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Hpv and cancers-DR.DIVYA JAIN


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Hpv and cancers-DR.DIVYA JAIN

  3. 3. HUMAN PAPILLOMA VIRUS • Papovaviridae family • small DNA-containing virus • double-stranded circular DNA of 7900 base-pairs long • Non-enveloped virus • Epitheliotropic (infects epithelial cells) • Infects only humans.
  4. 4. CLINICAL TYPES • High Risk Types: Found preferentially in precancerous and cancerous specimens including HPV 16,18,31,33, 34,35,39,45,51,52,56,58,59,66,68,70 • Low Risk Types: Detected in wart and non-malignant lesion including HPV 6,11,42,43,44
  5. 5. HPV TRANSMISSION • Direct skin-to-skin contact • Usually, but not always sexual contact • Infected birth canal • Fomites (very rare)
  6. 6. RISK FACTORS • Multiple partners • Early age at first intercourse (16 years or younger) • Male partner has (or has had) multiple sex partners • Smoking: 4 times R.R. • Immunosuppression: HIV, Rheumatoid Arthritis, Cancer • Condoms: not very good at preventing HPV • Spermide nonoxynol-9: not protective
  7. 7. HPV INFECTIONS: SUMMARY • Most people are infected by HPV at some time • Immune system usually clears HPV, but not always • Persistent low-risk HPV can lead to warts • Persistent high-risk HPV can lead to pre-cancer • Long peristence of HPV can lead to cancer. HPV
  8. 8. MOLECULAR VIROLOGY • The E4 protein play a role in G2 arrest in HPV-infected cells • The 3 HPV oncogenes E5, E6, and E7 promote unrestrained cellular proliferation to allow for viral amplification but also contribute to the initiation and progression of cancer
  10. 10. Detection of Human Papilloma Virus Evidence of functioning Oncoprotein E7 •DNA In-Situ Hybridization •PCR assay for viral copies •mRNA of E6, E7 •p16 Immunohistochemistry Presence of HPV DNA
  11. 11. BY 2020…. • The annual number of HPV-positive OPSCCs (approximately 8,700 patients) will surpass the annual number of cervical cancers (approximately 7,700 patients) with the majority occurring among men (approximately 7,400). • By 2030, OPSCC will likely constitute a majority (47%) of all H & N cancers. Chaturvedi A K et al. JCO 2011
  12. 12. HEAD AND NECK CANCER • 6th most common cancer worldwide • More than 600,000 new diagnoses annually • > 95% are Squamous cell Carcinomas • In recent years, many studies have shown that some 25% of Oropharyngeal carcinomas are associated with Oncogenic or high-risk HPV, already widely implicated in cervical carcinoma
  13. 13. COMMONEST SITE OF INFECTION IN HEAD AND NECK • The commonest head and neck sites associated with HPV infection are • Tonsil, • Base of tongue, • Lingual tonsil • Lateral wall of the oropharynx.
  14. 14. • Patients with potentially HPV related SCCs often do not have the known risk factors, like smoking, alcohol consumption or tobacco chewing. • Research has shown an association between the HPV related cancers and having a higher number of sexual partners and an increase in oral sexual behaviour. • Pts present with a similar signs and symptoms as other cancer due to other causes.
  15. 15. DISEASE COURSE AND PROGNOSIS.. • On the assumption that HPV-associated H&N cancer is an entity of its own, clinical studies have increasingly been published… • These studies show that patients with HPV-positive cancers have a much better prognosis.
  16. 16. •Why does HPV positive oropharyngeal cancer have a better prognosis?
  18. 18. MANAGEMENT • The standard treatment for oropharyngeal Squamous cell cancer at present is mainly dependent on the stage of the disease and patient and clinician preferences. • Single-modality treatment, in the form of surgery or radiotherapy, is usually recommended for early (T1- T2, N0) disease.
  20. 20. HPV-positive Oro pharyngeal Carcinoma has better prognosis Better Survival Long-term morbidity associated with current treatment will be longer lasting De-escalating Treatment Regimens
  21. 21. DEINTENSIFICATION • Deintensification trials can be done in 2 ways: 1. Deintensification of local therapy via using alternative chemotherapy, reduced dose radiation or surgery 2. Use of induction therapy to identify good-responding patients for subsequent dose reduction.
  22. 22. FUTURE • HPV detection would become a standard prognostication factor for H & N cancers like ER-PR & PSA. • We may use significantly different treatments for patients with HPV-positive as compared with HPV-negative HNC.
  24. 24. • 2nd most common cancer in women worldwide • Most common cause of death in females in developing countries • In India,every year 72,000 females die of cervical cancer
  25. 25. Professor Harald Zur Hausen Prince Mahidol Award 2005 Nobel Prize 2008 The First one who demonstrated HPV-DNA sequences in cervical cancer biopsies and cervical cancer cell lines.
  26. 26. Natural History of HPV & Cervical Cancer Normal Cervix HPV Infection Pre-cancer Cancer Infection Progression Invasion RegressionClearance  Persistence
  27. 27. CIN: PRE-CANCEROUS WARNING • Cervical intraepithelial neoplasia (CIN) observed in disease progression • New, abnormal, disorganized growth of cervix epithelium
  28. 28. STAGES OF CIN 1. CIN I • Number & depth of abnormal cells is low 2. CIN II • Abnormal cell growth penetrates about ½ the thickness of cervical epithelium 3. CIN III • “carcinoma in-situ” • Abnormal cell growth penetrates entire thickness of cervical epithelium 4. Invasive Cervical Cancer • Abnormal cell growth penetrates beyond cervical epithelium
  29. 29. STAGES OF CIN: HISTOLOGY NORMAL CIN I CIN II CIN III Furumoto et al., 2002.
  30. 30. CERVICAL CANCER COFACTORS • HPV is NOT sufficient cause for cervical cancer • Combination of HPV & 1 or more cofactors increase risk of cancer progression • HYGIENE • PARITY • HORMONAL CONTRACEPTIVES • SMOKING
  31. 31. PREVENTION BETTER THAN CURE • PRIMARY PREVENTION-Vaccination against HPV • SECONDARY PREVENTION-Screening for precancerous changes (and treatment if problems found)
  32. 32. HISTORY OF THE CONVENTIONAL PAP SMEAR • Developed by Dr. George N. Papanicolaou in 1940’s • Most common cancer screening test • Key part of annual gynecologic examination • Has greatly reduced cervical cancer mortality .
  33. 33. CERVICAL CANCER SCREENING GUIDELINES • First screen 3 years after first intercourse or by age 21 • Screen annually with regular Paps or every 3 years with liquid-based tests • After three normal tests, can go to every 5 years • Stop at 65-70 years with history of negative tests • Still need annual check-ups Cervical Cytology Screening. ACOG Practice Bulletin No. 45. 2016; 102:417-27.
  34. 34. HPV VACCINE
  36. 36. VACCINE MOA • Both the vaccine provide protection against HPV 16 & HPV 18. • They make use of virus-like particles composed of the major capsid protein L1 of the targeted HPV subtypes.
  37. 37.  GARDASIL® should be administered intramuscularly as 3 separate 0.5-mL doses according to the schedule of 0,2,6 month for females aged 9 through 26 years.  Care must be taken not to inject intravenously as it can lead to syncopal attack.  Efficacy is of 5 to 10 yrs.  No booster dose has been recommended. DOSAGE
  38. 38. Indian and United States Organizations IAP – Indian Academy of Pediatrics FOFSI - The Federation of Obstetric & Gynaecological Societies of India AAP = American Academy of Pediatrics ACHA = American College Health Association ACOG = American College of Obstetricians and Gynecologists AAFP = American Academy of Physicians SAM = Society for Adolescent Medicine Recommendations IAP FOGSI ACOG AAFP SAM ACHA AAP Routine vaccination in females 11-12 years old & catch-up vaccination in 13-26 year olds √ √ √ √ √ √ √ Females 9-10 years old may be vaccinated √ √ √ √ √ √ √ Vaccinate regardless of previous HPV infection or abnormal Pap test results √ √ √ √ √ √ √ Continue Pap testing after vaccination √ √ √ √ √ √ √ Recommendations by US based organizations are only for Gardsil as it is the only USFDA approved HPV vaccine 1. http://www.acog.org/from_home/publications/press_releases/nr08-08-06.cfm, visited on7th March 2008 2. American Academy of Family Physicians. Practice guidelines: ACIP releases recommendations on quadrivalent human papillomavirus vaccine. Am Fam Physician. 2007;75(9). Available at: http://www.aafp.org/afp/20070501/practice.html. Accessed May 30, 2007. 3. Society for Adolescent Medicine. Human papillomavirus (HPV) vaccine: a position statement of the Society for Adolescent Medicine. Available at: http://www.adolescenthea lth.org/positionstatement_HPV_vaccine.pdf. Accessed May 16, 2007. 4. 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. 5. PEDIATRICS Volume 120, Number 3, September 2007 6. INDIAN PEDIATRICS: VOLUME 45--AUGUST 17, 2008 7. The Federation of Obstetric & Gynaecological Societies of India (FOGSI). Recommendations for Vaccination against Human Papilloma Virus (HPV) Infection For the prevention of Cervical Cancer. Available at http://www.fogsi.org/hiv_vaccine.html. accessed on 20th Feb 20009
  39. 39. HPV VACCINE – IN H&N CANCER??? • HPV-16 is responsible for only 50-60% of cervical cancers • In HPV + oropharyngeal cancer, HPV-16 subtype is present in 94% of these cancers • Theoretically, HPV vaccine should be even more effective in head and neck cancer . • No clinical data available for humans.
  40. 40. • Should boys be vaccinated? • Can vaccine be given to pregnant women /lactating mother? • Can vaccine be given after development of cancer?
  41. 41. THANK YOU…..