Human Papilloma Virus (HPV)

1. Human Papilloma Virus (HPV) By haaneelodhi #1206

2. Table of Contents Introduction Pathogenesis HPV Life Cycle Transmission Clinical futures Laboratory Diagnosis Medical Management Risk Factors Prevention HPV Vaccine Vaccination Schedule Contraindications and precautions of vaccinations Adverse Reactions

3. Introduction Human papilloma viruses are known as HPV Affect the skin and moist membranes (eg. Vuvla, cervix, vagina, anus, mouth and throat) Are more than 100 different types (or strains) of HPV Each type identified by a different number (16 and 18 cause 70% of cervical cancers) Is common, most people will have this at some point in their lives Majority has no symptoms and can go away on its own Can cause changes in lining (known as high risk of HPV)

4. Introduction Con’t Are known as Dysplasia Changes cells have increased risk of becoming cancerous Others can cause warts, hence why it may be called the wart virus ( specifically includes types 6 and 11) Most commonly around the genital area, can be present elsewhere Types of HPV that cause warts do no change cells which leads to cancer Are known as low risk HPV’s

7. Pathogenesis HPV infection occurs at basal epithelium Most infection resolve spontaneously Small portion will remain persistent and become an important risk factor for cervical cancer A common manifestation is CIN (Cervical intraepithelial neoplasia) Within a few years, Low grade CIN (CIN-1) may develop and can spontaneously resolve and the infection can be cleared

8. Pathogenesis Con’t Persistent HPV infection progress to high grade CIN (CIN-2, 3) Risk for progression to cancer If left untreated, Cervical cancer may arise with years or decades Infection with one type or HPV does not prevent infection with another type

10. Human papillomavirus Types and Disease Association

11. Replicative Stage Virus infects basal layer Enters cell, delivers DNA to cell nucleus First gene to be expressed are E6 and E7 E6 and E7 inhibit apoptosis E6 binds and inhibit P53 E6 also activates telomerase which allow cells to replicate E7 promotes cell division by binding to Rb E2f is unbound from Rb which cause DNA to replicate Infected basal cells divide

12. Replicative Stage Cont’ E1 and E2 are DNA binding protiens that regualte transcription and regulation of the viral genome E1 is a helicase E2 is a trancription factor E4 may be involved in activation the productive phase of the life cycle E5 is involved in transformation, enhancing the activity of epidermal growth factor

13. Repilicative stage Cont’ Cells approach terminal differentiation and late genes L1 and L2 are activated These encode major/minor capsid protiens Cells approach surface of the skin and continue to affect others

14. The Life Cycle

15. Transmission Skin-to-skin contact with the penis, scrotum, vagina, vulva, or anus Using a condom does not guarantee protection Genital warts are spread during oral, vaginal, or anal sex with infected partner (66%) whose have sexual contact with an infected partner will develop warts themselves within three months Can also be transferred from a woman to a newborn at the time of birth

16. Clinical Features Most HPV infections are asymptomatic and result in no clinicldesiease Manifesations include Anogenital warts Recurrent papillomatosis Cervical cancer precursors (CIN) Cancer (cervix, anal, vaginal, vulvular, penile, and some head and neck)

17. Clinical Findings Irregular, intermenstrual (between periods) or abnormal vaginal bleeding after sexual intercourse; Back, leg or pelvic pain Fatigue, weight loss, loss of appetite Vaginal discomfort or odorous discharge Single swollen leg

18. Cervix

19. Genital Warts-Appearance Condylomataacuminata Cauliflower-like appearance Skin-colored, pink, or hyper pigmented May be keratotic on skin; generally nonkeratinized on mucosal surfaces Smooth papules Usually dome-shaped and skin-colored Flat papules Macular to slightly raised Flesh-colored, with smooth surface More commonly found on internal structures (i.e., cervix), but also occur on external genitalia Keratotic warts Thick layer that can resemble common warts or seborrheickeratosis

21. Genital Warts-Symptoms Genital warts usually cause no symptoms Symptoms that can occur include: Vulvar warts-dyspareunia, pruritis, burning discomfort; Penile warts-occasional itching Urethral meatal warts-hematuria or impairment of urinary stream Vaginal warts-discharge/bleeding, obstruction of birth canal (secondary to increased wart growth during pregnancy) Perianal and intra-anal warts-pain, bleeding on defecation, itching Most patients have fewer than ten genital warts, with total wart area of 0.5–1.0 cm2.

22. Natural History of HPV Infection

24. Laboratory Diagnosis Infection is identifies by detection of HPV DNA from samples Vinegar (acetic acid) solution test: Solution will turn HPV infected areas white Pap Test: Collecting a sample of cells from the cervix to reveal any abnormality DNA Test: Recognize the DNA of HPV and can link to genital cancer, sample taken from cervix

25. Medical Management No specific treatment Treatment depends on symptoms of infection (such as genital warts or abnormal cervical cell cytology Genital warts can go away on there own. If not, they can be treated with medications such as Podofiloxor removed by surgery

26. Risk Factors Most studies suggest that young age (less than 25 years) is a risk factor Others include number or pregnancies, genetic factors, inconsistent condom use, smoking, and oral contraceptive use

27. Prevention Transmission can be reduced but not eliminated with the use of physical barriers such as condoms Study shows a reduction from abstaining from sexual activity Most cases and deaths from cervical cancer can be detected from a pap test

28. HPV Vaccines Two HPV vaccines are currently licensed in the United States The antigen in both is the L1 major capsid protein L1 self assemble into noninfectious, nononcogenic units called virus like particles (VLP) HPV4 vaccine is approved from females and males 9 through 26 years of age HPV2 vaccine is approved for females 10 through 25 years of age This is not approved for males

29. Vaccination Schedule and Use Routine vaccination at 11 or 12 with 3 doses of HPV2 or HPV4 Third does must follow first does by at least 24 weeks Vaccination can be started at 9 years of age Catch-up vaccination recommended for females 12 through 26 Males 22 to 26 may be vaccinated All immunocomprimised males (including HIV infection) and men who have sex with men through 26 years of age should be vaccinated An accelerated scheduale using minimum intervals is not recommended Series does not need to be restarted if the schedule is interrupted

30. Contraindications and Precautions Contraindication Severe allergic reaction (anaphylaxis) Precaution Moderate or severe acute illnesses ( defer until symptoms improve)

31. Vaccination during pregnancy Vaccination should be delayed until completion of pregnancy If pregnant after starting the series, remaining doses should be delayed If a vaccine is given during pregnancy, no intervention is indicated

32. Adverse Reaction Most common reaction are local reactions as site of injection (pain and swelling in 20-90% of patients) Fever is developed 10-13% of patients Reports of fever did not increase with increasing doses No series adverse reactions have been associated with this vaccination Other less severe reactions include nausea, dizziness, myalgia and malaise Patients should always be seated while administering vaccines and should be observed for 15-20 minutes after

33. Resources http://www.bristol.ac.uk/biochemistry/gaston/HPV/hpv_information.htm#lifecycle http://www.mayoclinic.org/diseases-conditions/hpv-infection/basics/tests-diagnosis/con-20030343 http://www2a.cdc.gov/stdtraining/ready-to-use/Manuals/HPV/hpv-slides-2013.pdf http://www.cdc.gov/vaccines/pubs/pinkbook/hpv.html#prevention