HPV: Prevention, Screening and Management

1. HPV: Prevention, Screening and Management Mary E. Arens, MS, PA-C Henry Ford Macomb Hospital Clinton Township, Michigan Women’s Healthcare Specialist

2. HPV Objectives • Epidemiology and Incidence of HPV. • Risk factors for HPV. • Screening and Management of HPV • Clinical manifestations and Diagnosis of HPV. • High-risk types of HPV • Cervical Cancer. • Prevention of HPV

3. Epidemiology • In 2012: 12,170 new cases of invasive cervical cancer. • HPV 16, 18 • 70% of cervical cancer • 50% precancerous lesions (CIN 2/3) • 72% Anal cancer • 69% precancerous anal lesions (AIN 2/3) • HPV 6, 11 • 90% of genital warts

4. HPV Incidence • Over 30-40 types in genital tract • 75-80% of sexually active adults will acquire a genital HPV infection by 50 • Most prevalent age 15-25 • Most infections are transient and asymptomatic • HPV infections clear 1-2 year • 10-20% have persistent infections • Progression to cervical cancer requires persistent infection over many years

5. Natural History HPV

6. HPV Risk Factors • Early age of first intercourse (<17 yrs) • Multiple sexual partners (>2) • Smoking four-fold risk of cancer • Other STD’s (i.e., Chlamydia,) • Male partners with multiple sexual partners • High-Risk HPV Positive pap smear • 16, 18 • Immunosuppressant (HIV, organ transplant, etc.)

8. Screening for HPV • Pap smears: 70% reduction in Cervical Cancer. • Conventional pap smear (Sensitivity 70-80%) • Thin Prep liquid base (Sensitivity 85-90%) • Both are acceptable. • Initial screening: • Age 21 Regardless of risk factors • Under 21 if high risk: • sexually active and Immunosupressed: HIV+, organ transplant, immunosuppressive therapy (ACOG)

9. Frequency of Screening • Under 30 years low risk • Every 3 years (ACOG 2012) • 30 years and older low risk • ACOG 2012 & ACS • Pap + HPV every 5 years (preferred) • USPSTF • Pap every 3 years

10. Frequency of Screening • Continue Annual Screening High Risk (ACOG, ACS) • History of Cervical Caner • History of CIN2 or CIN3 • Diethylstilbestrol (DES) exposure in utero • Can cause cancer • Immunocompromised patients: • HIV, SLE, organ transplant, on immunosupressive therapy, etc..

11. Frequency of Screening • Hysterectomy - • Benign conditions can discontinue • No history of CIN2/3 or Cancer • History of uterine or cervical cancer continue annual screenings. • Discontinue papsmear age 65-70 • If 3 or more normal papsmears • Two negative co-test (Papsmear+HPV) • Either with in the previous 10 years.

12. Papsmear Results • Bethesda Classification System (2001) • Conventional smear or Thin Prep Liquid based. • Satisfactory for evaluation • includes cells from the endocervical /transfomation zone • No obscuring blood or inflammation • Negative for intraepithelial lesion

13. Bethesda Classification • Other findings: • Trich, Candida, bacteria vaginosis, etc. • Treat • Atypical Squamous cell of undetermined significance (ASC-US) Reflex HPV Triage • Atypical squamous cells cannot exclude High-grade lesion (ACS-H)

14. Bethesda Classification • Low-grade squamous intraepithelial lesion (LSIL) • Biopsy findings: • HPV • mild dysplasia (CIN-1) • High-grade squamous intraepithelial lesion • Biopsy finding: - Closer to the basement membrane • Moderate (CIN 2) • severe dysplasia, carcinoma in situ, (CIN 3)

15. Bethesda Classification • Squamous cell carcinoma • Atypical glandular cells (AGC) or Atypical glandular cells-favor neoplastic: • Endocervical, endometrial sampling or NOS • HPV typing triage • Endocervical adenocarcinoma in situ (AIS) • Adenocarcinoma

16. HPV Testing • Primary HPV testing <30 • increase HPV infection • unnecessary colposcopies • Adding HPV to Pap smear >30 • earlier diagnosis of high-grade lesions • Adding HPV testing • Increases +HPV results and colposcopies

19. High-risk HPV • High Risk types: Most Common HPV (16, 18, 45, 31, 33, 52, 58, and 35 ) they have more oncogenic potential (95%). • Low & high-grade cervical changes (LSIL,HSIL,ASCUS-H) • Cervical intra-epithelial neoplasm (CIN2-3) • Cervical Cancer • Anal, vulva and vaginal cancers

21. Low-risk HPV • Low-risk: (most common)HPV(6,11,26,42,44,54,70,73) • Benign low-grade cervical changes (LSIL or CIN 1) • Condyloma acuminata (genital warts) • Less likely to progress to cervical cancer

22. HPV cytology • HPV infects the epithelial cells and mucous membrane. It is found with in the nucleus and replicates

23. Clinical presentation • Present as: • No clinical signs • Vulvar puritis, itching, burning, or pain • Condyloma (biopsy of suspicious lesion) • Cervical/vaginal squamous intraepithelial lesion (abnormal pap smear /cytology) • Cervical/vaginal intraepithelial neoplasm (CIN, VAIN) (histological biopsy) Abnormal Pap Management

24. Abnormal pap evaluation • ASC-US use Reflex for High Risk (HR) HPV • Positive HR HPV • >21 years (Colposcopy) • If pregnant no ECC • Negative HR HPV • 21-29 years (Repeat pap 3 years) • 30-65 years (Screen pap/HPV 5 years)

25. Abnormal pap evaluation • LSIL – low grade • >21 years Colposcopy • <21 years repeat papsmear 12 months • HPV not useful, assume HR neg HPV • HSIL, ASC-H, Cancer – high grade • Colposcopy and ECC

26. Abnormal pap evaluation • Atypical glandular cells (AGC) or Endocervical, endometrial sampling or NOS • <35 yrs need colposcopy & endocervical curettage (ECC) • if abnormal bleeding or obesity also need endometrial biopsy. • >35 yrs need colposcopy, ECC and endometrial biopsy.

27. Genital condyloma • Prevalence: 1% of sexually active adults. • Most commonly in posterior introitis, labia minora and majora. • Single or multiple papules, flesh-gray colored, smooth or rough edges. • Acetic acid 3-5% (Vinegar) applied to affected areas causes coagulation of epithelial cytokeratins and forms acetowhite lesion for identification for biopsy and for treatment.

28. Picture of genital warts

29. Treatment of genital warts • No one treatment is superior to the other. • Patient applied: must educate on proper use. (neither to be used during pregnancy) • Aldara (imiquimod 5% cream) Immune modular. Local immune response with HPV specific killer T-cells. • Podofilox (0.5% solution) mitotic poison • Physician applied: • TCA/BCA caustic agent, destroys tissue (weekly application needed) • Cryotherapy, causes cytolysis • Surgical excision or laser treatment

30. Cervical Cancer & HPV • In 2012: 12,170 new cases of invasive cervical cancer. • 4,030 women will die from cervical cancer. • HPV16 &18 cause (50%, 20% respectively) • Persistent high-risk HPV infection increases risk of developing cancer. • Not all high-risk HPV infections lead to cancer. • HPV is also responsible vulva, anal, penile and oropharyngeal cancers.

31. Prevent HPV infection • Abstinence is most effective • Condoms, do not cover all areas. But have been found to decrease cervical neoplasm and genital warts.

32. Prevent HPV infection • Vaccine (93-100% effective prevention) • Best given prior to HPV exposure. • Cervarix • Bivalent HPV (16,18) • (0,1,6 months) • Gardasil • Quadravalent HPV (6,11,16,18) • (0,2,6 months)

33. HPV Vaccine • Side effects: • Mild pain, erythema at injection sites. • Fever, fatigue headache and myalgia (uncommon) • Vaccine pregnancy category B, but not recommended • Vaccine is a preventive tool, not a substitute for cancer screening.

34. ACIP Vaccine Schedule 2012

36. Summary • Educate about HPV! • Very easy to acquire • High-risk HPV types and cervical cancer • Preventative methods. • Limit the exposure to HPV • Vaccine vs. barrier • Vaccine has been shown to be highly effective and very safe.

37. Remember the importance of screening with pap smears. • Follow-up on abnormal results. Thank you!