HPV vaccination 2013 to prevent cevical cancer in Lesotho
Preventing Cervical Cancer in Lesotho Sejojo Phaaroe Principal Biomedical Scientist, and a Cytologist of International Academy of Cytology- # 6467 Health Research & Laboratory Services Cytopathology unit – Lesotho
Learning out come• Learn and share: comprehensive review of international conventions on cervical cancer prevention & Lesotho ‘ s response• Cervical Cancer Prevention strategies• Aetiology of cervical cancer development and role of HPV• HPV What is it ?• HPV VACCINE – Gardasil , What is it?• EPI challenges:
There is no need for you to catch the ball if you do not know where the goal is -
Comprehensive review of international conventions on RH cancers IUAC ( International union Against Cancer) IUCR ( International Union on Cancer Research ) IAC (International Academy of Cytology) WHO (2002) - …AU ( Maputo SRH declaration) …SADAC …Lesotho Road map ( Maternal Mortality SRHR) WHO, 2002 AFROX declaration (2007)
1- WHO/ MOHSW – sponsor a baseline study CACX 20062. Lesotho RH Cancer Screening Guidelines3. Implementation of prevention guidelines Gardasil ACCESS : 2009 Pilloting Leribe and
African Conference on CervicalCancer Prevention Sept. 2010
Lobbying for Support from African Policymakers and Parliamentarians: The Uganda Experience Honorable Sarah Nyombi Member of Parliament, Uganda
• •Lesotho strategy: Involve policymakers (parliamentarians).• • Financial resources for new technologies (i.e., HPV DNA testing at point of care, vaccine).• • Training and education.• • Screening—VIA/cytology/DNA/colposcopy (pilot studies and full-scale HPV Vaccine rollout).
WHO- Public HealthLabtests? Radiology, urology Oncology, palliative care ? Etc problem (Stjernsward, 2007)
Distribution Of Common Cancer Between the Sexes IN Southern Africa to include Lesotho Males Females Lung Cervical Prostate Breast Stomach Lung Liver Stomach Colorectal Colorectal Oesophagus
Cancer definition Cancer is a neoplastic proliferation of abnormal cells, invading surrounding tissue and giving distance metastases Cancer of the cervix is the neoplastic proliferation of cells and tissues in the breast Abnormal proliferation starts with the genetic aberration in a single cell genetic material, which grows and give a clone of abnormal cells A number of factors contribute into the cellular disturbance ( later )
Signs and symptoms/ clinical presentation• Early signs:• Abnormal vaginal bleeding which could be• Intermenstrual• Post coital bleeding• Post menopausal bleeding• Watery offensive vaginal discharge• The cervix is friable , hard with contact bleeding on examination( the dysplastic cells have poor cohesiveness, so the underlining vascular system in the lamina propriae become exposed.)
Late signs• Pain• Dyspareuria(pain during intercourse)• Urinary symptoms: frequency in urination• Dysurea• Hematuria• Vesico-vaginal and or recto-vaginal fistula• Anaemia, Cachexia• Bone pain, due to metastases
Cervical Cancer Worldwide Disease Burden• 2nd most common cancer in women worldwide• Number one cause of cancer-related deaths in women in the developing world• Annual disease burden – 493,000 cases – 273,500 deaths• 80% of cervical cancer cases in the developing world
Lesotho Disease Burden• QEII data – 1April2006 – 31March2007 – 680 cervical cancer referrals – If 25-33% of population seek out treatment at the national referral hospital then 2000-2800 women may have late stage disease in Lesotho• Leribe and Mohale’s Hoek Referrals* – 1Jan2005 – 31March2006 – Retrospective analysis of cytology and hystology archives – Age Standardized Incidence Rate (ASIR) 66.7:100,000 women
Cervical Cancer by Age90% of cervical cancer cases were in women over age 39
Correlation of ASIR rates in Southern AfricaCOUNTRY ASIR Sited PublicationSouth Africa 32.1 : 100 000 Freddy Sitas et al 1993Mali 21.0 : 100 000 Bayo et al 1990Uganda 43.6 : 100 000 Wabbinga et al 1993Gambia 13 : 100 000 Bah 1990Senegal 9 : 100 000 Bah et al 1988Lesotho 66.7 : 100 000 S. Phaaroe et al 2007Senegal & Gambia are Moslem areas( Low in Gambia)Zimbabwe 67:100 000 ( Dr Cronje – Oncology specialist : SebetaMemorial Lecture LMA AGM 8/7/06
Prevention Strategies Education , BCC, condom distribution , and awareness campaigns PAP smear screening HPV DNA testing Direct Visual Inspection Acetic acid –VIA VIAM HPV vaccine- CAMPAIGN
S. Phaaroe National stake holders C.T(IAC), MIBMS M.T PSBH- REPORT Boston Education/Information-Magnitude of cancer University 2005 Well women groups/ church/ Gyaenacology, women in Law, Oncology, every body, Radiology, Support groups/ Pharmacy etc men leagues Chiefs, local government, FAMILY H, ED, CYTOPATHOLOGY village councils, PLANNING & BIOMEDICAL NETWORKS Men’s clinics, SCIENCE private clinics RESEARCH LAB linkage with is the central TechnologyLBCN NGO’S in a health organ INCUBATION system CENTRES, SMME’s , Joined Bilateral LEGAL EMPLOYMENT commissions/ Education , agreements Academic centers SYSTEMS, Policy FORCE/ of excellence & makers, Government other Research International Institutions institutions conventions, Insurance Levy, Regional Businesses & strategies Industry
Etiological factors behind cancer of the Cervix .Hormonal contraceptives• women -Early coitus /preparations like depo [Stern et al 1977]• Multiparious women • STI’s- infection, etc.• Multisexual partners • Viral HIV,• It varies with race [genetic 81% ? susceptibility ,etc] • Viral HPV,• High in low socio-economic stata • Viral H Herpes • [malnutrition,poor health facilities] Smoking [TARR/hetero]• Poor hygiene[smegma factor] • Alcohol drinking• Sperm factor[acridine histones] • Drugs (Diethylstilbestrol-• Women with boyfriends with CA. DES),cyclophosphamide penis • Pelvic irradiation. • History of cancer from other sites e.g uterus, colon.
Human Papillomavirus (HPV) and the Vaccine•• HPV is the most common sexually transmitted infection• DNA VIRUS• Causes 99% of cervical cancer cases worldwide• 100 different types of HPV, 40 types affect the genital tract• Types 16 & 18 cause 80% of cervical cancer cases
Disease Burden HPV types 6, 11, 16, & 18HPV Type Approximate Disease Burden 70% of cervical cancer, AIS, CIN 3,16 and 18 VIN 2/3, and VaIN 2/3 cases 50% of CIN 2 cases 35%–50% of all CIN 1, VIN 1,6, 11, 16, and 18 and VaIN 1 cases 90% of genital warts cases
GARDASIL® (Quadrivalent Human Papillomavirus [HPV Types 6, 11, 16, 18] Recombinant Vaccine) Classification of Histological Findings CIN 1 CIN 2 CIN 1 (mild (moderate CIN 3 Invasive CIN1 Normal (condyloma) dysplasia) dysplasia) (severe dysplasia/CIS) Cancer Histology of squamous cervical epithelium1 Basal cell Basal membrane CIN caused by HPV can clear without treatment; however, rates of regression are dependent on grade of CIN.
Screening for cervical cancerDr. George N. Papanicolaou, who devised the "Pap" smear test for cancer,examines a slide in his laboratory in 1958. NOVA, PBS
GARDASIL® (Quadrivalent Human Papillomavirus [HPV Types 6, 11, 16, 18] Recombinant Vaccine) Cervical Transformation Zone • Area of metaplasia at squamocolumnar junction • ~99% of HPV-related genital cancers arise within the transformation zone. • The Pap test obtains cells from the transformation zone for cytology screening. 1. Castle PE. J Low Genit Tract Dis. 2004;8:224–230. 2. American Cancer Society. Prevention and early detection. Pap test. July 2006; Available at; http://www.cancer.org/docroot/PED/content/PED_2_3X_Pap_Test.asp?sitearea=PED
GARDASIL® (Quadrivalent Human Papillomavirus [HPV Types 6, 11, 16, 18] Recombinant Vaccine) Appearance of the Normal Cervix on VIAM 1. Sellors JW, Sankaranarayanan R, eds. Lyon, France: International Agency for Research on Cancer; 2003. Reprinted from Colposcopy and Treatment of Cervical Intraepithelial Neoplasia. A Beginner’s Manual with permission of the International Agency for Research on Cancer, World Health Organization.
GARDASIL® (Quadrivalent Human Papillomavirus [HPV Types 6, 11, 16, 18] Recombinant Vaccine) Invasive Cervical Carcinoma From IARC, 2003.1
Interpretation• Pick up age for HPV _>19 -44 yrs• Pick up age for other specific infections= ->19-44• Peak age for CIN1= 20-39 yrs• Peak age CIN2 = 30-49 yrs• Peak age for CIN3= 35-44 yrs• Pick up for invasive cancer= 30- 59 CYTOLOGICALLY• Peak age for confirmed invasive cancer = 40-59 yrs• Risk of women developing cancer= (36:4610)• Risk = 1: 128 women• ASIR: 66,7 : 100 000
HPV Type Prevalence WorldwideClifford GM, Smith JS, Plummer M, Munoz N, Franceschi S. Human papillomavirus types in invasivecervical cancer worldwide: a meta-analysis. Br J Cancer. 2003;88: 63-73.
High prevalence of HPV 16 in South African women with cancer of the cervix andcervical intraepithelial neoplasia• Cervical cancer biopsies 82% contained type 16 and 10% type 18• 56.6% of CIN (cervical intraepithelial neoplaysia) lesions contained type 16 Kay P, Soeter R, Nevin J, Denny L, et al. High prevalence of HPV 16 in South African women with cancer of the cervix and cervical intraepithelial neoplasia. J Medical Virology 2003;71:265-273.
Gardasil®• Non-infectious, recombinant, quadrivalent vaccine• Prepared from highly purified virus-like particles (VLPs) of the major capsid protein (L1) protein• Contains no DNA• Protects against HPV types 6, 11, 16 & 18• Three separate IM injections – 1st dose: at elected date – 2nd dose: 2 months after the 1st dose – 3rd doses: 6 months after the 1st dose
Gardasil® Registration• Registered in more than 100 countries• U.S., all 27 member countries of the European Union, Mexico, Australia, Taiwan, Canada, New Zealand, and Brazil• U.S. FDA approval in June 2006• Africa registration: South Africa, Togo, Chad, Uganda• when we first stated vaccinating , 26 million doses distributed worldwide• 11 million doses distributed in the U.S.
Clinical Trials• FUTURE I & FUTURE II studies• Phase III, prospective, double-blind, placebo controlled trials in 29 countries• Females ages 15 - 26
GARDASIL® [Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine] GARDASIL Is Efficacious Against HPV 16– and 18–Related CIN 2/3 or AIS GARDASIL Placebo 60 53 50 40 n=8,460 Related Cases 30 100% 20 Efficacy 10 n=8,487 0 0 CIN 2/3 or AIS 16- to 26-year-old females naïve to the relevant vaccine HPV type at enrollment and through 30 days Postdose 3 Over a period of 2 to 4 years Analysis included Protocol 005. CIN = cervical intraepithelial neoplasia; AIS = adenocarcinoma in situ. 54
GARDASIL® [Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine] GARDASIL Is Efficacious Against HPV 6/11/16/18–Related VIN and VaIN GARDASIL Placebo 12 10 10 8 Related Cases n=7,741 6 100% 4 Efficacy 2 n=7,769 0 0 VIN 2/3 or VaIN 2/3 16- to 26-year-old females naïve to the relevant vaccine HPV type at enrollment and through 30 days Postdose 3 Over a period of 2 to 4 years VIN = vulvar intraepithelial neoplasia; VaIN = vaginal intraepithelial neoplasia. Data available on request from Merck & Co., Inc., Professional Services-DAP, WP1-27, PO Box 4, West Point, PA 19486-0004. Please specify information package 20651717(3)-GRD. 55
GARDASIL® (Quadrivalent Human Papillomavirus [HPV Types 6, 11, 16, 18] Recombinant Vaccine) HPV and Anogenital Warts HPV 6 and 11 responsible for >90% of anogenital warts Infectivity >75% Treatment can be painful and embarrassing.4 Topical and surgical therapies are available for genital warts Recurrence rates vary greatly. 1. Jansen KU, Shaw AR. Annu Rev Med. 2004;55:319–331. 2. Soper DE. In: Berek JS, ed. Novak’s Gynecology. 13th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2002:453–470. 3. Lacey CJN. J Clin Virol. 2005;32(suppl):S82–S90. 4. Maw RD, Reitano M, Roy M. Int J STD AIDS. 1998;9:571–578. 5. Kodner CM, Nasraty S. Am Fam Physician. 2004;70:2335–2342. 56
HPV Clearance In a study of 608 college women, 70% of new HPV infections cleared within 1 year and 91% within 2 years. Median duration of infection = 8 months Certain HPV types are more likely to persist (eg, HPV 16 and HPV 18). Women with HIV are unable to clear the infectionSchiffman J Natl Cancer Inst Monogr. 2003;31:14–19.Ho N Engl J Med. 1998;338:423–428. 58
Cervical Cancer and HIV CIN is common in HIV infected women because: HIV infected women likely to have persistent HPV Persistent infection leads to cervical cancer Do ARTs Lower the Risk of Cervical Cancer? Multiple studies yield mixed results Incidence of cervical cancer appears to be unchanged in the ART era Those on ART are more likely to have persistent HPV So, probably no . . . therefore other treatment needed 59
GARDASIL® [Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine] GARDASIL Is Efficacious Against HPV 6/11/16/18–Related Lesions GARDASIL Placebo 100 91 90 83 80 70 60 n=7,861 n=7,899 Related Cases 50 95% 99% 40 Efficacy Efficacy 30 20 n=7,858 n=7,897 10 4 1 0 CIN 1, CIN 2/3 or AIS Genital Warts 16- to 26-year-old females naïve to the relevant vaccine HPV type at enrollment and through 30 days Postdose 3 Over a period of 2 to 4 years CIN = cervical intraepithelial neoplasia; AIS = adenocarcinoma in situ. 60
Lesotho HPV Vaccination Strategy• Application for Gardasil access 2008• Establishing National HPV Guidelines, action plan, implementation strategy• The HPV Vaccine was be piloted in Leribe and Mohales’Hoek districts• Target population: Females Aged 9-18 years, later 9-13 yrs• School-based was used Estimated Starting period : February 2009• Follow established vaccine distribution system• Monitoring and evaluation- through current system