Summarized content of HPV Indication

1. HPV Vaccine Done By: Khalid Houbani
Family Medicine Resident

2. Why I choosed this Topic?
• is a very common virus that can cause cancers later in life. Nearly 42 million
people are currently infected with HPV in the United States. About 13 million
people, including teens, become infected with HPV each year.
• In the U.S., nearly 36,000 people are estimated to be affected by a cancer
caused by HPV infection each year. While there is screening for cervical cancer
that can detect cancer early, there is no recommended screening for the other
cancers caused by HPV infection, like cancers of the back of the throat, anus,
penis, vagina, or vulva.
• HPV vaccination provides safe, effective, and lasting protection against the HPV
infections that most commonly cause cancer.

3. Epidemiology
HPV are members of a family of small, non-enveloped papillomaviruses
having a double-stranded DNA (dsDNA) genome. Composed of approximately
7.9 kilobases (kb) [4], all HPVs infect either the cutaneous or mucosal surfaces
of epithelial cells. Approximately 189 HPV genotypes
the 30–40 types from the α-genus of HPVs that infect the human genital tract
can be subdivided into low- and high-risk types
HPV6 and 11. These low-risk viruses have been associated with benign anogenital warts or condylomata
By contrast, at least 12 high-risk HPV (HRHPV) types, HPV16, -18, -31, -33, -35, -39, - 45, -51, -52, -56, -58 and -59,
have been associated with anogenital cancers as well as precursor neoplastic lesions

4. • Most HPV types (approximately 80) infect the cutaneous epithelium
(nonmucosal) and cause skin warts on the hands and feet.
• About 40 types infect the mucosal epithelium, including > 12 high-risk
(oncogenic) types.
Infection occurs in both men and women, with the highest prevalence in women
aged 20-25 years.

5. In Saudi Arabia
• The incidence of HPV infection in Saudi Arabia is controversial; some
researchers claim that HPV infection in Saudi Arabia has the lowest rate in
the world (1.9 cases/100,000 women), whereas others claim that the rate of
HPV infection among Saudi women is high
• Among those studies claiming high prevalence of HPV in Saudi Arabia there
is a recent one that described screening of 519 cervical specimens using PCR
and a reverse blot hybridization assay. Authors found that 164 (31.6%) of the
specimens were positive for HPV
• Among those 164 HPV-positive specimens, 130 showed normal cytology,
while 32 showed atypical squamous cells of undetermined significance

6. • A recent observational, epidemiological cross-sectional study conducted
between April 2010 and December 2011 at three hospitals in Saudi Arabia
investigated the prevalence of HPV in women aged ≥ 15 years who were
attending routine gynecological examinations
• The HPV test was conducted using polymerase chain reaction:
• in a group of 417 women, HPV-DNA was detected in 9.8% women. The most
prevalent HR-HPV types were HPV-68/73, HPV-18, and HPV-16, while the
most common LR-HPV types were HPV-6, HPV42, HPV-53, and HPV-54

7. • Another study described a relatively high prevalence of HPV-16 or HPV-18
cervical infections among women attending a family medicine clinic in
Riyadh (capital city of Saudi Arabi
• Overall, the HPV-16/18 prevalence was 31.6%.

8. Risk Factors
• being sexually active
• increased number of different sexual partners
• young age at sexual initiation
• being uncircumcised (for both the male and his female partner)
• decreased condom use
• history of other sexually transmitted infections

9. Transmission
• Cutaneous infection is transmitted by contact with viral particles, either
through direct contact with existing wart or fomites.
• Infection is usually self-limited and asymptomatic, but when present,
clinical manifestations include:
• common, flat, anogenital, periungual, and plantar warts
• malignancies including cervical, vaginal, vulvar, anal, penile, and
oropharyngeal cancers
• skin lesions in patients with epidermodysplasia verruciformis, which may
progress to cutaneous squamous cell carcinoma
• Cervical or anogenital HPV infection may increase risk of HIV acquisition.

10. HPV screening methods
• An HPV infection is diagnosed mainly using molecular biological methods
because culturing and in vitro propagation of viruses are impractical and
serological methods are insufficiently sensitive
• DNA-based assays (e.g., PCR, in situ hybridization,)
• RNA-based assays (e.g., mRNA gene expression and protein assays).

11. HPV DNA testing as part of routine
cervical cancer screening
• American Cancer Society (ACS) recommends: individuals aged 25-65 years at
average risk for cervical cancer, but if not available, cotesting (HPV testing in
conjunction with cervical cytology) every 5 years or cytology alone every 3 years
is acceptable
• American College of Obstetricians and Gynecologists (ACOG) and United
States Preventive Services Task Force (USPSTF) recommends: HPV DNA
testing for high-risk (oncogenic) HPV types and/or cervical cytology for women
aged 30-65 years
• if cotesting (preferred) performed, repeat testing after 5-year interval if both results are normal
• for women who are cytology negative, but HPV-positive
• repeat both tests in 12 months
• for women positive for HPV 16/18, refer directly for colposcopy

12. HPV Vaccine
• 9-valent HPV vaccine (9vHPV, Gardasil 9) is the only HPV vaccine distributed in
the United States as of late 2016.
• Quadrivalent (4vHPV, Gardasil) and bivalent (2vHPV, Cervarix) HPV vaccines
are available in some countries outside of the United States.

13. Indications for HPV vaccine
• For females, any HPV vaccine (9vHPV, 4vHPV, or 2vHPV) is recommended
routinely at age 11-12 years, or up until age 26 years if not started previously.
• For males, either 9vHPV or 4vHPV is recommended routinely at age 11-12
years, or up until age 21 years if not started previously.
• The World Health Organization (WHO) recommends vaccination of females
aged 9-14 years before the onset of sexual activity. Vaccination of other
populations, including females ≥ 15 years old and males, should only occur
when feasible, affordable, and not diverting resources away from primary target
population.
• The Centers for Disease Control and Prevention (CDC) Advisory Committee on

14. According to MOH

16. Vaccine Selection
• 9vHPV, 4vHPV, or 2vHPV can be used for :
• routine vaccination of females aged 11 or 12 years
• females aged 13-26 years who have not been vaccinated previously or who have not
completed 3-dose series
• 9vHPV or 4vHPV can be used for:
• routine vaccination of males aged 11 or 12 years
• males aged 13-21 years who have not been vaccinated previously or who have not
completed the 3-dose series

17. • either 9-valent HPV or quadrivalent HPV vaccination is recommended for men
who have sex with men and patients who are immunocompromised (including
patients with HIV infection) through age 26 years if not vaccinated previously

18. Timing and schedule of vaccination
• vaccination series can be started beginning at age 9 years
• HPV vaccines may be given in 2-dose or 3-dose schedules
• 2-dose vaccine series (given at 0 and 6-12 months) recommended for females
and males initiating HPV vaccination between ages 9-14 years (excluding
immunocompromised patients)

19. • 3-dose vaccine series (given at 0, 1-2, and 6 months)
• recommended for
• females initiating HPV vaccination between ages 15 and 26 years
• males initiating HPV vaccination between ages 15 and 21 years, with extension to 26 years in men
who have sex with men or in transgender persons
• females and males
• aged 9-14 years who had first 2 doses < 5 months apart
• aged 9-26 years with primary or secondary immunocompromising conditions that may reduce
humoral or cell-mediated immunity such as
• HIV infection
• T lymphocyte complete or partial defects
• B lymphocyte antibody deficiencies
• malignant neoplasms
• transplantation
• autoimmune disease
• immunosuppressive therapy

20. Minimum Dosing Interval
•dosing intervals for 9-valent HPV, quadrivalent HPV, and
bivalent HPV vaccines minimum interval between first and
second doses of HPV vaccine is 4 weeks
•minimum recommended interval between second and
third dose of vaccine is 12 weeks
•minimum interval between first and third dose is 5 months

21. interrupted schedules
• if vaccine schedule is interrupted resulting in longer-than-recommended dosing
interval, vaccine series does not need to be restarted
• if interval between first and second dose in 2-dose series is < 5 months, a third
dose is recommended
• if series is interrupted after first dose, second dose should be administered, and
second and third doses should be separated by interval of ≥ 12 weeks

22. for individuals not vaccinated at
recommended age
• females aged 13-26 years and for males aged 13-21 years who have not been
vaccinated previously or who have not completed 3-dose series; males aged 22-
26 years may be vaccinated
• if females or males reach age 27 years before vaccination series is complete,
second and/or third doses of vaccine can be given after age 26 years to
complete vaccination series
• prevaccination assessments (such as Pap testing or screening for high-risk HPV
DNA, type-specific HPV DNA tests, or HPV antibody tests) to establish
appropriateness of HPV vaccination are not recommended

23. Contraindications and
precautions
hypersensitivity or allergy to vaccine
components:
• quadrivalent HPV vaccine is produced in Saccharomyces cerevisiae (baker's
yeast) and is contraindicated for patients with history of immediate
hypersensitivity to yeas
• the tip cap of prefilled syringes of bivalent HPV vaccine might contain latex;
bivalent HPV vaccine should not be used in patients with anaphylactic allergy to
latex

24. acute illnesses:
HPV vaccines can be given to patients with minor acute illnesses (such as
diarrhea or mild upper respiratory tract infections with or without fever
vaccination of patients with moderate or severe acute illnesses should be deferred
until after patient improves

25. vaccination during pregnancy
• HPV vaccines are not recommended for use in pregnant women
• HPV vaccines have not been associated causally with adverse outcomes of
pregnancy or adverse events in developing fetus, however, if a woman is found to be
pregnant after initiating vaccination series, the remaining doses should be delayed
until completion of pregnancy
• pregnancy testing is not needed before vaccination
• f a vaccine dose has been administered during pregnancy, no intervention is needed
and vaccine series should resume postpartum with next scheduled dose
• patients and healthcare providers should report an exposure to HPV vaccine during
pregnancy to VAERS

26. Vaccine interchangeability
• no studies address interchangeability of HPV vaccines, however, no theoretical
reason to expect an increased risk for adverse events if series included > 1
product
• HPV vaccination series should be completed with same HPV vaccine product
whenever possible
• in females - if vaccination providers do not know or do not have available HPV
vaccine product previously given, any HPV vaccine product (9-valent [9vHPV],
quadrivalent [4vHPV], or bivalent [2vHPV] HPV vaccines) may be used to
continue or complete series to provide protection against HPV 16 and HPV 18

27. • effectiveness of a series that contained > 1 product might be reduced compared
with a complete series with 1 product for protection against HPV 16/18-related
cancers and precancers
• for persons who have had adequate vaccination with 4vHPV or 2vHPV, there is
no Advisory Committee on Immunization Practices (ACIP) recommendation
regarding additional vaccination with 9vHPV

28. Special populations
• 1-patients with abnormal Pap test, known HPV infection, anogenital warts, or
HPV-associated lesions
• HPV vaccination can provide protection against infection with HPV vaccine
types not already acquired, therefore, vaccination is recommended through
recommended age for
-women regardless of an abnormal Pap test result
-women or men regardless of known HPV infection, HPV-associated precancer
lesions, or anogenital warts

29. • women who have abnormalities on cervical cancer screening are likely to be
infected with ≥ 1 genital HPV types
• with increasing severity of Pap test findings, likelihood of infection with HPV 16
or HPV 18 increases and expected benefit of vaccination decreases

30. • 2- patients who are immunocompromised
• patients who are immunocompromised because of transplant, medications, or
HIV have a higher burden of HPV-associated disease and cancer
• although studies have found vaccines to be well tolerated and immunogenic in
patients with HIV-infection, some studies found that geometric mean titers
(immunogenicity) were lower among patients with HIV-infection compared to
patients who are not infected
• routine vaccination with 3-dose series is recommended at age 11 or 12 years for
patients who are immunocompromised
• vaccination is recommended through age 26 years for immunocompromised
patients who have not been vaccinated previously or who have not completed 3-
dose series

31. • 3- men who have sex with men
• men who have sex with men are at high risk for infection with HPV and
associated conditions, including anogenital warts and anal cancer
• routine vaccination is recommended
• vaccination is recommended through age 26 years for men who have not been
vaccinated previously or who have not completed 3-dose series

32. • 4- history of sexual abuse or assault
• females and males who are victims of sexual abuse or assault should receive
HPV vaccine through recommended ages if they have not already been
vaccinated
• healthcare providers who evaluate and treat children and youth who are
suspected or confirmed victims of sexual abuse or assault should be aware of
need for HPV vaccination
• HPV vaccination recommended beginning at age 9 years for children and youth
with any history of sexual abuse or assault who have not initiated or completed
3-dose series
• 5- lactating women can receive any HPV vaccine

33. Efficacy
• There is high-certainty evidence that HPV vaccines protect against cervical
precancer in adolescent girls and young women aged 15 to 26. The effect is
higher for lesions associated with HPV16/18 than for lesions irrespective of HPV
type. The effect is greater in those who are negative for hrHPV or HPV16/18
DNA at enrolment than those unselected for HPV DNA status.

34. Adverse Effects
• reported adverse effects with bivalent HPV vaccine (2vHPV):
• local adverse effects include
• pain
• redness
• swelling
• induration
• generalized adverse effects include
• fatigue
• headache
• dizziness
• fever
• rash
• myalgia
• arthralgia
• urticaria
• gastrointestinal symptoms (including nausea, vomiting, diarrhea, and/or abdominal pain)

35. • reported adverse effects with quadrivalent HPV vaccine (4vHPV):
• local adverse effects include injection site pain and redness
• generalized adverse effects include
• syncope (fainting)
• dizziness
• headache
• fever
• pallor
• loss of consciousness
• gastrointestinal symptoms (including nausea and vomiting)

36. References
• CDC
HPV Vaccine Administration | CDC
• MOH
Communicable Diseases - HPV (Human Papillomavirus) (moh.gov.sa)
• Oxford Handbook of obstetric and gynecology 3rd Edition
• Dynamed
Human Papillomavirus (HPV) Vaccine (dynamed.com)