Hpv and cancers
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HPV AND CANCERS
DR.DIVYA JAIN
CHOITHRAM HOSPITAL
INDORE
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HUMAN PAPILLOMA VIRUS
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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.
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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
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HPV TRANSMISSION
• Direct skin-to-skin contact
• Usually, but not always sexual contact
• Infected birth canal
• Fomites (very rare)
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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
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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
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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
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HPV DETECTION
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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
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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
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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
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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.
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• 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.
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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.
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•Why does HPV
positive oropharyngeal
cancer have a better
prognosis?
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WHY HPV +VE PATIENTS DO WELL??
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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.
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REVIEWING MANAGEMENT STRATEGIES??
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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
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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.
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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.
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CERVICAL CANCER
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• 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
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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.
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Natural History of HPV & Cervical Cancer
Normal
CervixHPV
InfectionPre-cancer Cancer
InfectionProgression Invasion
RegressionClearance
Persistence
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CIN: PRE-CANCEROUS WARNING
• Cervical intraepithelial neoplasia(CIN) observed in disease progression
• New, abnormal, disorganized growth of cervix epithelium
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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
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STAGES OF CIN: HISTOLOGY
NORMAL CIN I CIN II CIN III
Furumoto et al., 2002.
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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
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PREVENTION BETTER THAN CURE
• PRIMARY PREVENTION-Vaccination against HPV
• SECONDARY PREVENTION-Screening for
precancerous changes (and treatment if problems
found)
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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 .
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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.
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HPV VACCINE
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VACCINATION WITH GARDASIL OR CERVARIX?
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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.
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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
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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 vaccine1. 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
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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.
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• Should boys be vaccinated?
• Can vaccine be given to pregnant women
/lactating mother?
• Can vaccine be given after development of
cancer?
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THANK YOU…..