HPV Vaccination & Ca. Cervix Screening Update Dr. Sharda Jain Dr. Jyoti Agarwal Dr. Jyoti Bhaskar


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  • India’s population is approximately 1/6th of the world burden but the disease burden in India is more than 25%( 1/4th)
  • Key Point
    Incidence of cervical cancer cases in India is highest as compared to other cancers in women 15-44 yrs of age
    1) WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Summary report on HPV and cervical cancer statistics in India. 2007. [Accessed on 18th March 2008. Available at www. who. int/ hpvcentre c WHO/ICO Information Centre on HPV and Cervical Cancer
  • Key Point
    The end points used in clinical trials of QHPV Vaccine® [Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine] are the immediate precursors of cervical cancer―CIN 2, CIN 3, and AIS (adenocarcinoma in situ).
    Although the primary objective of vaccination with QHPV Vaccine is to reduce cervical cancer, ethical and time considerations make it necessary to use a surrogate end point in clinical trials of vaccine efficacy.1 The US Food and Drug Administration (FDA) and its Vaccines and Related Biologics Advisory Committee examined the natural history of cervical cancer to define surrogate markers for cervical cancer.2
    Nearly 100% of cervical cancers are caused by HPV infection,3 but the great majority of HPV infections clear before they become serious.1 So, HPV infection can be used as an end point for preliminary evaluations of vaccine efficacy, but not as definitive proof of cancer prevention. CIN 1 has the same limitation—it is the histologic counterpart to early HPV infection. 2
    The only surrogate clinical condition is biopsy-confirmed CIN 2/3 or AIS. These lesions are the obligate precursor to invasive cervical cancer and are always treated.1,2 Therefore, CIN 2/3 or AIS are strong surrogate markers for cervical cancer. A demonstration that HPV vaccination prevents the development of CIN 2/3 or AIS lesions caused by vaccine HPV types would constitute a demonstration that HPV vaccination prevents cervical cancer caused by vaccine HPV types.2
    1. Pagliusi SR, Aguado T. Efficacy and other milestones for human papillomavirus vaccine introduction. Vaccine. 2004;23:569–578.
    2. Pratt D, Goldenthal K, Geber A. Discussion of possible endpoints for licensure of human papillomavirus (HPV) vaccines [FDA briefing document #1]. Vaccines and Related Biological Products Advisory Committee Meeting, November 28-29, 2001. Available at: http://www.fda.gov/ohrms/dockets/ac/01/briefing/3085b1.htm. Accessed January 18, 2006.
    3. Franco EL, Harper DM. vaccination against human papillomavirus infection: a new paradigm in cervical cancer control. Vaccine. 2005;23:2388–2394.
  • Key Point
    The World Health Organization (WHO) Strategic Advisory Committee of Experts
    (SAGE) recommended the primary target population for HPV vaccination is likely
    to be girls 9 or 10 through 13 years of age in most countries.
    The 2009 WHO SAGE recommendations emphasize that vaccination against HPV is most effective when given to females naïve to infection with vaccine-related types. Therefore, the primary target population for vaccination should be based on age of sexual initiation and feasibility of delivery infrastructure to reach young adolescent girls (ie, through schools, healthcare facilities, community-based methods). For most countries, this population is likely to be girls 9 or 10 through 13 years of age.1
    1. World Health Organization. Meeting of the immunization Strategic Advisory Group of
    Experts, November 2008–conclusions and recommendations. Wkly Epidemiol Rec.
  • Key Point
    Higher neutralizing antibody responses were observed in female adolescents,
    compared with young adult women.
    This evaluation of anti-HPV levels induced by GARDASIL™ [Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine] in male and female subjects (N=12,343) showed that 1 month after the last vaccination (month 7) geometric mean titer (GMT) levels for all 4 HPV types were higher in younger female adolescents compared with older groups of female adolescents and young adult women.1
    This slide presents the serum anti-HPV 6 GMTs at month 7 by age at first vaccination in the per-protocol immunogenicity population 9 to 23 years of age (females 24–26 years of age were excluded due to the small numbers of subjects). All GMTs were measured using the same cLIA.1
    1. Giuliano AR, Lazcano-Ponce E, Villa L, et al. Impact of baseline covariates on the
    immunogenicity of a quadrivalent (types 6, 11, 16, and 18) human papillomavirus virus-like-particle vaccine. J Infect Dis. 2007;196:1153–1162.
  • Key Point
    Antibody response to Quadrivalent HPV vaccine is durable, as evidenced by data through 5 years postdose 1.
    Subjects from the Quadrivalent HPV vaccine and placebo arms of the original dose-ranging study were eligible to participate in an extension of the trial, which included scheduled visits for the collection of efficacy samples at months 54 and 60. In addition, subjects in the extension received an immune challenge at month 60 and provided serum samples for summarizing immunogenicity at month 60, and 1 week following month 60.1
    The purpose of the extension was to provide efficacy and immunogenicity follow-up through 5 years postdose 1 and to assess the impact of an immune challenge given 5 years following the first dose. Two hundred forty one subjects entered the extension phase, 222 of whom received an injection of Quadrivalent HPV vaccine at month 60. For subjects who received a primary series of Quadrivalent HPV vaccine in the base study, the month-60 vaccination was an immune challenge dose (102 subjects); for subjects who received placebo in the base study, the month-60 vaccination was their first dose of Quadrivalent HPV vaccine (119 subjects), to be followed by second and third doses at months 62 and 66, respectively.1
    GMTs and the corresponding 95% CIs for all time points through month 61 were calculated for subjects in the extension phase of protocol 007. In order to be eligible to be included in these summaries, subjects must have (1) received all 3 injections of their respective primary series of vaccine/placebo and a vaccination with Quadrivalent HPV vaccine at month 60, (2) had serology data within acceptable day ranges of 4 weeks following month 60, and (3) received no other HPV vaccine.1
    As shown in this slide, there is evidence of an anamnestic response to immune challenge. Represented here are immunogenicity results in subjects who were seronegative to the relevant HPV type at day 1 and PCR-negative to the relevant HPV type through month 60.1
    Anti-HPV responses were similar for HPV types 6, 11, and 18 through 5 years of follow-up in 16- to 23-year-old females in the same subset analysis.1
    References –
    1. Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine: Vaccine 25 (2007) 4931–4939
  • Study Design: By use of the Danish National Patient Register, we identified 16,155 men and 32,933 women who
    received a diagnosis of GW during 1978–2008. Standardized incidence ratios (SIRs) were computed as estimates
    of the relative risk of specific cancers or sites.
  • HPV Vaccination & Ca. Cervix Screening Update Dr. Sharda Jain Dr. Jyoti Agarwal Dr. Jyoti Bhaskar

    1. 1. HPV Vaccination & Ca. Cervix Screening Update Dr. Sharda Jain Director :- Sec General : Delhi Gynae Forum
    2. 2. What is the Disease burden of Ca. Cervix in India ?
    3. 3. India ~1,34,000 World ~ 5,29,000 India ~25% of new Cervical Cancer cases in world India ~ 73,000 World ~ 2,75,000 India ~25% Rest of World - 75% India ~27% of deaths due to Cervical Cancer in world Rest of World - 73% India - 27% Cervical Cancer – Disease Burden Incidence Mortality India ~27% Rest of World - 73% HPV and Cervical Cancer in the World. 2010 Report. WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Available at: www.who.int/hpvcentre
    4. 4. 72,825 Deaths Annually Approx. 200 women die every day Every 7 minutes a women dies Approx. 8 women die every hour Burden of Disease in India 1. WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Human Papillomavirus and Related Cancers in India. Summary Report 2010. [Accessed on 5th July,2010]. Available at www. who. int/ hpvcentre
    5. 5. Cancer Incidence India Women of all ages WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Human Papillomavirus and Related Cancers. Summary Report 2010. [Accessed on 5th July,2010]. Available at www. who. int/ hpvcentre
    6. 6. Death Due to Ca cervix • The cervical cancer death rate of 16 per 100 000 reported in table 2 suggests that a 30-year old Indian woman has about 0·7% risk of dying from cervical cancer before 70 years of age in the absence of other diseases. • By contrast, the risk of dying during pregnancy for Indian women aged 15–49 years is about 0·6%.31 30 yr old woman has more risk of dying due to cervical cancer than dying during pregnancy. 2. Dikshit et al, Cancer mortality in India: a nationally representative survey, Published online March 28, 2012 DOI:10.1016/S0140-6736(12)60358-4 www.thelancet.com
    7. 7. What is the Relation of HPV With Cervical Cancer ?
    8. 8. HPV 16 HPV 18 HPV 6 HPV 11 Cancer causing Types High risk group-16,18, 31,33,45,52,58 Non-cancer causing types Low risk group- 6,11. • >75% of Cervical Cancer5,6 • >50% of Vaginal & Vulvar Cancer5 90% of Anogenital warts5 HPV is a necessary cause of cervical cancer – 99.7%4 HPV 1.Schiffman M, Castle PE. Arch Pathol Lab Med. 2003;127:930–934. 2. Wiley DJ, Douglas J, Beutner K, et al. Clin Infect Dis. 2002;35(suppl 2):S210–S224. 3. Muñoz N, Bosch FX, Castellsagué X, et al. Int J Cancer. 2004;111:278–285. Reprinted from J Virol. 1994;68:4503–4505 with permission from the American Society for Microbiology Journals Department. 4. Walboomers JM, Jacobs MV, Manos MM, et al. J Pathol. 1999;189:12–19. 5. X. Castellsagué, S. de Sanjose, T. Aguado, K. S. Louie, L. Bruni, J.Muñoz, M. Diaz, K. Irwin, M. Gacic, O. Beauvais, G. Albero, E. Ferrer, S. Byrne,F. X. Bosch. HPV and Cervical Cancer in the World. 2007 Report. WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Available at: www.who.int/hpvcentre6. Bhatla N et al.Vaccine (2008;26; 2811-17 Human Papillomavirus (HPV) Need for multivalent HPV vaccine for broader HPV protection
    9. 9. HPV Vaccination: The Basis of Cancer Control World Health Organization, United Nations Population Fund. Preparing for the Introduction of HPV Vaccines: Policy and Programme Guidance for Countries. Geneva, Switzerland: World Health Organization; 2006. Palliative care Cancer treatment Secondary prevention: Screening and treatment of precancers Primary prevention: Vaccination
    10. 10. 0 5 10 15 20 25 20–24 25–29 30–34 35–39 40–44 45–49 50–54 55–59 60–64 Age Group (Years) HPV infection Cervical Cancer HPVPrevalence(%) CancerIncidenceRate(×105 ) 25 20 15 10 5 0 (n=3752) * Two different cohorts (cross-sectional study) followed during the same time span to measure the rate of high-risk HPV infection in one and the rate of cervical cancer in the other. 1. Adapted from Bosch FX, Lorincz A, Muñoz N, Meijer CJLM, Shah KV. J Clin Pathol. 2002;55:244–265, with permission from the BMJ Publishing Group. Peak of HPV infection Peak of cervical cancer Age-Specific Rates of HPV Infection & Cancer* Age for vaccination 9 – 26 years
    11. 11. Adapted from Pinto AP et al. Clin Obstet Gynecol. 2000;43:352–362. Natural History of HPV Infection: Surrogate Markers for Cervical Cancer 0–1 Year 0–5 Years 1–20 Years Invasive Cervical Cancer Cleared HPV Infection CIN 1 Initial HPV Infection Continuing Infection CIN 2/3 or AIS Primary efficacy objective of quadrivalent HPV vaccine program: Demonstrate prevention of HPV 16/18-CIN 2/3 + AIS CIN = cervical intraepithelial neoplasia. AIS = adenocarcinoma in situ.
    12. 12. • Quadrivalent vaccine can prevent HPV infection aiming at prevention of precancerous lesions & cervical cancer. • More than 25,000 women worldwide have been enrolled in trials across the globe in 33 countries. • Highly successful in preventing precancerous lesions & cervical cancer. • It has also been studied in Indian women as per local regulations. HPV Infection can be prevented 1. Mao C et al. Obstet Gynecol. 2006;107:18–27. 2. Villa LL et al. Lancet Oncol. 2005;6:271–278. 3. Garland SM et al. New Engl J Med. 2007;356:1928–1943. 4. The FUTURE II Study Group. New Engl J Med. 2007;356:1915–1927.
    13. 13. 1.Stanley M. Vaccine 2006; 24: S106-13, 2.Tindle, Nat Rev Cancer 2002; 2, 59, 3.Stanley M. Vaccine 2006; 24: S16-22, 4. Stanley M. HPV Today 2007; 11: 1-16 No viremia Local immunosuppression No inflammation, no danger signals Uncertain whether natural HPV infection will recall memory in vaccinated women Natural HPV Infection Induces a Weak Immune Response1-4
    14. 14. 1. Parr EL et al. J Virol 1997;71(11):8109-15, 2. Nardelli-Haefliger D et al. J Natl Cancer Inst 2003;95(15):1128-37, 3. Schiller JT et al. Nat Rev Microbiol 2004;2(4):343-7, 4. Poncelet et al. ESPID, Porto, Portugal 2007; Abstract 37, session ES2, 5. Stanley M. HPV Today 2007; 11: 1-16, 6. Einstein M, Cancer Immunol Immunother 2007; 57(4):443-51. Vaccination Induces Higher Antibodies in the Blood and Site of Infection • Data show that vaccine-induced antibodies in the blood can reach to the site of infection1-3 • Higher antibody levels in the blood mean higher antibody levels at the site of infection4 • Antibodies neutralize the virus & prevent entry into cells5,6
    15. 15. GARDASIL® : The Only Quadrivalent HPV Vaccine1 • HPV types 6, 11, 16, 18 • Manufactured in Saccharomyces cerevisiae • Amorphous aluminum hydroxyphosphate sulfate (AAHS) adjuvant – 225 μg per dose • 0-, 2-, 6-month dosing regimen • Does not contain viral DNA and therefore not infectious 1. Worldwide Product Circular. GARDASIL® [Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine]; WPC-GRD-I-122008.
    16. 16. What is the BEST AGE for HPV Vaccination?
    17. 17. BEST AGE for HPV Vaccination? • Since, the best immune response is observed in the younger age groups1 the vaccine is best administered in this age group • WHO recommends vaccination at the age of 9-13 yrs 1. Harper DM. Prophylactic human papillomavirus vaccines to prevent cervical cancer: review of the Phase II and III trials. Therapy 2008 May 1;5(3):313-24
    18. 18. WHO SAGE Recommendations: Primary Target Population for Vaccination1 SAGE = Strategic Advisory Committee of Experts; WHO = World Health Organization. 1. World Health Organization. Wkly Epidemiol Rec. 2009;84:1–16. Vaccination is most effective when given to femalesVaccination is most effective when given to females nanaïïve to infection with vaccine-related HPV typesve to infection with vaccine-related HPV types Primary target population is likely to be girls 9 or 10Primary target population is likely to be girls 9 or 10 through 13 years of agethrough 13 years of age
    19. 19. 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 Age at Enrollment (Years) 500 700 900 1100 1300 1500 1600 SerumcLIAGMTWith 95%CI,mMU/mL Adolescent Females Young Adult Females Serum anti-HPV 6 responses 1 month after completion of vaccination regimen Per-protocol immunogenicity population (ages 9–26)a Higher Immune Response in Adolescents Versus Young Adults1 a Inclusive of protocols 007, 013, 015, 016 and 018; all GMTs measured using competitive Luminex® immunoassay; women 24–26 years of age were omitted in the figure because of small numbers. Similar results were observed for HPV 11, 16, and 18. GMT = geometric mean titer. 1. Giuliano AR et al. J Infect Dis. 2007;196:1153–1162.
    20. 20. Is it Worth Vaccinating Sexually Active Women?
    21. 21. Women Remain at Risk for Acquiring HPV Infection Throughout Their LifetimesCumulativeRiskofHPVInfection (%) Adapted from Muñoz N et al. J Infect Dis. 2004;190:2077-2087. Reprinted with permission from The University of Chicago Press. Copyright © 2004 by the Infectious Diseases Society of America. All rights reserved. Cohort of Colombian Women N=1610 Years 0 10 20 30 40 50 0 1 2 3 4 5 Age at Baseline (Years) 15-19 20-24 25-29 30-44 45+
    22. 22. Estimated coverage of cervical cancer screening in India, by age & study WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Human Papillomavirus and Related Cancers in India. Summary Report 2010. [Accessed on 5th July,2010]. Available at www. who. int/ hpvcentre Cervical Cancer Screening Practice in India Overall 2.6%
    23. 23. 0% 20% 40% 60% 80% 100% 16-26 Years Old 24-45 Years Old WomenVaccinatedWithGARDASIL Estimated Benefit of Vaccination With GARDASIL in Sexually Active Women 99.9% of women will benefit2 99.6% of women will benefit2 ► Women who have been exposed to at least 1 but not all vaccine- targeted HPV types will derive some benefit from vaccination.1 1. Wright TC Jr et al. Gynecol Oncol. 2008;109(2 suppl):S40-S47. 2. Data on file, MSD. Infected with all 4 types Infected with 3 types Infected with 2 types Infected with 1 typeWomen unexposed to any vaccine-targeted type
    24. 24. Long Term Protection
    25. 25. Rapid and Strong Anamnestic Response to Antigen Challenge Rapid and Strong Anamnestic Response to Antigen Challenge GMT = geometric mean titer *Similar response with the other three types of HPV within vaccine Olsson SE et al. Vaccine 2007;25:4931-4939. 5714 60 61 Time (months) 3018 24 36 540 3 6 72 12 3870 0 1000 2000 3000 4000 5000 6000 7000 Anti-HPV 16* response (GMT levels with 95% CI) n=78 Placebo n=70 108 4466 Immune challenge Immune memory Q HPV: Demonstrated Immune Memory
    26. 26. GARDASIL® : Nordic Cancer Registry Extension Evaluation of Long-Term Efficacy of Vaccination • Nordic European countries have organized mass screening programs. – Compulsory reporting of Paps, biopsies, CIN/cancer • By enrolling phase III studies in the region, we can evaluate: – Duration of effectiveness – Data for use in assessing interaction of vaccination with cervical screening programs – Long-term safety Denmark Norway Iceland Sweden CIN = cervical intraepithelial neoplasia.
    27. 27. Data on File a FUTURE= Females United to Unilaterally Reduce Endo/Ectocervical Disease Registry-Based Follow-Up Vaccination Reports 6 years 8 years 10 years US FDA Approval 5 years 7 years3 years 2003 2004 2005 2006 2007 2008 20132010 2011 20122009 3.5 years FUTUREa II Study Total Duration Time since approval Report of 6- yr F/U Follow-Up Through Nordic Registries Provides a Sentinel Cohort (Vaccinated at the Start of Study)
    28. 28. Key Objectives • Evaluate the long-term effectiveness of GARDASIL – Look for possible breakthrough disease from vaccine- related HPV types • Study possible HPV type replacement or cross- protection effects in non-vaccine HPV types • Characterize the long-term immune response both serologically and through continued effectiveness • Assess long-term safety Kjaer SK, An evaluation of the long-term effectiveness, immunogenicity and safety of the quadrivalent vaccine in previously vaccinated women, Presented at Eurogin 2011
    29. 29. 0 0 0 100 % 100 % 100 % 0 20 40 60 80 100 Zero number of cases Vaccine Effectiveness Vaccine Effectiveness Vaccine Effectiveness (N=1,080) (N=921) (N=1.032) HPV 16/18-Related CIN 2 or Worse HPV 16-Related CIN 2 or Worse HPV 18-Related CIN 2 or Worse Zero number of cases Zero number of cases Vaccine effectiveness measures the relative reduction of the disease incidence in vaccine recipients compared to the baseline incidence rate of 0.0287 per 100 person-years established from the incidence rate in an unvaccinated cohort and under the assumption vaccine efficacy is 90%. Per Protocol Efficacy Population Percentage Data on File Effectiveness Against HPV 16/18-Related CIN 2 or Worse
    30. 30. 0 0 0 0 0 0 20 40 60 80 100 Vaccineeffectiveness (N=1,080) Vaccineeffectiveness Vaccineeffectiveness Vaccineeffectiveness Vaccineeffectiveness Zero number of cases Zero number of cases Zero number of cases Zero number of cases Zero number of cases (N=1,080) (N=1,080) (N=1,080) (N=1,080) CIN 2 CIN 3 CIN 3 + AIS CC Vaccine effectiveness measures the relative reduction of the disease incidence in vaccine recipients compared to the baseline incidence rate of 0.0287 per 100 person-years established from the incidence rate in an unvaccinated cohort and under the assumption vaccine efficacy is 90%. Percentage Per Protocol Efficacy Population 100 % 100 % 100 % 100 % 100 % Data on File Effectiveness By Lesion Type
    31. 31. Safety
    32. 32. Post licensure: Health authorities reaffirm the positive safety profile of Gardasil® 1. EMEA statement on the safety of GARDASIL® . EMEA/CHMP/103339/2009. http://www.emea.eu/humandocs/PDFs/EPAR/gardasil/Gardasil_press_release.pdf - last accessed on 16.04.10. 2. Centers for Disease control website. Available at: http://www.cdc.gov/vaccinesafety/vaers/gardasil.htm- last accessed on 16.04.10. 3. RELEVE EPIDEMIOLOGIQUE HEBDOMADAIRE, No. 15, 2009, 84, http://www.who.int/wer 4. Press release Spain MINISTERIO DE SANIDAD Y POLÍTICA SOCIAL 23.04.2009
    33. 33. Genital Warts What is the importance of other HPV diseases eg. Genital Warts?
    34. 34. Australia experience
    35. 35. Standardized Incidence Ratios (SIRs) of Cancer among women diagnosed of GW in Denmark during 1978–2009 2.8 1.5 5.9 7.8 14.8 4.7 4.8 0 2 4 6 8 10 12 14 16 All HPV related cancers Cervix uteri Vagina Anus Vulva Tonsils HPV Associated StandardizedIncidenceRatios(SIRs) CI: 2.4- 3.1 CI: 5.5- 9.2 CI: 2.2-12.9 CI: 5.4- 11.0 CI: 11.7-18.6 CI: 2.3-8.4 CI: 2.7-8.0 Diagnosis of GW was strongly related to anal, vulvar, vaginal, cervical & subsites of HN cancer with confirmed HPV association. 3. Blomberg et al Genital Warts and Risk of Cancer: A Danish Study of Nearly 50 000 Patients With Genital Warts, J Infect Dis. (2012) 205 (10): 1544-1553. doi: 10.1093/infdis/jis228
    36. 36. Organizations That Have Issued Guidelines for Quadrivalent HPV Vaccine • Advisory Committee on Immunization Practices (ACIP) • American College of Obstetricians & Gynecologists (ACOG) • American Cancer Society (ACS) • American Academy of Pediatrics (AAP) • American Academy of Family Physicians (AAFP) • American College Health Association (ACHA). • World Health Organization (WHO) - Consultation on HPV vaccines • Canada (National Advisory Committee on Immunization) • Australia and New Zealand HPV Project • High Council of Public Health - France • The International Union Against Cancer (IUCC) • Canadian Pediatric Society # MMWR, March 12, 2007 / Vol. 56 , # Report of the Consultation on Human Papillomavirus Vaccines World Health Organization, Geneva, April 2005 National Advisory Committee on Immunization. # Can CommunDisRep. 2007; 33:1-32, # Guidelines for the Management of Genital HPV in Australia and New Zealand, 5th Edition -2007, # Notice regarding vaccination against human papillomavirusstrains 16 and 18 by a bivalent vaccine –14 December 2007, # www.uicc.org, # Paediatr Child Health 2007 12(7): 599 –603, # http://www.acog.org/from_home/publications/press_releases/nr08-08-06.cfm, visited on7th March 2008, CA Cancer J Clin2007;57:7–28, # PEDIATRICS Volume 120, Number 3, September 2007, #Am Physician. 2007;75(9). Available at: http://www.aafp.org/afp/20070501/practice.html. Accessed May 30, 2007. # American College Health Association (ACHA). Vaccine Preventable Diseases Committee. Recommendations for institutional prematriculation immunizations. August 2006. Available at: http://www.acha.org/info_resources/guidelines.cfm. Accessed May 16, 2007.
    37. 37. WHO Position Statement 2009 Quadrivalent HPV vaccine Bivalent HPV vaccine Licensed for Cervical Precancers & Cancers in females Yes Yes Licensed for vulvar/ vaginal Precancers & Cancers in females Yes No Licensed for anogenital warts in females Yes No Licensed for anogenital warts in males In some countries No Data available up to 5 – 6.5 yrs Yes Yes Data in HIV patients Yes Data not available Co-administration with other vaccines Can be give with other vaccines Can be give with other vaccines Partial Efficacy against HPV 31 & 45 Yes Yes Efficacy against CIN2/3 99% 90% May be given in lactating women Yes Safety data not available Weekly epidemiological record, 10 APRIL 2009, 84th YEAR, No. 15, 2009, 84, 117–132 available on http://www.who.int/wer accessed on 24th April 2009
    38. 38. FOGSI Recommendations • The HPV vaccine is a prophylactic vaccine. • Both the bivalent and quadrivalent vaccine protects against infection of HPV genotypes (HPV-16 and HPV-18) that account for about 70% of HPV-related cervical cancers. • Routine HPV vaccination is recommended for females http://www.fogsi.org/prevention_of_Cervical_Cancer.html
    39. 39. IAP Recommendations • The recommended age for initiation of HPV vaccination is 10-12 years. • As of current licensing regulations in India, catch up vaccination is permitted up to the age of 45 years. • The currently available vaccines are safe and efficacious. • The HPV vaccines are thus of public health importance IAP guidebook on immunization
    40. 40. Cervical Cancer Screening Guidelines for Average-Risk Women 2013
    41. 41. 1. American Cancer Society (ACS) 2.American Society for Colposcopy and Cervical Pathology (ASCCP), 3. American Society for Clinical Pathology (ASCP) 4. U.S. Preventive Services Task Force (USPSTF) 5. American College of Obstetricians and Gynecologists (ACOG) Endorsed by
    42. 42. FOCUS Of Cervical Cancer Screening Guidelines 2013 • When to start screening • Screening method and intervals • When to stop screening • Screening after Hysterectomy • Pelvic exams • Screening among women who have been vaccinated against human papillomavirus (HPV)
    43. 43. 2013 Guidelines for Screening of Cervical Cancer When to start Age 21 regarding of age of sexual initiation Screening methods and interval 1. Cytology (21-65 yrs) 2. 2. If HPV Co- test done a. (21 – 29 yrs) b. (30-65 yrs) 3. Primary HPV testing Every 3 years Not used if less than 30 yrs 5 yrs 30-65 yrs HPV test not recommended When to stop > 65 yrs Screening post hysterectomy Pt with total hysterectomy – Stop screening Pt. with supra – cervical hysterectomy – continue Screening in HPV Immunised Done as Routine Statement about annual screening Not to be screened annually
    44. 44. When to start screening ?
    46. 46. •Most HPV infections are transient •When HPV infection persists, transit to cancer is quite long •Spontaneous regression of low grade lesions is common •Invasive cervical cancer is very rare in 15-19 year olds -14 cervical cancers annually -1-2 cases per 1 million women •In teens, screening does not reduce mortality -Cervical cancer rates have not changed since 1973- 1977, before practice of screening at 18 or first intercourse Why Start Cervical Cytology at 21? ACOG Practice Bulletin No. 109, Dec 2009
    47. 47. Screening method and intervals 21 to 65 Years • Cytology 21-29 years of age EVERY 3 YEARS. (conventional or 30-65 years of age liquid based) Strong recommendation Second Recommendation
    48. 48. Statement about annual screening FOR SCREEN NEGATIVE If Screening Negative Repeat after 3 years Women of any age should not be screened annually by any screening method. (Strong recommendation) However , they should come for annual check-up
    49. 49. HPV co-testing SHOULD NOT BE USED for women aged <30 years. HPV Co -Test (cytology + HPV test administered together) 21-29 years of age
    50. 50. 30 – 65 years of age • If Screen Negative Every 5 years (Strong recommendation) • THIS IS THE PREFERRED METHOD • (Weak recommendation). HPV co-test (cytology + HPV test administered together)
    51. 51. Proposed Algorithm for the Management of Women ≥30 HPV Negative HPV Positive Repeat both tests at 5 years HPV 16 - / 18 – Other HR HPV + HPV 16 + and / or HPV 18 + ColposcopyRepeat both tests at 1 year Cytology Negative + HPV Testing
    52. 52. Annual cervical cancer screening should NOT be performed. (Level A evidence) Patients should be counseled that annual well-woman visits are recommended even if cervical cancer screening is not performed at each visit. HPV Co- Test Screen Negative in women aged 30–65 years
    53. 53. Primary HPV testing (alone) For Screening screening by HPV testing alone is not recommended in most clinical settings. (Weak recommendation)
    54. 54. When to Stop Screening • Stop at age 65 for women with adequate negative prior screening, no CIN2+ within the last 20y. Definition of adequate negative screening: • 3 consecutive negative Paps or • 2 consecutive negative HPV tests
    55. 55. Rationale for stopping at 65 years • CIN2+ is rare after age 65 – Most abnormal screens, even HPV+, are false + and do not reflect precancer • HPV risk remains 5-10% • Incident HPV infection unlikely to lead to cancer within remaining lifetime Chen HC et al. JNCI 2011;103:1387-96; Rodrigues AC et al. JNCI 2009;101:721-8
    56. 56. When NOT to stop at age 65 years If history of CIN2, CIN3, or AIS – Continue “routine screening” for at least 20 years, “even if this extends screening past age 65.”
    57. 57. When to stop screening - 2 • Stop after HYSTERECTOMY with removal of cervix and no history of CIN2+ • “Evidence of adequate negative prior screening is not required”
    58. 58. Rationale for stopping after Hysterectomy • Vag cancer rate is 7/million/year • 663 vag cuff Paps needed to find one VAIN • 2,066 women followed after hyst. for average 89 months – 3% had VAIN, 0 had cancer • Risk of Pap abnormality after hyst = 1%. Pearce KF et al. NEJM 1996;335:1559-62; Piscitelli JT et al. AJOG 1995;173:424-30
    59. 59. Women who have had a SUPRA-CERVICAL HYSTERECTOMY (cervix intact) should continue screening according to Age guidelines. (Strong recommendation) SCREENING IN POST – HYSTERECTOMY CASE
    60. 60. Women at any age with a history of HPV Vaccination should be screened according to the age specific recommendations for the general population. Screening among those immunized against HPV 16/18 5th Recommendation
    61. 61. SCREENING A VACCINATED COHORT • Vaccination against HPV 16/18 – Reduces CIN3+ by 17-33% – Reduces colposcopy by 10% – Reduces treatment by 25% • “ Recommended screening practices should not change on the basis of HPV vaccination.” Paavonen J et al. Lancet 2009;374:301-14
    62. 62. The need for a BIMANUAL PELVIC EXAM in subsequent yearly check-ups <21 – No need 21 - shared decision
    63. 63. Let’s Recap 2013 Guidelines
    64. 64. AGE SCREENING < 21 No Screening 21-29 Cytology alone every 3 years 30-65 Acceptable: Cytology alone every 3 years* Preferred ??: Cytology + HPV every 5 years* OR > 65 No screening, following 3 consequetive neg prior screens in last decade After total hysterectomy No screening, if no history of CIN2+ in the past 20 years of cervical cancer ever HIV-positive -Immunosuppressed (e.g., Annually 2013 Guidelines : ACS, ASCCP, American Society for Clinical Pathology CA Cancer J CLIN March 2012 • 1st time that all 3 organizations involved with cervical cancer prevention and the USPSTF have endorsed equivalent guidelines
    65. 65. Management of Abnormal PAP smear (According to ASSCO Guidelines) 20 yrs and younger 21 years and older and pre – menopausal; Post – menopausal; (any age) Pregnant ASC-US Repeat Pap test in 12 months HPV test or repeat Pap test in 6 months and 12 months or colposcopy HPV test or repeat pap test in 6 months or 12 months or colposcopy In women 20 yrs and younger repeat pap test in 12 months . in women 21 yrs and older HPV test or colposcopy (without endocervical sampling) LSIL Repeat pap test in 12 months Colposcopy HPV test or repeat pap test in 6 months and 12 months or colposcopy In women 20 years and younger repeat pap test in 12 months in women 21 years and older : colposcopy (without endocervical sampling) or further testing may be delayed until after birth
    66. 66. Management of Abnormal PAP smear (According to ASSCO Guidelines) HSIL Colposcopy Colposcopy or LEEP Colposcopy or LEEP Colposcopy without endocervical sampling ASC – H Colposcopy (but without endocervical sampling in pregnant women) AGC – all Subcategories Except atypical endometrial cells Colposcopy with endocervical sampling and HPV testing and endometrial sampling (if older than 35 years or risk of endometrial neoplasia) Colposcopy and HPV testing (without endocervical or endometrial sampling) AGC- atypical endometrial cells Endometrial and endocervical sampling followed by colposcopy and HPV testing Colposcopy and HPV testing (without endocervical or endometrial sampling
    67. 67. How to prepare for your pap test - Not to schedule during periods. - If you are going to have a pap testing in the next two days • You should not douche (rinse the vagina with water or another fluid). • You should not use a tampon • You should not use a birth control foam, cream or jelly • You should not use a medicine or cream in your vagina
    68. 68. Summary 1. 27% of the world burden of Cervical Cancer is seen in India. 2. Screening is recommended in women of >21yrs 2013 3. No screening required before 21 yrs 4. Screening should stop at 65 yrs and after hysterectomy “The biggest gain in reducing cervical cancer incidence and mortality would be achieved by increasing screening rates among women rarely or never screened. . . Clinicians, hospitals, health planners, and public health officials should promote HPV vaccination and screen women between 21 – 65 yrs .” ACS, 20002
    69. 69. Every Wednesday of The Month F R E E
    70. 70. Thank You Say No to Cervical Cancer