CANCERS LINKED TO HPV

1. HPV AND CANCERS
DR.DIVYA JAIN
CHOITHRAM HOSPITAL
INDORE

2. HUMAN PAPILLOMA VIRUS

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. 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. HPV TRANSMISSION
• Direct skin-to-skin contact
• Usually, but not always sexual contact
• Infected birth canal
• Fomites (very rare)

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. 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

9. 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. HPV DETECTION

11. 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

13. 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

14. 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

15. 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.

17. • 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.

18. 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.

19. •Why does HPV
positive oropharyngeal
cancer have a better
prognosis?

20. WHY HPV +VE PATIENTS DO WELL??

21. 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.

22. REVIEWING MANAGEMENT
STRATEGIES??

23. 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

24. 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.

25. 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.

26. CERVICAL
CANCER

27. • 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

30. 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.

31. Natural History of HPV & Cervical Cancer
Normal
Cervix
HPV
Infection
Pre-cancer Cancer
Infection
Progression Invasion
RegressionClearance
 Persistence

32. CIN: PRE-CANCEROUS
WARNING
• Cervical intraepithelial neoplasia
(CIN) observed in disease
progression
• New, abnormal, disorganized
growth of cervix epithelium

33. 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

34. STAGES OF CIN: HISTOLOGY
NORMAL CIN I CIN II CIN III
Furumoto et al., 2002.

36. 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

37. PREVENTION BETTER THAN
CURE
• PRIMARY PREVENTION-Vaccination against HPV
• SECONDARY PREVENTION-Screening for
precancerous changes (and treatment if problems
found)

38. 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 .

39. 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.

40. HPV VACCINE

41. VACCINATION WITH
GARDASIL OR CERVARIX?

43. 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.

44.  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

45. 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

49. 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.

50. • Should boys be vaccinated?
• Can vaccine be given to pregnant women
/lactating mother?
• Can vaccine be given after development of
cancer?

51. THANK YOU…..