HPV and its prevention

1. HPV
Dr Menaal Kaushal
JR II
Department of S P M

2. Contents
Introduction
Problem Statement
Clinical manifestation
Screening
Prevention- Vaccination, Condom, Circumcision
Special Cases& Controversies:
Girls 9- 12 years
Unmarried Girls 13- 26 years
Unmarried older women
Married HPV negative women
HPV positive women
Men

3. Introduction
ds- DNA virus- Papillomavirus
>100 HPV types
Needs keratinocytes- “Skin virus”
Skin or
Mucous membranes- about 40 genital HPV types
Of which, 15-18 genital types associated with cancer

4. HPV Classification
“Low Risk”
HPV
Genital warts
Low grade cervical
dysplasia
“High Risk”
HPV
Low and high
grade cervical
dysplasia
Cervical Cancer

5. Cervical Dysplasia Classification
Low Risk HPV
Histology of Cervical
Squamous Epithelium
Basal Cell Layer
Basement Membrane
High Risk HPV

6. High and Low Risk HPV
Oncogenic
Clinical
Potential Manifestations
Types
Low
CIN I
Genital warts
6, 11
Low
CIN I
40,42,43,44,54
55,57,61,84
High
CIN I-III
carcinoma
16,18,31,33,35,
39,45,51,52,56,
58,59,68,73,82

7. Detection of HPV Types in Cervical
Cancer
11.4
16
18
45
31
33
58
52
35
Others
0.4
0.6
3.20.2
3.9
3.3
54.9
22.1
Europe
Europe
0.5
0.5
4.4 0.5 2.2
0.8
4.2 0.8
4.4
4.2 2.9
Asia
16
18
0.5 13.5
20.8
16
16
45
18
18
45
45
31
5.4
2.9
56
17.2
4.2
31
33
58
1
3.4
Africa
17.2
2
16
4.5
56
1.4
52
35
Others
15.3
43.4
31
33
58
33
58
52
35
Oth
13
3.3
52
16
31
3.1
2
17.5
1.6
Latin America
18
45
18
35
33
58
Others
1.6
2.6
45
7.9 31
2.9
4
51.7
7
5.5
10.6
50.2
52
14.1
33
35
58
52
Others
35
Others

8. Genital HPV is
Problem Statement
EVERYWHERE!
Human papillomavirus (HPV) is an extremely common
STD, with an estimated 80 percent of sexually active
people contracting it at some point in their lives;
Incidence: 14 million new infections occur yearly.
Prevalence: About 79 million people (both men and
women) are thought to have an active HPV infection at
any given time.
SKIN contact, not body fluids

9. In India
In India, Ca Cervix is the No 1 cancer among women,
with an incidence of 27.0 per 100,000 women and an
age standardized mortality rate as high as 45.2 per
100,000 women (2008)

10. Epidemiologic Relationships of
HPV
Well Established:
Cervical Dysplasia and Cancer
Genital Warts
Recurrent Respiratory Papillomatosis
As well as:
Anogenital cancers (vulvar, penile, vaginal)
Head and Neck Cancer (esophagus, pharynx)

11. In the West, 30% of oral carcinoma is related to HPV. It
is commonly seen in ages 20- 39 years
The risk of contracting oropharayngeal cancer (cancer of
the tonsils, back of throat or base of the tongue)
heightens 3.4 times with 6 or more oral sex partners
The survival rate for those with HPV-positive head and
neck tumors is 85% in non-smoking people. The survival
rate drops down to 45-50% for smokers.

12. Global Perspective on Cervical
Cancer
2nd most common cancer in women
The cancer that kills more women on a world wide basis every
year
>250,000 women die each year world wide
One woman dies every two minutes from cervical cancer
Leading cause of death from cancer in developing countries

13. HPV Transmission
Sexual- Intercourse
•
Genital (non-penetrative), oral, digital contact (skin to skin
contact)
•
Condoms help, but not completely protective
Non-sexual
•
Mother to newborn (vertical transmission - rare)
•
Possibly via fomites (underwear, equipment)
•
Can be seen in virgins (rare)
SKIN contact, not body fluids

14. Clinical Manifestation
Symptomatic
• Persisted
Asymptomatic
• Cleared
If an HPV infection is persistent past the age of
30, there is a greater risk of developing cervical

16. Most HPV Infections Resolve
HPV “Clearance”
•
80- 90% of infections will resolve in 2 years
•
Average duration of infection 9- 13 months
•
Unclear if virus is eradicated or latent
HPV “Persistence”
•
10- 20% of infections persist
• Major risk factor for developing cancer
•
Risk factors for persistence not well understood
* Clearance and persistence is age related

17. Age-related Trends in HPV
Infection in Women
Mean Prevalence
2.5
2
1.5
Oncogenic
Non-oncogenic
1
0.5
0
<25 25- 3534 44
45- 55- >65
54 64
Age group

18. Age Specific Rates of HPV-Related
Genital Cancers in the U.S.
20
Cervix
Vulva
15
Penis
10
Anus
Female
Vagina
5
Anus Male
Age Range in Years
85+
80-84
75-79
70-74
65-69
60-64
55-59
50-54
45-49
40-44
35-39
30-34
25-29
20-24
0
15-19
Incidence per 100,000
25

19. HPV During Adolescence
Risk of Genital HPV Infection from Time of First Sexual Intercourse
1
Cumulative Incidence of HPV
0.9
0.8
0.7
~50%
Cumulative
Incidence
0.6
0.5
0.4
0.3
0.2
0.1
0
0
4
8
12
16
20
24
28
32
36
40
44
Months Since First Intercourse
48
52
56
60

20. HPV in Adolescence
Of all new HPV infections, 74% occur in the 1524 year old age group
Adolescents particularly vulnerable
• Biological:
• Immune immaturity
• Large transformation zone of cervix
• Behavioral (In the West)

21. Why are Adolescent Women More
Susceptible to HPV?
Large transformation zone

22. The New ACOG Screening Guidelines
(Oct 2012)
Pap tests should begin at age 21, regardless of sexual history
Pap testing should not be done for most women more often
than every 3 years- NO traditional "annual Pap" regimen,
but those with abnormal Paps will be tested more often
(yearly)
Rather than using a Pap test alone, HPV/Pap co-testing is
now the preferred method of screening women age 30 and
over.
Such co-testing should only occur once every 5 years with
women who have normal test results

23. HPV testing should NOT be done in women under age 30 other
than as follow-up to unclear Pap test results
Cervical cancer screening can end for most women at age
65, provided she has no history of cervical pre-cancer or
cancer, and has had at least three consecutive, normal Pap tests (or
two normal HPV tests) within the last 10 years.
Women at greater risk for cervical cancer (e.g., those with a history
of cervical pre- cancer or cancer and those who are HIV-positive or
otherwise have weakened immune systems) may require screening
more frequently

25. HPV VLP Vaccines
Bivalent (Cervarix) :
{0, 1, 6}
HPV 16
HPV 18
70% of Cervical Ca
ASO4 Adjuvant (MPL + Alum)
Quadrivalent (Gardasil) : HPV 16
{0, 2, 6}
HPV 18
70% of Cervical Ca
HPV 6
HPV 11
90% of Genital Warts
Aluminum as adjuvant
IM Injections at 0, 1 or 2, and 6 months

26. Vaccine Schedule
Dosing schedules with the vaccines are at 0, 1 to 2
months, and 6 months.
Minimum intervals are 4 weeks between doses 1 and
2, 12 weeks between doses 2 and 3, and 24 weeks
between the first and third doses.
It is likely that variations in scheduled doses do not
seriously impair the vaccines’ effectiveness; therefore, the
vaccine series should not be restarted if the schedule is
interrupted.

28. Assembly of HPV VLPs
Structural model of papillomavirus VLP*
VLP
(~20,000 kD)
L1 Protein
(55–57 kD)
L1 Capsomere
(~280 kD)
5 x L1
VLP = Virus- like particle
72
Capsomeres

29. IMMUNOGENICITY RESULTS (PER PROTOCOL POPULATION):
HPV; VLP; PCR

30. Immunologic Titers To HPV 6, 11, 16, & 18 After
Vaccination
HPV 6
HPV 16
HPV 11
HPV 18

31. Sustained Seropositivity And High Antibody Levels
Up To 4.5 Years
log (EU/ml)
10000
HPV-16
100%
% seropositive
100%
1000
99.7%
Vaccine HPV-16 IgG
Placebo HPV-16 IgG
99%
100%
99%
100%
100%
17 fold
higher
100
Natural
Infection
10
6% 0%
17%
0%
0%
10%
10%
12%
11%
12%
1
month 0
month 7
month 12 month 18 [M25-M32] [M33-M38] [M39-M44] [M45-M50] [M51-M53]
Initial efficacy
Extended follow up
Months follow up time

32. Sustained Seropositivity And High Antibody Levels
Up To 4.5 Years
log (EU/ml)
HPV-18
10000
% seropositive
100%
100%
1000
99.7%
Vaccine HPV-18 IgG
Placebo HPV-18 IgG
99%
99%
99%
100%
100
14 fold
higher
Natural
Infection
10
10%
100%
17%
0%
0%
0%
7%
12%
16%
13%
9%
1
month 0
month 7
month 12 month 18 [M25-M32] [M33-M38] [M39-M44] [M45-M50] [M51-M53]
Initial efficacy
Extended follow up
Months follow up time

33. Efficacy Against Incident Infection by
Other High Risk HPV Types
HPV16/18 Vaccine: ITT Analysis
HPV Type
# Vaccine
# Placebo
Efficacy
(95%CI)
16
1
16
94 (53-99)
18
0
5
100 (24-100)
45
1
17
94 (63-100)
31
14
30
54 (11-78)
33
12
13
1 ( <0 - 61)
52
40
48
19 (-27 - 48)
58
14
16
14 (-88 - 61)

34. Phylogenetic Tree Anogenital HPV
Types
6 11
2
57 3
10
13
7 40
44
43
32 42
Low-risk
HPV types
30
16 35
31
33 58
52
34
18 45 39 68
53 56 66
26 51
High-risk
HPV types

35. Estimated Distribution of Time
Participants Remained Free of HPV

36. SPECIAL SITUATIONS
Equivocal or abnormal Pap test OK
Positive HPV test OK
Genital warts OK
Immunosuppression OK
Lactating women OK

37. Precautions and Contradictions
Moderate or severe acute illnesses: should be
deferred until after the illness improves
History of hypersensitivity or severe allergic
reaction to yeast or to any vaccine component
Pregnancy

38. Key Issues Remaining
Pap smear screening recommendations will NOT change.
Only HPV 16/18 are included in the vaccine; 13 other types
implicated in Cervical Cancer
Should older women (>26 years of age) be vaccinated?
YES, older women who are not with abnormal Pap, and not
currently HPV infected, can be vaccinated

39. HPV Among Boys
When the percentage of girls getting vaccinated are in the 30 to 40
percent range, vaccinating boys is suggested to have a substantial
enhancing impact on trying to protect those girls who are not
vaccinated.
This would provide "herd immunity." Boys don't get cervical cancer,
but they can transmit HPV. So vaccinating boys would reduce the
amount of HPV circulating in the population

42. Increasing Incidence of Anal Cancers

46. Thank You