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Hpv
- Human papillomavirus (HPV) is a non-enveloped double-stranded DNA virus that can cause various cancers and genital warts. There are over 100 HPV types, with high-risk HPV 16 and 18 causing most cervical and other cancers. - The HPV vaccines Gardasil (HPV4) and Cervarix (HPV2) protect against HPV 16 and 18 and can prevent cancers caused by these high-risk types if administered before exposure. Vaccination is recommended for girls and boys at age 11-12. - HPV positive oropharyngeal cancer makes up the majority of oropharyngeal cancers and is associated with improved survival compared to HPV negative orophary
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Hpv
- 1.
- 2. • Non-enveloped double-strandedcircular DNA viruses with a genome of approximately 8000 kilo base pair • Viral family Papillomaviridae
- 3. Human Papillomavirus • Morethan 100 types – More than 60 cutaneous types • Can lead to skin warts – 40 mucosal types • high risk types (particularly 16 and 18) – cervical cell abnormalities – certain anogenital cancers • Low risk types (particularly 6 and 11) – cervical cell abnormalities- usually resolve spontaneously and do not lead to cancer – genital warts – respiratory papillomatosis
- 4. Cancers caused byHPV • Cervix 100% • Anal 95% • Oropharynx 70% • Vaginal 65% • Vulva 50% • Penis 5% In the US , 3% of all cancers in women and 2% of all cancers in men
- 5. Estimated average annual percentageand estimated number of cancers attributable to human papillomavirus (HPV),* by anatomic site and sex — United States, 2008–2012 MMWR Weekly / July 8, 2016 / 65(26);661– 666
- 6.
- 7. Natural History ofHPV Infection Within 1 Year 1-5 Years Up to Decades Initial HPV Infection Persistent Infection CIN 2/3 Cervical Cancer CIN 1 Cleared HPV Infection
- 8. HPV-associated Conditions HPV 16,18 Cervical cancer High/low grade cervical abnormalities Anal, Vulvar, Vaginal, Penile Head and neck cancers HPV 6, 11 Low grade cervical abnormalities Genital warts RRP Estimated % 70% 30%-50% 10% 10% 90% 90%
- 9. • Specific tropismfor keratinocytes, full productive cycle only in squamous cells • Hpv genome devided into two regions– early region and late region
- 10. 10 Gene Function L1 Majorcapsid protein, basis for peventive VLP vaccine L2 Minor capsid protein E1 Intiate viral dna replication, helicase and ATPase activity E2 Transcriptional regulatory protein E4 Late protein, disrupts cytokeratin E5 Membrane transforming protein, interacts with specific growth factor receptor E6 Transformation, targets degradation of P53, activate telomerase E7 Transformation, inactivates pRB and RB related proteins, activate centrosome duplication
- 11. Human Papillomavirus Vaccines •HPV4 (Gardasil) – contains types 16 and 18 (high risk) and types 6 and 11 (low risk) • HPV2 (Cervarix) – contains types 16 and 18 (high risk) • Both vaccines are supplied as a liquid in a single dose vial or syringe • Neither vaccine contains an antibiotic or a preservative
- 12. Human Papillomavirus Vaccines •HPV4 vaccine is approved for – females 9 through 26 years of age for the prevention of cervical cancers, precancers and genital warts – males 9 through 26 years of age for the prevention of genital warts • HPV2 vaccine is approved for – females 10 through 25 years of age for the prevention of cervical cancers and precancers – not approved for males or for the prevention of genital warts
- 13. HPV Vaccine Scheduleand Intervals • HPV4- 0, 2, 6 months • HPV2- 0, 1, 6 months • If the interval between doses is longer than recommended continue the series where it was interrupted
- 14. Correct and consistentcondom use may have a protective effect on HPV acquisition, reduce the risk for HPV-associated diseases, and mitigate the adverse consequences of infection with HPV. This statement is required by section 317 of the Public Health Service Act, 42 U.S.C., 243
- 15. HPV Vaccine Recommendations •Recommended age for routine HPV vaccination is 11 or 12 years • Vaccination is recommended for females 13 through 26 years of age not previously vaccinated or who have not completed the full 3-dose series • The 3 dose series of HPV4 may be administered to males 9 through 26 years of age to reduce their likelihood of acquiring genital warts
- 16. HPV Vaccine Contraindicationsand Precautions • Severe allergic reaction to a vaccine component or following a prior dose – yeast (HPV4) – latex (HPV2 prefilled syringe) • Moderate or severe acute illness
- 17. HPV Vaccine AdverseReactions • Local reaction 20% - 90% (pain, redness, swelling) • Temperature 100°F 10% - 13% or higher • Serious adverse events None
- 19. Preparing for aPap Smear • Schedule a day when you won’t be having your period • Do not douche 48 hours before the test • Avoid sexual intercourse 48 hours before the test • Do not use tampons, vaginal creams, foams, films or other jellies for 48 hours before the test
- 20. 20 Pap Smears 2001 BethesdaSystem • Specimen type – Coventional vs Liquid sample • Specimen adequacy – Satisfactory or unsatisfactory for evaluation • General categorization – Negative for Intraepithelial lesion/malignancy – Epithelial cell abnormality (squamous or glandluar) – Other things observed (ex. Endometrial cells)
- 21. 21 Pap Smears 2001 BethesdaSystem • Epithelial cell abnormalities – Squamous • Atypical squamous cell of undetermined significance(ASC-US) • Cannot exclude HSIL (ASC-H) • Low-grade squamous intraepithelial lesion (LSIL) – Includes HPV/mild dysplasia/CIN 1 • High-grade squamous intraepithelial lesion (HSIL) – Includes moderate, severe dysplasia, CIS/CIN 2 and 3 • Squamous cell carcinoma
- 22. 22 Pap Smears 2001 BethesdaSystem • Epithelial cell abnormalities (continued) – Glandular cells • Atypical – Endocervical (Not otherwise specified, or favor neoplastic) – Glandular (not otherwise specified or favor neoplastic) – Endometrial • Endocervical carcinoma in situ • Adenocarcinoma – Endocervical – Endometrial – Extrauterine – Not otherwise specified
- 24. HPV Positive Headand Neck Cancers
- 26. HPV + ByCancer Site Oropharynx Cancer 40.6% , 22.4% Oral Cavity Cancer 14.9%, 4.4% Larynx Cancer 13.4%, 3.5% Oropharynx = tonsil, base of tongue, pharyngeal wall, soft palate Oral Cavity = buccal mucosa, floor mouth, anterior tongue, hard palate studies from the 1990s suggested that approximately 50 percent of oropharyngeal cancers were attributable to HPV, while more recent studies suggest that HPV accounts for 70 to 80 percent of cases in North America and Europe
- 27. Long-term prognosis andrisk factors among patients with HPV-associated oropharyngeal squamous cell carcinoma Cancer Volume 119, Issue 19, pages 3462–3471, 1 October 2013 patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV-OSCC) HPV-OSCC who received treatment at the Johns Hopkins Hospital between 1997 and 2008 and who had tissue available for HPV testing
- 28. Long-term prognosis andrisk factors among patients with HPV-associated oropharyngeal squamous cell carcinoma Cancer Volume 119, Issue 19, pages 3462–3471, 1 October 2013 In total, 157 of 176 patients (90%) with OSCC had HPV-associated disease (HPV- OSCC). In the patients with HPV-OSCC, the 3- year and 5-year OS rates were 93% and 89% respectively.
- 29. Trials of OropharynxCancer Improved Survival with HPV + AuthorSurvival HPV + HPV – Ang 82%/3y 57%/3y Ang 86%/3y 60% Gillison 49%/5y 19.6% Posner 82%/5y 35% Rischin 91%/2y 74% Cancer Control July 2016, Vo.23, No 3
- 30. 5 Year Survivalin 1907 patients with HPV+ oropharyngeal cancer Stage I: 88% II: 82% , III: 84%, and IVA: 81%, IVB: 60% 5-year overall survival did not differ among N0 (80%) N1– N2a (87%), and N2b (83%) subsets, but was significantly lower for those with N3 disease (59% ) So need to change the staging system (only deeply invasive T4b or huge nodes (N3 > 6cm) do poorly Lancet Oncology Volume 17, No. 4, p440–451, April 2016
Editor's Notes
- #20 The best time to schedule your test is 8 to 12 days from the start of your last menstrual cycle.
- #21 In results reported according to the Bethesda 2001 system, the specimen is first reported as to whether it was satisfactory for evaluation; if the specimen was not satisfactory for evaluation, then a new specimen must be gathered. Usually the test would be repeated within the next 2 to 3 months. A smear interpreted to be “negative for intraepithelial lesion” (the reported “normal” and desired result) could still have other findings, for example Trichomonas, yeast, various bacterial concerns, cellular changes consistent with Herpes infection, and cell changes resulting from injury, radiation or inflammation. Epithelial cell abnormalities may either be of squamous cells (the outermost layer of cells) or glandular cells.
- #22 Squamous cells are the cells that cover the majority of the cervix. The potential for malignancy (cancer) increases down this list, squamous cell carcinoma being an invasive cancer. In the case of ASC or ASC-US results, it’s recommended that an HPV test be done on this or an additional sample to determine if the atypical result is related to HPV infection.
- #23 Glandular cells cover the lining of the uterine opening and canal. “Carcinoma in situ” or “Adenocarcinoma in situ” refers to a malignancy that is not yet invasive, that is to say, has not moved into the flesh beyond the surface of the cervix. These abnormalities are much less common than squamous cell abnormalities on a pap smear. Pap smears also may occasionally report other malignancies without necessarily being able to note the originating site of the malignancy. Most diagnoses of a malignancy require conslutation with pathologists and/or specialists. The majority of abnormalities reported on Pap smears are NOT cancer, and are either reversible or treatable and do not progress on to become a malignancy; it is important in the event of an abnormality to get follow-up Pap smears and (as necessary) other testing to monitor the situation and determine if treatment is necessary.