2. HPV Structure
Non Enveloped Double Stranded DNA Virus
Small DNA viruses with
about 7900 base pairs
6 early (E) and 2 late (L)
proteins
L1-capsid protein
**E6 and E7 are
oncogenic
!Each type has less than
90% base pair
homology with any
other type
3. HPV TYPES
►The common HPV types can be divided into
three major categories based on their
oncogenic potential:
1.Low risk HPV-6,11,42,43,44
►
►
2.Intermediate risk HPV-33,35,39,52,58
3.High risk HPV-16,18,31,45
13. HPV GENOMIC
ORGANIZATION
➢
➢
➢
►
►
►
►
Upstream regulatory region (URR)
Early region
Late region
URR regulates viral replication
Early region- Transcribes proteins that is
helpful to program the host cell to
produce new viral DNA
Late region- encodes proteins for the
capsid that surround like DNA core to
produce the complete viron molecule.
With all these mechanisms, the virus
takes over the control of infected
epithelial cells.
► The virus then entirely controls the host
cell mechanism to produce new viral
DNA and viral proteins.
14. Host Immune Response
Humoral
► There is development of HPV specific neutralizing
antibodies either of immunoglobulin IgA and IgG
► These antibodies prevent infection of anogenital
mucosal surface.
► These are detected against L1 & L2 HPV capsid
protein.
15. Cell Mediated Immunity-
► Whenever the pathogens enter the human cell-Cell
Mediated immunity ( CMI) mechanism is switched on in
following way.--------
► Specific CD8 +, cytotoxic T lymphocytes , CD4 and Helper
T lymphocytes are activated and play important role,
required to clear the infected cells.
► Cytotoxic T lymphocytes (CTL) recognise the early
proteins in the infected cells in conjuction with host major
histocompatibility complex (MHC) class I molecule.
► Helper T cells recognise longer peptide fragments
complexed with MHC class II molecules.
► Both these cytotoxic T lymphocytes and Helper T
lymphocytes promote specific antibody production through
cytokines induction.
16. About 80%of Women
will be infected with
HPV in their lifetime
HPV and Cervical Cancer
Source: Gynecologic Cancer Foundation
18. HPV AND CERVICAL
NEOPLASIA
► Infections with HPV cause approximately 5% of the global
burden of human cancers and at least 500,000 deaths
annually .
Infection with specific HPV (16,18) types is necessary for
the development of the vast majority of cervical cancers
(>99.7%) and the immediate precursor lesion (CIN 3) .
The magnitude of the association between HPV and
cervical cancer is higher than the association between
smoking and lung cancer.
19.
20. ► The four major steps in the development of cervical cancer
are-
(i)infection of the metaplastic epithelium of the
transformation zone with one or more carcinogenic HPV
types;
(ii)viral persistence rather than clearance reflecting the host
immune response;
(iii)clonal progression of persistently infected epithelium to
cervical precancer (CIN 3); and progression to
(iv) clinical cancer (macro and micro invasion).
22. HPV – PATHOGENISIS OF
CERVICAL CANCER
The HPV genome is usually maintained as a stable viral episome, independent
of the host cell genome, in the nucleus of infected cells.
It codes for only eight genes .
In some high-grade CIN lesions, and more frequently in cervical cancer, HPV
genomes are covalently bonded or integrated into the host chromosomes .
This integration event occurs at random within the host cell genome but is
highly specific in relation to the viral genome, involving the E1 and E2 genes,
with important consequences for regulation of viral gene expression .
This integration of the HPV genome into the host genome is associated with
invasive cancer and might serve as an important biomarker to distinguish HPV
infection from precancer .
23. ►The late genes, L1 and L2, the sequences
of which are highly conserved among all
papilloma viruses, encode the common
capsid proteins.
These viral proteins reflect late viral gene
expression and are exclusively present in
well-differentiated keratinocytes .
Both proteins play an important role in
mediating efficient virus infectivity.
24. The proteins encoded by the E6 and E7 genes of high-risk HPV types,
particularly HPV 16 (clade A9) and 18 (clade A7), are directly involved
in cellular transformation in the presence of an active oncogene .
E6 and E7 are the primary HPV oncoproteins with numerous cellular
targets .
Both E6 and E7 proteins can immortalize primary keratinocytes from
cervical epithelium and can influence transcription from viral and
cellular promoters .
The activity of these viral oncoproteins results in genomic instability,
leading to the malignant phenotype.
E6 proteins of high-risk HPV types bind the tumor suppressor protein
p53 .
This induces ubiquitination and degradation of p53, removing the p53-
dependent control of the host cell cycle.
25. ► E6 also increases telomerase activity in keratinocytes
through increased transcription of the telomerase catalytic
subunit gene (hTERT) through induction of c-myc .
Telomerase activity is usually absent in somatic cells,
leading to shortening of telomeres with successive cell
divisions and to eventual cell senescence. E6 mediation of
telomerase activity may predispose to long-term infection
and the development of cancer.
Recently E6 and E7 viral oncogenes have been shown to
antagonize BRCA-mediated inhibition of the hTERT
promoter .
►
26. ► The E7 gene product is a nuclear phosphoprotein that associates with
the product of the retinoblastoma gene (pRb), which is a tumor
suppressor gene important in the negative control of cell growth .
E7 is the primary transforming protein.
Degradation of p53 by E6 and the functional inactivation of pRb by E7
represent the main mechanisms whereby expression of HPV E6 and
E7 oncoproteins subverts the function of the negative regulators of the
cell cycle .
Deregulated expression of the viral oncogenes is a predisposing factor
to the development of HPV-associated cancers.
27. ► The products of the E2 gene are involved in transcriptional
regulation of the HPV genome.
The process of HPV integration into the cellular genome,
which occurs in some high-grade CIN lesions and most
invasive cervical cancers, disrupts the E2 gene .
This results in increased levels of E6 and E7 expression,
correlating with increased immortalization activity .
Both E6 and E7 proteins are expressed at low levels in the
process of HPV infection
28. ► Low-risk HPV types, particularly HPVs 6 and 11 (clade A10), are
associated with condylomata acuminata of the genital tract in both
sexes.
HPV 6 and 11 are also detected alone in low-grade cervical lesions
(exophytic condylomata acuminata, subclinical HPV infection, CIN 1
and some CIN 2 lesion.
These viruses do not appear to induce malignant transformation; they
are unable to integrate into the human genome.
The E6 and E7 proteins of “lowrisk” HPV types only weakly bind p53
and pRb and thus do not immortalize keratinocytes in vitro.
29. ►HPV- 16
Human papillomavirus 16 is the HPV type universally
detected with greatest frequency in high-grade
intraepithelial neoplasia and invasive cancers.
HPV 16 is associated with 50% of cervical squamous
cancers and more than 30% of adenocarcinomas .
It is present in more than 80% of high-grade cervical,
vaginal, vulvar, perianal, and penile preinvasive lesions.
It is detected in more than 25% of low-grade cervical
lesions, 40% of subclinical vulvar HPV infections, and 10%
of genital condylomata acuminata, particularly the
recalcitrant lesions .
30. ►HPV 18 the second most common (25%)
HPV type in invasive cervical cancer, but is
uncommon (5%) in preinvasive cervical lesions .
The association of HPV 18 with aggressive
adenocarcinomas, particularly in younger women,
and the underrepresentation of this viral type in
preinvasive lesions have raised concerns that
HPV 18 may be associated with “rapid-transit”
cancers that escape reliable cytologic detection
31. ► Although the true prevalence of cervical HPV infection is
unknown, it is the most common sexually transmitted
infection, with most sexually active women younger than 35
years of age exposed.
► HPV prevalence and incidence peak in women under 20
years of age and decline in women over 30, secondary to
HPV clearance, with most women in the world exposed to
one or more genital HPV types during their sexual life
32. CLEARANCE OF HPV
►The median time to clearance of HPV
infection in an immunocompetent woman is
6 to 18 months (average of 12 months) with
90% of women clearing a specific HPV-type
after 2 years of observation
33. ►Viral clearance is not often associated with
reappearance of the same HPV type.
Occasionally the same HPV type will
reappear.
It is unclear whether this represents
reinfection or resurgence from a latent state
in the basal cells of the epithelium with very
low viral copy numbers and without late viral
expression
34. ►The longer a specific HPV type persists in
the epithelium, the lower the probability of
clearance within a defined period, and the
greater the risk of precancer
38. ► Only persistent high-risk HPV infection of the cervical epithelium appears to
trigger neoplastic progression.
The risk factors for HPV persistence and progression to CIN 3 are not fully
understood. HPV type is the strongest factor affecting risk of viral persistence .
HPV 16 is highly carcinogenic with an absolute risk of CIN 3 approaching 40% at
3 to 5 years .
The risks of progression to CIN 3 with other HPV types are several-fold lower.
Women infected with multiple HPV types have a further increased risk but it is
not clear if the risk is equal to or greater than the cumulative risk associated with
each of the individual HPV types.
It is also unknown whether infection with multiple HPV types interferes with
persistence of a given HPV type or with risk of progression to CIN 3 .
39. ►The modal time from HPV infection to CIN 3
is 7 to 15 years, with infection occurring in
the late teens or early twenties and CIN 3
diagnosis peaking at 25 to 30 years .
The average age of diagnosis of CIN 3
depends on average societal age of first
intercourse, a proxy for initial HPV
exposure, and age of onset and intensity of
screening
40. ►CIN 3 lesions are a homologous population
of aneuploid lesions, mostly associated with
oncogenic HPVs, and are genuine cancer
precursors.
►The transit time to invasive cancer is
variable, taking as little as 12 to 18 months
or as long as several decades. Most
cervical abnormalities do not transform to
invasive cancer
44. ► Cervical neoplasia can be viewed as the result of a complex interplay between
a “seed,” that is, high-risk HPV types, and a “soil,” that is, the immature,
metaplastic epithelium of the cervical transformation zone.
Exposure to specific high-risk HPV types, in the presence of cofactor activity,
may deviate the metaplastic process along a neoplastic pathway.
Disease expression begins at the new squamocolumnar junction. The initial
abnormality produced is usually a low-grade cervical lesion. Such lesions
represent a heterologous mixture of genuine cancer precursors and benign
HPV infections . The most critical step in cervical carcinogenesis is not
acquisition of an HPV infection but progression to CIN 3.
HPV infection alone is necessary but not sufficient to induce carcinoma in an
immunocompetent host.
HPV infection with oncogenic viral types is much more common than cervical
neoplasia, indicating the necessity of cofactors in the process of cervical
carcinogenesis .
45.
46.
47. Co-factor Interaction with Human
Papillomavirus
►Plausible cofactors in cervical and lower
genital tract carcinogenesis include the use
of tobacco products, infection by other
microbial agents, specific vitamin
deficiencies, hormonal influences, and
immunosuppression.
48. Cigerrate smoking
►Cigarette smoking has been demonstrated
to be a risk factor for cervical and vulvar
carcinoma.
An increased risk of developing a high-
grade squamous intraepithelial lesion
(HSIL) has been demonstrated among high-
risk HPV positive women who smoke or
who are passive smokers
49. ►Cigarette smoking influences epithelial
immunity by decreasing the numbers of
antigen-presenting Langerhans cells in the
genital epithelium .
Cervical HPV infection and CIN are
associated with diminished numbers of
intraepithelial Langerhans cells. Such local
immunologic depletion could favor viral
persistence, contributing to malignant
transformation
50. Infection by Other Microbial
Agents
► Genital HPV infection and cervical neoplasia are more
common among individuals who have had multiple sexual
partners or whose partner has had multiple sexual partners
.
An increased incidence of other sexually transmitted
diseases has been reported in association with genital HPV
infection and cervical neoplasia .
Disruption of epithelial integrity and reparative metaplasia
associated with acute cervicitis that is due to Chlamydia
trachomatis, Neisseria gonorrhoeae, herpes simplex virus
(HSV), or Trichomonas vaginalis may increase
susceptibility to genital HPV infection.
52. Sex Hormonal Influences
►Epidemiologic studies have shown an
increased risk of CIN in long-term oral
contraceptive pill (OCP) users, rising to
twofold for 5 or more years of OCP use.
OCP-induced folate deficiency with reduced
metabolism of mutagens is a proposed
mechanism for increased risk.
53. Exogenous and Endogenous
Immunosuppression
► The risk of CIN and cervical cancer is increased in human
immunodeficiency virus (HIV)-infected women, and failure
rates of treatment for preinvasive lesions are increased.
HPV prevalence and persistence are increased in HIV-
positive women.
Systemic immune suppression from diseases such as
Hodgkin's disease, leukemia, and collagen vascular
diseases are associated with an increased incidence and
recalcitrancy of HPV-associated disease.
54. MODES OF TRANSMISSION
► 1. Sexual transmission- Genital HPV infection are primarily through sexual
contact. Infectivity rate is approximately 65%.
The risk factors for transmision are:
- Number of lifetime sexual partners
-younger age group
-cigarette smoking
-use of oral contraceptive pills
2.Extragenital skin transmission: Skin to skin or genital to skin transmission
has been observed in periungal and congenital warts.
3.Formites: Transmission through formites is arare documentation, eg. Gloves,
surgical instruments.
4.Genital HPV types appear to be uncommonly transmitted in neonatal period.
The only clinically expressed HPV disease that is acquired at birth is laryngeal
papillomatosis. This is mainly caused by HPV-6 and 11.
55. HISTOLOGY
► Infected cells exhibit nuclear atypia. Koilocytosis ,
described as acombination of perinuclear halo with
pyknotic or shrunken nucleus is a charateristic feature of
papilloma virus infection .
► Other features include dyskeratosis, atypical basal cells,
acanthosis and multinucleation. Koilocytosis is the most
specific marker except in HPV-16 and 18 where it is often
absent.
56. CLINICAL FEATURES
► Infection with HPV disease presents with a wide variety of
clinical findings. The spectrum of HPV disease include:
1.SUBCLINICAL HPV INFECTED OF CERVIX ,
VAGINA, VULVA PERINEUM AND ANUS:
HPV trnamission also occurs in absence of lesion during
latent phase. Subclinical HPV infection may be 10 to 30
times more common than cytologically apparent
infections.Latent infection may persist;progress to clinical
disease or resolve.
57. ►2.GENITAL WARTS:
Genital warts can be divided into four morphological types:
a.Condyloma acuminata – They are cauliflower – shaped
warts usually present initially at forchette and adjacent labia, then
spread to other parts of vulva.
b.Papular warts- Dome shaped (usually skin coloured)
c.Keratotic genital warts- They are thick horny warts.
d.Flat-topped papules – May be present on cervix.
Morphological appearance of all warts involving different sites is
similar. External genital warts are frrequently multifocal (present as one
or more lesion at asingle anatomic site) or multicentric (present as one
or more lesion on different anatomic sites).
58. ►Condylomata acumlnata, also called genital
warts ,is induced by papillomavirus
►Pathogen:
Papillomavirus, has above 80 kinds of
antigens. Type 611404451 are
belong to low danger tpye and
►161831333539455556 are belong to high
danger tpye which have close relationship
with canceration
66
68. CLINICAL FEATURES
► LOWENSTIEN-BUSCHKE tumor or “giant
condylomata” are extremely large genital warts seen in
patient with impaired cell mediated immunity due to HIV ,
immuosuppressive therapy, lymphoma or pregnancy .
These lesions can become locally invasive and destructive
but do not metastasize and are usually infected by HPV-6
69. ►3. INTRAEPITHELIAL NEOPLASIA OF
CERVIX , VULVA , PERINEUM, VAGINA ,
PENIS AND ANUS: High risk HPV are found to be more
common cause of intraepithelial lesion. Lesions with
persistent HPV tend to progress more to invasive cancer.
►4. JUVENILE REPIRATORY (LARYNGEAL)
PAPILLOMATOSIS: In infants it is caused by HPV
-6 and HPV-11. The mode of tranmission is not
compeletely understood. Potential routes include
tranplacental, intrapartum in birth canal or postnatal. The
estimated risk of infection from infected mothers to
neonates ranges from 1 per 100 to 1 per 1000 cases.
70. DIAGNOSIS
1.Genital warts- They can be visualised by gross
inspection
2Subclinical HPV infection is diagnosed by
colposcopy.
After application of 3-5 percent acetic acid , subclinical
HPV has shiny- white colour with irregular borders and
satellite lesions.
Vaginal subclinical infection may exibit reverse punctation.
3Squamous intraepithelial lesion(SIL) of cervix:
They are detected mainly by routine cytological screening
test Paps smear.
71. HPV DETECTION
TECHNIQUES
► 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 in U.S
This cytology test has excellent specificity but only fair
sensitivity.
72. ►. In 1988, the first National Cancer Institute
(NCI) workshop held in Bethesda, Maryland,
Classification resulted in the development of
the Bethesda System for cytologic
reporting .
A standardized method of reporting cytology
findings was needed to facilitate peer review
and quality assurance. The terminology was
refined in the Bethesda III System (2001).
73.
74. ► Cellular changes associated with HPV (ie, koilocytosis and CIN 1) are
incorporated within the category of LSIL because the natural history,
distribution of various HPV types, and cytologic features of both of
these lesions are the same .
Long-term follow-up studies have shown that lesions properly
classified as koilocytosis progress to high-grade intraepithelial
neoplasia in 14% of cases and that lesions classified as mild dysplasia
progress to severe dysplasia or CIS in 16% of cases.
Thus, on the basis of clinical behavior, molecular biologic findings, and
morphologic features, HPV changes and CIN 1 appear to be the same
disease
75. ► The Pap test has been successful in reducing the incidence of cervical cancer
by 79% and the mortality by 70% since 1950 .
Unfortunately, 20% of women in the
United States do not undergo regular screening and have not had a Pap test in
the previous three years.
In three recent reviews of the accuracy of cervical cytology assessment, the
sensitivity of the Pap test in detecting CIN 2and3 ranged from 47% to 62% and
the specificity ranged from 60% to 95% .
Approximately 30% of new cancer cases each year result from women who
have undergone Pap testing, but errors of sampling, fixation, or interpretation
occur previous 3 years.
76. New Liquid Pap Tests
►More accurate test
▪ Thin, uniform layer of cells
▪ Screening errors reduced by half
►Screening needed less often
►Can test for HPV with same specimen if
abnormal cells found
►Expensive
77. COLPOSCOPY
►Colposcopy directed biopsies are often
considered 100 percent accurate.
This leads to the opinion that “gold
standard” for disease detection is
colposcopy.
78.
79.
80. ► Colposcopy is ideally suited to help accurately evaluate
lesion severity so that an appropriate treatment plan can be
instituted.
► Historically, most practitioners recommended colposcopy
for all women with Papanicolaou test findings of HGSIL or
worse.
► In 2001, the Bethesda conference provided consensus
guidelines for the evaluation of women with lower-grade
findings.
► This expert panel recommended that all women with LGSIL
or ASCH Papanicolaou test findings also undergo
colposcopy.
►
They further recommended that women with ASCUS
findings can be evaluated by colposcopy, repeat
Papanicolaou test, or HPV DNA analysis.
81. Women with ASCUS smears with negative HPV
testing were recommended to return to annual
Papanicolaou test screening.
These recommendations were based largely on
evidence-based information obtained from the
ASCUS-LSIL Triage Study (ALTS).
The data from this trial indicate that HPV triage in
patients with ASCUS is at least as sensitive as
colposcopy in detecting cervical intraepithelial
neoplasia (CIN) while concomitantly referring half as
many women to colposcopy.
Immediate HPV typing for ASCUS is now
recommended as the preferred triage by the American
Society for Colposcopy and Cervical Pathology.
82. A special circumstance not discussed in the ALTS trial
specifically is ASCUS management in postmenopausal
women with evidence of atrophy.
If a woman has no contraindication to estrogen therapy,
an acceptable option is a trial of intravaginal estrogen
therapy with repeat cytology 1 week after completion of
therapy.
It is also acceptable, however, to treat postmenopausal
women with ASCUS by performing HPV testing.
83. Finally, the ALTS trial also evaluated management of LSIL.
The data suggest that because of the risk of CIN and the
high prevalence of high-risk HPV types (more than 85%) in
LSIL cases, no efficient triage for LSIL exists.
Expedient colposcopy for LSIL is therefore indicated
because only a small percentage of patients would be
triaged differently if HPV DNA testing were performed.
84. NUCLEIC ACID DETECTION
TESTS
► As only certain types of HPV is primarily associated with cervical
cancer, HPV typing becomes nnecessary. The following nucleic acid-
based tests have been used for detecting and typing HPV in
specimens:
► 1.Polymerase chain reaction
2.Hybrid capture 2 procedure
3.In situ hybridisation technique
The median sensitivity of HPV testing for routine screening of women
with CIN2, CIN3 and cervical cancer is 93 % compared to 75 % for
Pap smear. Paps smear is slightly more specific than HPV DNA
testing when the presence of high grade cervical diesease is
considered.
ISH is less – sensitive than PCR or hc2 but is abetter confirmatory test.
85. ► INDICATIONS OF DNA TESTING
1.To aid the diagnosis of sexually transmitted HPV
infections.
►
2.To screen patients with ASCUS pap smear and
determine the need for colposcopy.
►
3.To aid risk assessment of women with LSIL or HSIL
before colposcopy.
►
HPV screening for all women is not recommended as it is
not cost effective.
86.
87. Human Papillomavirus Vaccine
Development
The development of a vaccine for HPV could lead to a
potential reduction in the incidence of cervical cancer and
its precursor lesions, other associated cancers (anal,
penile, vaginal, vulvar), and genital warts .
Recently three separate trials have been performed to test
the efficacy of various HPV vaccines.
Each trial was able to show that the vaccine they were
using was efficacious in preventing persistent HPV
infection
88. The quadrivalent HPV vaccine is currently licensed in over
80 countries and the bivalent vaccine in 2 countries.
Vaccination is approved for young women up to the age of
26 years.
The greatest public health benefit is achieved by
vaccination of girls and young women prior to sexual
initiation as the vaccines are prophylactic .
The U.S. Advisory Committee on Immunization Practices
(ACIP) recommends routine vaccination with the
quadrivalent HPV vaccine of all 11- to 12-year-old girls,
“catch-up” vaccination of all 13- to 26-year-old girls and
women
89. ► Vaccination of young sexually active women may still
provide some protection.
Routine performance of Pap smears or HPV DNA testing
prior to vaccination is not recommended, although such
screening may be appropriate for sexually active women.
Cervical cancer screening should continue for the
immunized population to screen for disease caused by
nonvaccine HPV types, to monitor the continued efficacy of
the vaccination program (which may not be 100%), and to
screen HPV infected women as the vaccine is not
therapeutic.
90. ► The optimal vaccine dosing schedule is three doses at 0, 2,
and 6 months. Accelerated delivery schedules over 4 months
are being used in some countries.
The U.S. Advisory Committee on Immunization Practices
(ACIP) recommends :
► First and second doses must be separated by at least 4
weeks.
► Second and third doses must be separated by at least 12
weeks.
► If the dosing schedule is interrupted, the vaccine series is not
restarted but the required dose is given as soon as possible.
91. Current HPVL1 VLP
vaccines
►
►
►
►
Two HPVL1VLP vaccines have been developed commercially
Both the vaccine development programmes began on the basis of the
discovery by several academic groups that the L1 coat protein of
papillomavirus could assemble into a virus like particle (VLP)
when expressed as a recombinant protein in a heterogeneous
eukaryotic system.
VLP are highly immunogenic and
VLP immunized individuals have made anti VLP antibody responses
substantially greater than that identified and natural infections.
92. ►HPV4 (Gardasil)
▪ contains types 16 and 18 (high risk) and types 6
and 11 (low risk)
►HPV2 (Cervarix)
▪ contains types 16 and 18 (high risk)
►Both vaccines are supplied as a liquid in a
single dose vial or syringe
►Neither vaccine contains an antibiotic or a
preservative
93. Composition of the HPV vaccine
►HPV – 16,18 plus/minus 6,11
►L1 protein VLPs from the capsid, no viral
DNA & hence non-infective
►Produced by recombinant DNA technology
►Adjuvant- ASO4 or simply Aluminium
hydroxide
94. Bivalent Human Papillomavirus
Vaccine
Cervarix composition- 1dose(0.5ml)
► HPV type 16 L1 protein -20µg
► HPV type 18L1 protein-20 µg
► Adjuvanted by ASO4 containing 500 µg
► MPL-monophosphoryl lipid-50 µg
► Adsorbed on aluminium hydroxide
► Bivalent recombinant vaccine
► 0, 1, 6-month dosing regimen
95. Adjuvant technology: AS04
►
►
►
Originating from the Latin word adjuvare, meaning “to help”
Adjuvants are added to a vaccine to improve the immune response to
the Antigens
AS04 consists of an immunostimulant - Monophosphoryl Lipid A (MPL)
►
►
Adsorbed onto aluminium hydroxide (Al(OH)3)
Cervarix® adjuvanted with AS04 has been shown to induce both high
and Sustained antibody levels compared to the same antigens
adjuvanted with aluminium hydroxide alone.
96. HUMAN PAPILLOMA VIRUS
VACCINES
►
►
HPV4 vaccine is approved for
▪ females 9 through 26 years of age for the prevention of cervical
cancers, precancers and genital warts
▪ males 9 through 26 years of age for the prevention of genital warts
HPV2 vaccine is approved for
▪ females 10 through 25 years of age for the prevention of cervical
cancers and precancers
▪ not approved for males or for the prevention of genital warts
97. ►Correct and consistent condom(male &
female)
use may have a protective effect
on HPV acquisition, reduce the
risk for HPV-associated diseases,
and mitigate the adverse
consequences of infection
with HPV.
98. HPV Vaccine Recommendations
► Recommended age for routine HPV vaccination is 11 or 12
years
► Vaccination is recommended for females 13 through 26
years of age not previously vaccinated or who have not
completed the full 3-dose series
► The 3 dose series of HPV4 may be administered to males
9 through 26 years of age to reduce their likelihood of
acquiring genital warts
99. HPV Vaccine Special Situations
► Females 26 years of age or younger with equivocal or
abnormal Pap test, positive HPV DNA, or genital warts
may be vaccinated
▪ vaccine will have no effect on existing disease or
infection
► Females 26 years of age or younger who are lactating and
breastfeeding, or are immunocompromised may be
vaccinated
► Vaccination not recommended for pregnant women
▪ pregnancy testing is not needed before vaccination
102. HPV Vaccine and Cervical
Cancer Screening
► Cervical cancer screening recommendations have NOT
changed for females who receive HPV vaccine
► Females who are vaccinated could subsequently be
infected with a high-risk HPV type not in either vaccine
► Females who were sexually active prior to vaccination
could have been infected with a vaccine-type HPV before
vaccination
► Healthcare providers who administer HPV vaccine should
educate women about the importance of cervical cancer
screening
103. HPV TREATMENT
►
►
►
►
Genital warts can be treated by
a doctor and by different
methods.
Podofilox gel: A patient-
applied treatment for external
genital warts.
Imiquimod cream: A patient-
applied treatment.
Chemical treatments (including
trichloracetic acid and
podophyllin), which must be
applied by a trained health care
provider to destroy warts.
►
►
►
►
►
Cryotherapy: Uses liquid
nitrogen to freeze off the warts.
Laser therapy: Uses a laser
beam or intense lights to
destroy the warts.
Electrosurgery: Uses and
electric current to burn off the
warts.
Surgery: Can cut away the
wart in one office visit .
Interferon: an antiviral drug,
which can be injected directly
into warts.
104. CURE
►There is currently no cure for human
papillomavirus.
►Once an individual is infected, he or she
carries the virus for life even if genital warts
are removed.
►The development of a vaccine against HPV
is under way, but is still not available.
►If left untreated, some genital warts may
regress on their own.
105. HPV Vaccine And Male
►Like adolescent girls Poly valant HPV
vaccine should be advised to boys between
the age of 13-22 years of age before the
indulge in any sexual activity.
►It will help in controlling genital warts ,
anorectal cancer and cervical cancer intheir
life partner.
