of disease or infection present prior to being vaccinated. No waning of immunity was found after 5 years of follow up

37. Gardasil Vaccine Side Effects: Injection site irritation (redness, itching, swelling, pain) Fever Syncope has been noted anecdotally

38. Post Market Analysis Most commonly reported adverse events Dizziness Syncope Injection site pain nausea

39. Post Market Analysis Monitoring for and investigating reports of: GuillaineBarre Syndrome Seizure Syncope Anaphylaxis Appendicitis Stroke Thrombus Pulmonary Embolus

40. References Adams, M., Jasani B., & Fiander, A. (2007). Human papillomavirus (HPV) prophylactic vaccination: Challenges for public health and implications for screening. Vaccine, 25, 3007-3013. American Cancer Society. Cancer Facts and Figures. Atlanta, Ga.: American Cancer Society, 2006. Block, S., Nolan, T., Sattler, C., Barr, E., Giacoletti, K. E. D., Marchant, C. D. et al. (2006). Comparison of the immunogenicity and reactogenicity of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, 18) l1 virus-like particle vaccine in male and female adolescents and young adult women. Pediatrics, 118(5), 2135-2145.

41. References Buttin, B. M., Herzog, T. J., and Mutch, D. G. (2006). Abnormal cytology and human papillomavirus. In M. Curtis, S. Overholt, & M. Hoplkins (Eds.), Glass’ Office Gynecology (pp 80-106). Lippincott Willimas & Wilkins. Center for Disease Control and Prevention. Human papillomavirus: HPV information for clinicians. Available at: www.cdc.gov/std/hpv. Fontenot, H. B., Collins Fantasia, H., & Allen, J., D. (2007, October 1). HPV in adolescents: Making the wake up call. Advance for Nurse Practitioners, 15(10), 73-76.

42. References Future I Study Investigators. (2007). Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. The New England Journal of Medicine, 356(19), 1928-1943. Future II study group. (2007, May 1). Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. The New England Journal of Medicine, 356(19), 1915-1927. Holmes, K. K. (1992). Sexually transmitted infections: overview and clinical approach. In A. S. Faiuci, et al. (Eds.), Harrison’s Principles of Internal Medicine, 17th edition (pp 548-551). The McGraw Hill Companies, Inc

43. References Schmiedeskamp, M. R., Kockler, D. R. Human papillomavirus vaccines. Annals of Pharmacotherapy, 2006; 40(7-8): 1344-1352. Vokes, E. (2008). Head and neck cancer. In A. S. Faiuci, et al. (Eds.), Harrison’s Principles of Internal Medicine, 17th edition (pp 548-551). The McGraw Hill Companies, Inc.

44. Questions and Answers….