HUMAN PAPILLOMA VIRUS Updates and Vaccination       Dr.T.V.Rao MD
Human PapillomavirusHuman papillomavirus (HPV ) is a member of thepapillomavirus family of viruses that is capable ofinfec...
Nobel Prize for DiscoveriesThe Nobel Assembly at Karolinska Institutet hasawarded the Nobel Prize in Physiology or Medicin...
Harald zur Hausen awarded Nobel prize
Sexual Contact mainly spread the                InfectionMore than 30 to 40 types of HPV are typicallytransmitted through ...
Immuno suppression and HPVImmunosuppressedpatients experience anincreased incidence ofwarts and cancer ofcervixAll HPV ass...
Pathology and PathogenesisTransmission occurs byclose contact,Viral particles arereleased from surfaceof paillomatous lesi...
Clinical Importance ManifestationsGlobally more than 660 million people are infected with Genitalhuman papillomas infectio...
HPV 16 and 18 are High risk factorsHPV types 6 and 11 are typically labeled as lowrisk because infection with these types ...
The percentages of cancers caused by        oncogenic HPV are as ….Cervical cancer100%Anal cancer - 90%Vulvar cancer - 40%...
The Incidence Differs in Developing WorldIn many lesser-developedcountries, cervical cancer isthe most common canceramong ...
Can Cause Cancers Several Types of            CancersHPV infections canpersist for many years.Persistent infectionswith hi...
What is the association between HPV        infection and cancer?                     Persistent HPV infections            ...
Multiple Sex Partners a Risk FactorHaving many sexualpartners is a risk factor forHPV infection.Nevertheless, most HPVinfe...
Human Papilloma VirusSexually Transmitted Virus which can lead to         cervical dysplasia (cancer). Found in 99.7%   of...
Human Papilloma Virus80% of the sexually active adult population will contract HPV                   U.S. spent over $1.6 ...
Sexually ActiveWe define the sexually   active population     age range as:          The range in years in which an indivi...
Sexually Active Ages    Given this concept of sexual activity the age ranges for    each model are:                       ...
Risk of TransmissionThe risk of transmission is based on two factors:   The risk of     transmission in one     sexual enc...
Pathophysiology of HPV InfectionLaboratory research has indicatedthat HPVs produce proteins knownas E5, E6, and E7. These ...
Relative Risk of TransmissionHPV :   Male-to-Female 80%   Female-to-Male 70%
How are HPV infections detected?Cervical cells can be tested to identify high-risk types ofHPV that may be present. HPV DN...
FDA Approves Vaccine for HPVThe U.S. Food and Drug Administration (FDA) has approved twovaccines to prevent HPV infection:...
Two Vaccines are Licensed for Human                Use                   Both Gardasil and Cervarix                   are ...
Gardasil vaccineThe Gardasil vaccine, which isproduced by Merck & Co., Inc.(Merck), is called a quadrivalentvaccine becaus...
Cervarix Vaccine         Cervarix is produced by         GlaxoSmithKline (GSK). It is         called a bivalent vaccine   ...
The Vaccines are Effective in Targeted             HPV types                  Gardasil and Cervarix are highly            ...
HPV is Totally Not Protective ?Neither of these HPVvaccines has been proven toprovide completeprotection againstpersistent...
Vaccine is Not Totally Protective on all            types of HPV                     Overall, therefore, about 30         ...
A Regular Check up for Detection of Cancer   Cervix essential even in ImmunizedBecause the vaccines donot protect against ...
How long do the vaccines protect             against infection?The duration of immunity is notyet known. Research is being...
Will booster vaccinations be needed?                   Studies are under way                   to determine whether       ...
Who should get these vaccines?Both Gardasil and Cervarix areproven to be effective only ifgiven before infection with HPV,...
Vaccination in Males           Data from Merck show           high efficacy of Gardasil in           males for preventing ...
HPV  Total Sexually Active PopulationSusceptible               Vaccinated                          VaccinatedInfectious   ...
Concerns on HPV Vaccination              Reports of adverse events after              administration of the human         ...
HPV safety is EvaluatedGardasil is 1 of the "most heavilystudied and intensively monitoredvaccines," commented JohnIskande...
Adverse-Event Reports on Watchdog            Web SitesThe actual reports collected byVAERS have been madeavailable on the ...
PAP Smear is Still Important for timely     Diagnosis of Caner Cervix                     Regardless of                   ...
Is there a Totally Safe and Highly          Effective VaccineThe question remainsunanswered as there is noVaccine which is...
Follow me for more articles of interest on issues on               Infectious diseases   Dr.T.V.Rao MD                    ...
The Programme is Created by Dr.T.V.Rao MD for ‘ e’ Learning resourcesfor Medical and Paramedical Professionals            ...
Human Pailloma Virus Updates and Vaccination
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Human Pailloma Virus Updates and Vaccination

  1. 1. HUMAN PAPILLOMA VIRUS Updates and Vaccination Dr.T.V.Rao MD
  2. 2. Human PapillomavirusHuman papillomavirus (HPV ) is a member of thepapillomavirus family of viruses that is capable ofinfecting humans. Like all papillomaviruses, HPVsestablish productive infections only in the stratifiedepithelium of the skin or mucous membranes. While themajority of the nearly 200 known types of HPV cause nosymptoms in most people, some types can cause warts(verrucae), while others can – in a minority of cases –lead to cancers of the cervix, vulva, vagina, and anus inwomen or cancers of the anus and penis in men.
  3. 3. Nobel Prize for DiscoveriesThe Nobel Assembly at Karolinska Institutet hasawarded the Nobel Prize in Physiology or Medicine2008 to Harald zur Hausen, Françoise Barré-Sinoussiand Luc Montagnier for their discoveries of two virusescausing severe human diseases.One half is awarded to Harald zur Hausen "for hisdiscovery of human papilloma viruses causingcervical cancer" and the other half jointly toFrançoise Barré-Sinoussi and Luc Montagnier "for theirdiscovery of human immunodeficiency virus"
  4. 4. Harald zur Hausen awarded Nobel prize
  5. 5. Sexual Contact mainly spread the InfectionMore than 30 to 40 types of HPV are typicallytransmitted through sexual contact and infect theanogenital region. Some sexually transmittedHPV types may cause genital warts. Persistentinfection with "high-risk" HPV types—differentfrom the ones that cause skin warts—mayprogress to precancerous lesions and invasivecancer. HPV infection is a cause of nearly all casesof cervical cancer however, most infections withthese types do not cause disease.
  6. 6. Immuno suppression and HPVImmunosuppressedpatients experience anincreased incidence ofwarts and cancer ofcervixAll HPV associatedinfections occur in HIV/ AIDS morefrequently
  7. 7. Pathology and PathogenesisTransmission occurs byclose contact,Viral particles arereleased from surfaceof paillomatous lesionsCauses infections atcutaneous andmucosal sites.
  8. 8. Clinical Importance ManifestationsGlobally more than 660 million people are infected with Genitalhuman papillomas infections.Most common infection of the Genital tract.6-2 million new infections occur in USA.Most common in youth < 25 yearsHPV infections are accepted as the cause of anogenital cancers.Majority ( 99 % ) are linked to HPV type 16HPV 18 type is found in Cervical carcinomasHPV 16 and 18 are identified in > 70 % of cervical carcinomasHe la cells widely used in laboratories are associated withinfection with HPV 18 DNA
  9. 9. HPV 16 and 18 are High risk factorsHPV types 6 and 11 are typically labeled as lowrisk because infection with these types has lowoncogenic potential and usually results in theformation of condylomata and low-gradeprecancerous lesions. HPV types 16 and 18have emerged as the high-risk types ofHPV because they are responsible for mosthigh-grade intraepithelial lesions that mayprogress to carcinomas, particularly those in theanogenital and/or mucosal category.
  10. 10. The percentages of cancers caused by oncogenic HPV are as ….Cervical cancer100%Anal cancer - 90%Vulvar cancer - 40%Vaginal cancer - 40%Oropharyngealcancer - 12%Oral cancer – 3%
  11. 11. The Incidence Differs in Developing WorldIn many lesser-developedcountries, cervical cancer isthe most common canceramong women because ofthe lack of effectivescreening programs thatmonitor cervical cytologyby Pap smear. However, a singleround of HPV screening hasbeen demonstrated to be farsuperior to conventionalcytology in reducing theincidence of cervical cancermorbidity and mortality.
  12. 12. Can Cause Cancers Several Types of CancersHPV infections canpersist for many years.Persistent infectionswith high-risk HPVs arethe primary cause ofcervical cancer. HPVinfections also causesome cancers of theanus, vulva, vagina,penis, and oropharynx
  13. 13. What is the association between HPV infection and cancer? Persistent HPV infections are now recognized as the cause of essentially all cervical cancers. It was estimated that, in 2010, about 12,000 women in the United States would be diagnosed with this type of cancer and more than 4,000 would die from it. Cervical cancer is diagnosed in nearly half a million women each year worldwide, claiming a quarter of a million lives annually.
  14. 14. Multiple Sex Partners a Risk FactorHaving many sexualpartners is a risk factor forHPV infection.Nevertheless, most HPVinfections go away on theirown without causing anytype of abnormality.However, even among womenwho develop abnormal cervicalcell changes because ofpersistent infection with high-risk HPV types, the chances ofdeveloping cervical cancer aresmall, even if the abnormal cellsare not treated.
  15. 15. Human Papilloma VirusSexually Transmitted Virus which can lead to cervical dysplasia (cancer). Found in 99.7% of all cervical cancers Types {16,18,31,45} account for 75% of cervical cancer
  16. 16. Human Papilloma Virus80% of the sexually active adult population will contract HPV U.S. spent over $1.6 billion in treating symptoms of HPV U.S. estimates2004 13,000 cases of cervical cancer 2005 $5-6 billion spent on screening tests such More than 5,000 will die as pap smears. from cervical cancer
  17. 17. Sexually ActiveWe define the sexually active population age range as: The range in years in which an individual changes sexual partners more than once per year on average
  18. 18. Sexually Active Ages Given this concept of sexual activity the age ranges for each model are: HPV 15-30 15 300 20 40 Age (years)
  19. 19. Risk of TransmissionThe risk of transmission is based on two factors: The risk of transmission in one sexual encounter The average number of sexual encounters with one partner
  20. 20. Pathophysiology of HPV InfectionLaboratory research has indicatedthat HPVs produce proteins knownas E5, E6, and E7. These proteinsinterfere with the cell functionsthat normally prevent excessivegrowth. For example, HPV E6interferes with the human proteinp53, which acts to keep tumorsfrom growing. A betterunderstanding of how theseproteins interact may helpresearchers develop ways tointerrupt the process by which HPVinfection can lead to the growth ofabnormal cells
  21. 21. Relative Risk of TransmissionHPV : Male-to-Female 80% Female-to-Male 70%
  22. 22. How are HPV infections detected?Cervical cells can be tested to identify high-risk types ofHPV that may be present. HPV DNA tests look for viralDNA from multiple high-risk HPV types and can detectthe presence of a viral infection before any cellabnormalities become visible. The FDA has approvedHPV DNA tests for follow-up testing of women withequivocal cell abnormalities on a Pap test (a screeningtest to detect cervical cell changes). HPV DNA tests arealso approved for general cervical cancer screening ofwomen over the age of 30 when done together with aPap test. There are currently no approved tests todetect HPV infections in men.
  23. 23. FDA Approves Vaccine for HPVThe U.S. Food and Drug Administration (FDA) has approved twovaccines to prevent HPV infection: Gardasil® and Cervarix®. Bothvaccines are highly effective in preventing persistent infectionswith HPV types 16 and 18, two high-risk HPVs that cause most(70 percent) cervical cancers. Gardasil also prevents infectionwith HPV types 6 and 11, which cause virtually all (90 percent)genital warts . In addition, there is some initial evidence thatCervarix provides partial protection against a few other HPVtypes that can cause cancer, but further evaluation is requiredbefore the magnitude and impact of this effect is understood.
  24. 24. Two Vaccines are Licensed for Human Use Both Gardasil and Cervarix are based on technology developed in part by National Cancer Institute (NCI) scientists. NCI, a component of the National Institutes of Health, licensed the technology to two pharmaceutical companies—Merck and GSK—to develop HPV vaccines for widespread distribution.
  25. 25. Gardasil vaccineThe Gardasil vaccine, which isproduced by Merck & Co., Inc.(Merck), is called a quadrivalentvaccine because it protects againstfour HPV types: 6, 11, 16, and 18.Gardasil is given through a series ofthree injections into muscle tissueover a 6-month period. The FDA hasapproved Gardasil for use in femalesfor the prevention of cervical cancer,and some vulvar and vaginal cancers,caused by HPV types 16 and 18 andfor use in males and females for theprevention of genital warts caused byHPV types 6 and 11. The vaccine isapproved for these uses in femalesand males ages 9 to 26 .
  26. 26. Cervarix Vaccine Cervarix is produced by GlaxoSmithKline (GSK). It is called a bivalent vaccine because it targets two HPV types: 16 and 18. This vaccine is also given in three doses over a 6-month period. The FDA has approved Cervarix for use in females ages 10 to 25 for the prevention of cervical cancer caused by HPV types 16 and 18.
  27. 27. The Vaccines are Effective in Targeted HPV types Gardasil and Cervarix are highly effective in preventing infection with the types of HPV they target. Studies have shown that both Gardasil and Cervarix prevent nearly 100 percent of the precancerous cervical cell changes caused by the types of HPV targeted by the vaccine for up to 4 years after vaccination among women who were not infected at the time of vaccination
  28. 28. HPV is Totally Not Protective ?Neither of these HPVvaccines has been proven toprovide completeprotection againstpersistent infection withother HPV types, althoughsome initial results suggestthat both vaccines mightprovide partial protectionagainst a few additionalHPV types that can causecervical cancer.
  29. 29. Vaccine is Not Totally Protective on all types of HPV Overall, therefore, about 30 percent of cervical cancers will not be prevented by these vaccines. Also, in the case of Gardasil, 10 percent of genital warts will not be prevented by the vaccine. Neither vaccine prevents other sexually transmitted diseases, and they do not treat HPV infection or cervical cancer.
  30. 30. A Regular Check up for Detection of Cancer Cervix essential even in ImmunizedBecause the vaccines donot protect against allHPV infections thatcause cervical cancer, itis important forvaccinated women tocontinue to undergocervical cancerscreening asrecommended forwomen who have notbeen vaccinated.
  31. 31. How long do the vaccines protect against infection?The duration of immunity is notyet known. Research is beingconducted to find out how longprotection will last. Phase IIIclinical trials have shown thatGardasil and Cervarix can provideprotection against HPV16 for 4years. Smaller studies havesuggested that protection is likelyto last for longer than 4 years, butit is not known if protectionconferred through vaccination willbe lifelong
  32. 32. Will booster vaccinations be needed? Studies are under way to determine whether booster vaccinations (supplementary doses of a vaccine, usually smaller than the initial dose or doses, that are given to maintain immunity) are necessary.
  33. 33. Who should get these vaccines?Both Gardasil and Cervarix areproven to be effective only ifgiven before infection with HPV,so it is recommended that they begiven before an individual issexually active. The FDAslicensing decision includesinformation about the age andsex for recipients of the vaccine.The FDA approved Gardasil foruse in females ages 9 to 26 andapproved Cervarix for use infemales ages 10 to 25.
  34. 34. Vaccination in Males Data from Merck show high efficacy of Gardasil in males for preventing genital warts associated with HPV6 and HPV11, the two HPV types that cause most genital warts. The FDA approved Gardasil for use in males ages 9 to 26 to prevent genital warts caused by HPV6 and HPV11.
  35. 35. HPV Total Sexually Active PopulationSusceptible Vaccinated VaccinatedInfectious Infectious Note: A constant population is maintained. Every year/update in Recovered the model a proportion of the population  Enters or ages-in as susceptibles  Leaves or ages-out
  36. 36. Concerns on HPV Vaccination Reports of adverse events after administration of the human papillomavirus (HPV) vaccine (Gardasil, Merck) have been making headlines, and questions over the safety of the vaccine have been raised by consumers, parents, healthcare professionals, and others, notes a recent joint statement from the US Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA). But having analyzed the available data, the agencies offer reassurance.
  37. 37. HPV safety is EvaluatedGardasil is 1 of the "most heavilystudied and intensively monitoredvaccines," commented JohnIskander, MD, actingdirector of theImmunization Safety Officeat the CDC in Atlanta,Georgia. So far the availabledata suggest that it is safe, hesaid in an interview, although headded that "there are no medicalproducts, including vaccines, thatare completely safe andeffective."
  38. 38. Adverse-Event Reports on Watchdog Web SitesThe actual reports collected byVAERS have been madeavailable on the Web site of thewatchdog organization JudicialWatch, which obtained therecords from the FDA under theFreedom of Information Act. Acompact disc containing 8864records was sent by the FDA onJune 10, 2008.
  39. 39. PAP Smear is Still Important for timely Diagnosis of Caner Cervix Regardless of whether a woman chooses to be vaccinated or not, the take-home message is to start and continue Pap screening throughout your life," Dr. Harper
  40. 40. Is there a Totally Safe and Highly Effective VaccineThe question remainsunanswered as there is noVaccine which is totallysafe and Highly effectiveto prevent or cure aDiseases. The facts shouldbe learnt with continuousobservation and wellcommunicated Knowledgethrough various peerreviewed Information
  41. 41. Follow me for more articles of interest on issues on Infectious diseases Dr.T.V.Rao MD 42
  42. 42. The Programme is Created by Dr.T.V.Rao MD for ‘ e’ Learning resourcesfor Medical and Paramedical Professionals Email doctortvrao@gmail.com

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