2. - Most common gynecological malignancy
- Fourth mc cancer in women worldwide(After breast,colorectal and lung)
- 2nd most common cancer in india after breast cancer (2020 globocon india)
- Worldwide incidence : 13.3/100000 (GLOBOCAN 2020)
- Most common in women in their 5th-6th decade
- Higher incidence in developing countries /low socioeconomic countries
3. INDIAN DATA
According to national cancer registry programme as on march 2012-2016, (2020
report)
- 6-29% of all cancers in females
- Highest age adjusted incidence is 27.7/lac in Papumpare(arunachal)
- >85% are above 40 yrs
- Maximum cases reported between 50-69 yrs
- Third most common cause of cancer related deaths (~10%)
6. Can be divided into 3 parts
1. Endocervix - Simple columnar epithelium
2. Ectocervix- Stratified non keratinized squamous epithelium
3. Transformation zone - Endocervical reserve cells that differentiating towards
squamous lineage
12. - Family Papillomaviridae
- HPV is a double stranded DNA virus
- Most commonly associated with carcinoma cervix- 16 and 18 (found in 70 % of
cervical cancers)
16. Access to basal membrane through epithelial trauma
Entry into host cell and transfer of viral DNA to nucleus
Integration of viral DNA with host DNA
Translation products are two primary oncogenes E6 & E7
Inhibit tumor suppressor genes (p53 and Rb)
Genome dysregulation , Cell cycle activation, inhibition of
apoptosis and cell immortalization eventually neoplastic
changes
19. ● The link between genital HPV infections and cervical cancer was first
demonstrated in the early 1980s by Harold zur Hausen, a German
virologist. Since then, the link between HPV and cervical squamous
cell carcinoma has become well established.
20. Risk factors :
- Early age of first intercourse (RR- 16 %)
- Multiple sexual partners (RR 3.6%)
- Multiparity
- History of sexually transmitted diseases including chlamydia
and gonorrhea, HSV
- Cigarette smoking may increase risk (RR-4%)
21. ● The greatest risk of HPV infection coincides with greatest metaplastic
activity. Greatest metaplastic activity occurs at puberty and first pregnancy
and declines after menopause.
● Most common in sexually active young women, 18 to 30 years of age.
● Sharp decrease in prevalence after 30 years of age.
● Cervical cancer → more common in women older than 35 years,
● Suggesting infection at a younger age and slow progression to cancer.
● Persistence of infection is more common with the high-risk oncogenic HPV
types and is an important determinant in the development of cervical
cancer.
22.
23. - Some studies have shown HIV infected women
- Increased incidence of HPV infection
- Persistent infection for longer periods
- Faster rate of progression to high grade dysplasia
- Iatrogenic immunosuppression in organ transplant recipients is also associated
with increased prevalence of CIN
24. •Oral contraceptives
➢ Role is controversial
➢ The upstream regulatory region of HPV contains sequences similar to the
glucocorticoid responsive elements that are inducible by steroid hormones such as
progesterone (the active component of oral contraceptives).
27. SCREENING – WHAT IS ITS IMPORTANCE?
● Detects precancerous lesions and early-stage disease
● Treatment of these decreases incidence and mortality
● Systematic reviews and meta analysis of observational studies showed
reduction in Locally Advanced cervical cancer incidence and mortality
● Leading to the adoption of screening programs in all developed and many
developing nations
28. SCREENING- WHY IS IT EFFECTIVE IN CA CERVIX ?
● Easy and direct access of the uterine cervix for examination and sampling.
● Clearly defined viral etiology which could be incorporated as a marker in mass
screening program
● Screening procedure is cheap and highly sensitive.
● Latent period for intraepithelial lesions to transform into invasive carcinoma is 15
to 20 years.
● Effective treatments available for the premalignant changes
31. Concept of triage
● WHO suggests using an HPV DNA primary screening test either with triage
or without triage to prevent cervical cancer among the general population
of women.
● WHO suggests using an HPV DNA primary screening test with triage rather
than without triage to prevent cervical cancer among women living with HIV.
● Among the general population of women or those living with HIV, WHO
suggests using partial genotyping, colposcopy, VIA or cytology to triage
women after a positive HPV DNA test
32. When to start
● Age of 30 years among the general population of women
● At the age of 25 years among women living with HIV
33. Screening interval
● Every 5 to 10 years when using HPV DNA detection as the primary
screening test among the general population of women.
● Every 3 to 5 years when using HPV DNA detection as the primary screening
test among women living with HIV.
34. When to stop
● After the age of 50 years, WHO suggests screening is stopped after two
consecutive negative screening results consistent with the recommended
regular screening intervals among both the general population of women and
women living with HIV.
35. Based on availability of tests
● Where HPV DNA testing is not yet operational, WHO suggests a regular
screening interval of every 3 years when using VIA or cytology as the
primary screening test, among both the general population of women and
women living with HIV.
● As programmes introduce HPV DNA testing, use this test at the woman’s next
routine screening date regardless of the test that was used at prior screening.
● In existing programmes with cytology or VIA as the primary screening test,
rescreening with the same test should be continued until HPV DNA testing is
operational among both the general population of women and women living
with HIV.
36. Discordance between primary and triage
● WHO suggests that the general population of women who have screened
positive on an HPV DNA primary screening test and then negative on a
triage test are retested with HPV DNA testing at 24 months and, if negative,
move to the recommended regular screening interval.
● WHO suggests that women from the general population and women living
with HIV who have screened positive on a cytology primary screening test
and then have normal results on colposcopy are retested with HPV DNA
testing at 12 months and, if negative, move to the recommended regular
screening interval.
37. Post treatment screening
● WHO suggests that women from the general population who have been
treated for histologically confirmed CIN2/3 or adenocarcinoma in situ
(AIS), or treated as a result of a positive screening test are retested at 12
months with HPV DNA testing when available, rather than with cytology or
VIA or co-testing, and, if negative, move to the recommended regular
screening interval.
45. FUTURE trials
•12,167 women
•15 to 26 years
•Three doses of either HPV-6/11/16/18 vaccine or
placebo
•day 1, month 2, and month 6
•The primary composite end point was cervical
intraepithelial neoplasia grade 2 or 3,
adenocarcinoma in situ, or cervical cancer related to
HPV-16 or HPV-18.
•3yrs follow up
•vaccine efficacy against all high-
grade cervical lesions, regardless of
causal HPV type, in this intention-to-
treat population was 17% (95% CI, 1
to 31)
46. Conclusion drawn
● These data demonstrate that a quadrivalent HPV-6/11/16/18 vaccine was
highly effective in preventing high-grade cervical lesions associated with
HPV-16 and HPV-18.
● Widespread immunization of female children and adolescents may result in a
substantial decrease in HPV-16–related and HPV-18–related cervical
disease, including cervical cancer.
● Since women with human immunodeficiency virus infection or other
immunosuppressive conditions were not enrolled in our study, future trials will
be needed to evaluate safety and efficacy in these populations.
48. -Healthy women
-15–25 years
-no more than six
lifetime sexual
partners
HPV-16/18 AS04-adjuvanted vaccine VS control
hepatitis A vaccine
PATRICIA end-of-study results show excellent
vaccine effi cacy against CIN3+ and AIS irrespective
of HPV DNA in the lesion. Population-based
vaccination that incorporates the HPV-16/18
vaccine and high coverage of early adolescents
might have the potential to substantially reduce the
incidence of cervical cancer.
49. Choice of HPV vaccine
● Current evidence suggests that from the public health perspective the
bivalent, quadrivalent and nonavalent vaccines offer comparable
immunogenicity, efficacy and effectiveness for the prevention of cervical
cancer, which is mainly caused by HPV types 16 and 18.
● Choice based on the assessment of locally relevant data and on a number
of factors, including the scale of the prevailing HPV associated public health
problem (cervical cancer, other HPV associated cancers, or ano-genital
warts) and the population for which the vaccine has been approved.
● Decision-makers should also consider unique product characteristics, such as
price and programmatic considerations.
