Cervical cancer Because the vaccine is not the

Cervical cancer: Because the vaccine is not the worst case scenario Jennifer L. Young, MD, MPH National Organization for Women Panel September 23, 2008

Objectives • Answer 2 questions – Is cervical cancer worth preventing? – How do we prevent it – the easy way or the hard way?

Epidemiology of cervical ca • 11, 070 new cases each year • 3, 760 deaths from cervical ca • Risk factors same as for HPV infection for majority of patients – Early age of sexual debut – Multiple sexual partners – Smoking – HIV – History of sexually transmitted disease • 50% higher risk in black compared to white

Risk factors for cervical cancer • Risk of HPV – Lifetime risk for women 80% • Not having adequate screening – No pap smear in last 3 years – Decreased access to medical care • Immunosuppressed – HIV – Diabetic – Other

Cervical cancer by state

Incidence of cervical cancer by race in Virginia

HPV disease incidence by patient age http: //content. nejm. org/content/vol 353/issue 20/images/large/01 f 2. jpeg

Risk Factors for Female Genital HPV Infection • Sexual behavior of her male sexual partners ü Risk increased if he has had > 3 partners 1 ü Risk increased if he has had a same sex partner (s) [bisexual contact(s)]. • Increased number of male sexual partners (>3)1 ü (increases the risk of encountering an HPV infected male !) • Sexual Intercourse at a young age (before the age of 24 in the U. S) -the maturing cervical epithelium (T-Zone) is felt to be more easily infected by HPV. 1. Ley et al. J Natl Cancer Inst. 1991. 83. 997

Other Possible Mechanisms of HPV Transmission & Infection • Non-Sexual Transmission – Mother to newborn [respiratory tract papillomatosis] (vertical transmission)2 – Skin to skin (thought to require breaks in skin surface) 1. 2. Winer RL, et al. Am J Epidemiol. 2003: 157: 318 -226 Smith EM et al. Sex Transm Dis. 2004. 31; 57 -62.

Cervical cancer prevention • Pap smears performed once per year until age 30 • >30 yo- once every 3 yrs if pap and HPV negative • 75% reduction in cervical cancer in countries with adequate screening • At what cost? – 3 million abnormal pap smears a year – 300, 000 high grade dysplasia – 11, 000 cervical cancers

Financial burden of HPV disease in the US 1

Emotional cost • Most women describe feelings of being dirty or unclean after the diagnosis of an abnormal pap smear – Decreased sexual drive – Poor self image – Decreased feelings of intimacy with their partner

What is the treatment for an abnormal pap smear? • Microscopic examination of the cervix for abnormal cells • Removal of the abnormal cells – Laser – Freeze abnormal cells – Excise abnormal cells with a scalpel or by burning

Costs to society • Risks of cervical procedures – Cervical scarring – infertility – Cervical weakening – pregnancy risk • 2. 5 x increased risk of preterm labor • 2. 5 x increased risk of low birth weight • 3 x increased risk of cesarean section

Cervical Cancer Treatment • Surgical management – Radical hysterectomy with lymph node removal – Goal is removal of all tumor – If LN positive – pt will need postop radiation • Chemoradiation – External beam radiation – usually 25 days – Weekly chemotherapy – Internal radiation 2 -6 days

Complications of treatment • Gynecologic – Vaginal scarring – Poor sexual function – Menopause • Gastrointestinal – Chronic diarrhea – Bowel obstruction – Fistula • Urologic – Blockage of ureters with kidney failure – Hemorrhagic cystitis – Fistula • Other – Chronic back pain – Skin changes – Lymphedema in legs

Lymphedema

Recurrent cervical cancer • 30% of cervical cancers will recur and most are fatal – If metastatic treated with chemotherapy – If localized, one potentially curative option • Pelvic exenteration curative 50% of the time

Conclusions • Cervical cancer affects women in our community • Cervical cancer is a serious disease – Risks just from preventing cancer – 30% mortality from cervical cancer – Long term effects after treatment for cervical cancer • Cervical cancer is preventable – Regular pap smears – HPV vaccination

HPV Vaccination: Hot Topics Jennifer L. Young, MD, MPH University of Virginia September 23, 2008

HPV Vaccine Safety Information obtained from the CDC VAERS website • NO PROVEN ASSOCIATION of death from Gardasil – 21 deaths occurred after Gardasil vaccine – 12 investigated and found to be unrelated – 5 no patient identification in the report thus unable to be investigated – 4 in foreign countries, unable to be investigated

HPV Vaccine Safety Information obtained from the CDC VAERS website • Guillan-Barre Syndrome (GBS) – Neurologic illness occuring after viral infection in 12/100, 000 teenagers – 44 reported cases after Gardasil vaccination • 42 in US, 2 in foreign countries – – – 13 confirmed 9 pending follow-up 8 did not meet criteria for diagnosis 11 unconfirmed 1 had symptoms prior to vaccination – NO PROVEN ASSOCIATION • Rate is within range of that which would be expected by chance alone

Mandating the HPV vaccine • Racial differences in vaccination rates may widen the gap • Mandate for your doctors

National Coverage with 4: 3: 1: 3: 3: 1 Series by Race/Ethnicity Childhood vaccination racial disparities: closing the gap 1. CDC. MMWR September 5, 2008; 57(35): 961 -966.

Racial disparities in childhood vaccinations • Since 2005, the CDC notes that racial disparities in childhood vaccines are closing 1 – Largely attributed to Vaccines for Children (VFC) program – Remain large variation by state and between rural and urban – Virginia remains average with coverage rates 67 -91% • Study of Hep B school mandate 2 – Vaccination rates increased (85% vs. 37%) – Racial disparities decreased • Black vs. white (RR 0. 94 from 0. 70) • Hispanic vs. white (RR 0. 97 from 0. 88) 1. 2. CDC. MMWR September 5, 2008; 57(35): 961 -966. Morita JY et al. Pediatrics 2008; 121(3): e 547 -e 552.

HPV Vaccine Legislation • Funding allocations – 8 states considered – 3 states have passed • Educational campaigns – 24 states have considered – 14 states have passed • Mandatory insurance coverage – 18 states have considered – 5 states have passed into law (CA, CO, IL, NM, RI)

School mandates • Texas – Gov. Rick Perry signed Executive Order 4 Feb. 2, 2007 – H. B. 1098 reversed HPV mandate • New Mexico – HPV school mandate vetoed by the Governor • Virginia – HPV school mandate signed into law after revision – Increased ease of parental opt-out • District of Columbia – Mandate has passed City Council – Congressional review date has passed

Virginia school mandate • Only HPV vaccination mandate in the country • Signed into law April 2007 • Requires all girls to have initiated the HPV vaccination series prior to entry into the sixth grade starting October 2008 • Verbal parental opt-out • 3 bills introduced to overturn – All failed in committee in 2008 General Session

Debate continues in Virginia • 2008 General Assembly – HB 89 to repeal mandate – SB 722 to repeat mandate – HB 188 to delay mandate until 2010 • • • Out of committee with a 13/9 vote Passed the House 57/39 Defeated in Senate committee • School mandate to go into effect October 2008

“None of us is going to be satisfied if the only women getting the vaccine are the same women already covered by screening programs. ” - John Schiller National Cancer Institute

Paying for the HPV vaccine

Current Coverage of the HPV vaccine • 3 shot regimen costing $120/injection or $360 total • Coverage ≤ 18 years old – Public: Federal Vaccines for Children program for Medicaid qualifiers – Private: Most insurance companies cover but age range and reimbursements differ • Coverage > 18 years old – Public: Medicaid coverage of women 18 -21 at high risk – Private: Most insurance companies cover but age range and reimbursements differ

Cost effectiveness of HPV vaccine • < $50, 000 for QALY considered cost effective – Mammograms for breast ca $67, 000 QALY – PSA for prostate cancer screening $113, 000 • HPV vaccine in setting of current screening 1 – $3, 906 -$14, 723 per QALY – Lower if herd immunity achieved 1. Chesson HW. Emerg Infect Dis 2008 14(2): 244.

Future Information on Vaccines • Booster? • Older women? • Women with prior HPV disease?

Immunogenicity of vaccines Olsson SE et al. Vaccine 2007; 25: 4931.

Breaking news: Quadrivalent vaccine • Efficacy in HPV + women 1 – 100% effective in preventing CIN 2/3 from vaccine viral types for neg women – 94% effective in preventing vulvar/vaginal disease • Women aged 24 -452 - 1. 2. Study of 3819 women 67% naïve to 6, 11, 16, 18 Only 0. 7% of women + for >1 vaccine viral types FUTURE II Study Group. J Infect Dis 2007; 196: 1438. Makhija S, FUTURE III Investigators. Gyn Oncology 2008, abstract.