hpv and cervical cancer screening vietnam longer (eng)

HPV Vaccine and Cervical Cancer Screening Rebecca Jackson, MD Associate Professor Obstetrics, Gynecology & Reproductive Sciences and Epidemiology & Biostatistics San Francisco General Hospital Preview  Effectiveness of HPV vaccine (in the US)  Effectiveness of Cervical Cancer Screening Programs  Which to choose? Part 1 Effectiveness of HPV vaccine in screened populations HPV and Cervical Cancer  Cervical cancer is due to persistent high risk HPV infection  67%: HPV types 16 & 18  33%: other high risk HPV types (30s, 40s, 50s)  Infections are sexually acquired in teens, twenties  Most HPV infections are transient  Genital warts: caused by HPV 6 & 11 HPV Vaccine  Logic for vaccine  Once HPV infection cleared, immune to HPV type  16 & 18 antigen: prevent cervical cancer  6 & 11 antigen: prevent genital warts  Merck Gardasil quadravalent vaccine active against HPV 6,11,16,18. Gardasil HPV Vaccine  FDA approved in June 2006  Contains virus-like particles (not live virus)  3 shots: 0, 2 and 6 months  Booster shot?: high titers for 5 years of study, but no longer term data so don’t know if need booster shot. Gardasil Study Populations Per Protocol Efficacy  HPV seronegative at entry  HPV DNA (PCR) negative during vaccination phase  All 3 injections completed  No protocol violation  Case counting 1 month after dose 3 General Population Impact  Seropositive or seronegative on day 1  73% negative for all 4 types  20% positive for 1 type  <1% positive for all 4 types  Any PCR + during vaccination phase  Any Pap>ASC-US on day 1  Protocol violators Gardasil Study Populations Per Protocol Efficacy  Best case scenario  Maximum effectiveness General Population Impact  How the vaccine would work in a real population including women already sexually active (some HPV positive)  Minimum effectiveness Terminology of abnormal cervical lesions Main outcomes of study were: 1. Decrease in advanced (high-grade) cervical lesions due to HPV 16/18.  Called “CIN 2/3 and AIS” 2. Decrease in high and low grade cervical lesions due to HPV 16/18  Called “CIN 1/2/3 and AIS” 3. Decrease in warts due to HPV 16/18 Gardasil Efficacy* Studies Vaccinated vs. Placebo Efficacy against lesions at 3-4 years Per Protocol Efficacy (virus naïve only) CIN 2/3 + AIS* 100% (93-100%) CIN 1/2/3 + AIS* 95.2% (87-99%) Genital Warts 98.9% (94-100%) *Only lesions due to vaccine HPV types; does not *Only lesions due to vaccine HPV types; does not include disease due to nonvaccine HPV types include disease due to nonvaccine HPV types [...]... be worth it although cervical cancer screening alone has been very effective in reducing incidence and mortality The main benefit in a well-screened population will be in decreasing preinvasive lesions What about in a population with less effective screening? Part 2 Effectiveness of Cervical Cancer Screening Programs Cervical Cancer: Nat’l History Pap smears are the most effective screening test ever... exposed to HPV? Vaccine will not affect progress of an already acquired HPV infection (it is prophylactic, not therapeutic) But, if < 26 years and < 4 sexual partners, 73% are virus naïve; so vaccine can still be moderately effective From the population impact study: 39% HPV 16/18 CIN 2+ 12% ▼all HPV type CIN 2+ HPV Vaccine can’t replace screening (in the US) 1/3 of cervical cancers due to HPV types... Decrease Cervical Cancer Rates 2006 US rates of cervical cancer Incident cases per year: 9,710 Deaths: 3,700 HPV vaccine will not prevent all of these cases Some US women will choose not to be vaccinated Many immigrant women will not be vaccinated Some develop cervical cancer even if vaccinated Conclusions Optimistic: “Vaccine saves women’s lives” Pessimistic: “Vaccine is unnecessary because cervical cancer. .. AIS* 95.2% 46.4% Genital Warts* 98.9% 68.5% CIN 2/3 + AIS* 39.0% *Only lesions due to vaccine HPV types; does not include disease due to nonvaccine HPV types What about cervical lesions not due to 16/18? Vaccine only active against 16/18 but 20 other HPV types also cause cancer What if suppressing HPV 16 and 18 allows these other viruses to multiply? (This is called replacement) So, what we really... not controversial The natural history of cervical cancer is wellunderstood and begins with a pre-invasive lesion (dysplasia) that is easily detectable and treatable Development of invasive cancer occurs in an orderly progression from low grade to high grade dysplasia to invasion This process takes about 10 years Pap smear screening: the process Pap smear (cervical cytology) done by obtaining cells... adverse experiences Benefits of Quad HPV Vaccine Decrease cervical cancer cases and death rates Reduce hysterectomies, radiation treatment, infertility Reduce loss of productive years of life Decrease cases of external genital warts Less physical discomfort, stigmatization, cost Decrease need for colposcopy, treatment of SIL Fewer false positive Paps Less detection and treatment of pseudodisease (non-progressive... be cost effective in conjunction with reduced screening Unclear cost/benefit in countries without effective screening programs in place The benefits of HPV vaccine are decades away due to natural history of the disease and due to time required to implement a vaccination program Barriers to HPV immunization in developing countries Takes an average of 10-20 years to bring new vaccine to developing countries... warts here in Viet Nam Reduce (Unnecessary) Evaluation and Treatment False positive Pap smears ASC-US: 3-10% have CIN 2/3+ LSIL: 10-20% have CIN 2/3+ Vaccine expected to sharply reduce transient high risk HPV infections that cause abnormal Paps But, the false positives do not become cancer Conclusions Vaccine prevents invasive diagnostic evaluation and treatment This only applys in a screened population... vaccine There was no clear evidence of protection from disease caused by HPV types for which subjects were PCR positive and/ or seropositive at baseline Individuals who were already infected with 1 or more vaccine-related HPV types prior to vaccination were less likely to develop clinical disease caused by the remaining vaccine HPV types Is it safe? Injection site (1-5 days postvaccination) Gardasil... than 16 and 18 Vaccine is not 100% effective Not all will receive it Unclear if replacement of HPV 16/18 by other virus types will occur thus decreasing the benefit of the vaccine Vaccine Cost? One of the most expensive vaccines ever US $360 for 3 courses (does not include administration fees) In the US, cost effectiveness analyses show it can be cost effective in conjunction with reduced screening . of HPV vaccine (in the US)  Effectiveness of Cervical Cancer Screening Programs  Which to choose? Part 1 Effectiveness of HPV vaccine in screened populations HPV and Cervical Cancer  Cervical. HPV Vaccine and Cervical Cancer Screening Rebecca Jackson, MD Associate Professor Obstetrics, Gynecology & Reproductive Sciences and Epidemiology & Biostatistics San. twenties  Most HPV infections are transient  Genital warts: caused by HPV 6 & 11 HPV Vaccine  Logic for vaccine  Once HPV infection cleared, immune to HPV type  16 & 18 antigen: prevent cervical