Transcript Cervical Disease and Neoplasms

Cervical Disease
and Neoplasms
Maria Horvat, MD, FACOG
Cervical Disease – Risk factors
HPV
Smoking – 2 fold increase
Young age at 1st coitus
Multiple sexual partners
A partner with multiple sexual partners
High parity
Lower socioeconomic status
Young age at 1st pregnancy
HPV in the United States
Cervical Disease
HPV associated with 99.7% of all
cervical cancer
HPV types associated with higher
oncogenic risk:
16, 18
31, 33, 35
45
51, 56
HPV – high risk types
HPV Infection in histologically confirmed
squamous cell carcinoma
70%
60%
59%
50%
40%
30%
20%
12%
10%
5%
4%
3%
HPV 45
HPV 31
HPV 33
0%
HPV 16
HPV 18
HPV
Obligatory intra-nuclear virus
Most remit spontaneously
5% of infected women have persistent
infection
PAP test
Only a screening test
Goal:
To prevent cervical cancer
Histology of (SIL)
squamous intraepithelial lesions.
Grade 1 = CIN 1; Grade 2 = CIN 2; Grade 3 = CIN 3
Cervical Neoplasia
Potential Co-Factors in Cervical
Carcinogenesis
Other infectious agents
Herpes
Chlamydia
HIV and other immunosuppression
Diet
Smoking
Hormonal contraceptives
Weak immunomodulatory effect
Eversion of columnar epithelium
Decrease in blood folate levels
Progesterone effect on HPV
Management of Adolescent Women
(<18 yrs) with histological diagnosis of
CIN – Grade 1
< 18 yrs old with CIN 1
Repeat Cytology at 12 mos
< HSIL
> HSIL
Repeat Cytology at 12 mos
Negative
Routine Screening
> ASC
Colposcopy
Management of Adolescent women
(<18 yrs) with histological diagnosis of
CIN – grade 2,3
<18 yrs old with CIN 2,3
Either treatment or observation is acceptable, provided colposcopy is satisfactory.
When CIN 2 is specified, observation is preferred. When CIN 3 is specified, or colposcopy is unsatisfactory, treatment is recommended.
Observation
OR
With colposcopy and cytology
at 6 mos intervals for 24 mos
2x negative cytology
And normal colpo.
Routine Screening
Treatment
with excision or
ablation of T-zone
colposcopy worsens or
High-grade cytology or
colpo. Persists for 1 yr.
Repeat Biopsy
Recommended
CIN 3, or CIN 2 that persists
for 24 mos since initial dx
Management of Women with
Atypical Squamous Cells: Cannot
exclude high grade SIL
(ASC – H)
>20 yrs old with ASC-H
Coloposcopic Examination
Management of Women with Atypical
Squamous cells of undetermined
significance - ASC-US
>20 yrs old with ASC-US
Repeat Cytology
@ 4-6 mos
Negative
Repeat
@ 4-6 mos
HPV DNA testing
>ASC
Positive
Negative
(for high risk type)
Colposcopy
Repeat cytol.
@ 12 mos
Naming
Cervical Intraepithelial Neoplasia
Biopsy Regress Persist Progress Progress
Result
to CIS
to
invasion
CIN 1
57%
32%
11%
1%
CIN 2
43%
35%
22%
5%
CIN 3
32%
<56%
-----
>12%
Colposcopic Grading
Low Grade
High Grade
Acetowhite Epithelium
Shiny or snow white, semitransparent
Dull, oyster white
Surface
Flat
Flat or irregular contour
Demarcation
Diffuse, irregular, flocculated, feathered
Internal demarcation line absent
Sharp, straight line
Internal demarcation line may be present
Vessels
Fine, with regular shapes, uniform caliber, normal
aborization pattern
Punctation or mosaicism associated with coarse,
dilated vessels with increased intercapillary
distance; bizarre vessels without aborization,
commas, hockey sticks, corkscrews, sharp bends
Iodine
Yellow, or variegated brown
Mustard yellow, yellow or iodine negative
Summary for the non-gynecologist
ASCUS
Negative
Repeat Pap
in 6 mos
HPV type
Positive
Refer for
coloposcopy
CIN 1 – mild dysplasia
< 18 yrs old
Repeat Pap
>18 yrs old
Colposcopy
CIN 2,3
Colposcopy
Confirmed CIN 2,3
Excision
(adolescents may perform colposcopy q 6 mos up to 24 mos)
Interventional Techniques Excisional
Conization
Cone of tissue is excised for further examination and/or to
remove a lesion
Tissue is usually stained with iodine to demarcate the area of
resection
Cold knife
Laser
LEEP
Loop electrosurgical excision procedure
May be complicated by burn artifacts
Ablative
Cryotherapy
Use of a probe containing carbon dioxide or nitrous oxide to freeze
the entire transformation zone and area or the lesion
Laser vaporization therapy
Atypical Glandular Cells
AGUS
Colposcopy
ECC
Endometrial Sample, women >35 yrs
What is colposcopy?
Cervical Cancer – staging review
Stage 0: CIS, CIN grade III
Stage 1: carcinoma strictly confined to the cervix
Stage 2: cervical carcinoma invades beyond the
uterus, but not to the pelvic wall or to the lower
third of the vagina
Stage 3: carcinoma has extended to the pelvic
wall. On rectal exam there is no cancer-free
space between the tumor and the pelvic wall. The
tumor involves the lower 1/3 of the vagina. All
cases with hydronephrosis or non-functioning
kidney unless known to be due to other causes.
Stage 4: Carcinoma has extended beyond the
true pelvis, or has involved the mucosa of the
bladder or rectum.
Cervical Cancer Staging
Stage 0: The cancer cells are very
superficial (only affecting the surface)
are found only in the layer of cells
lining the cervix, and they have not
grown into (invaded) deeper tissues
of the cervix. This stage is also called
carcinoma in situ (CIS) or cervical
intraepithelial neoplasis (CIN) grade
III.
Cervical Cancer Staging
Stage I: In this stage the cancer has invaded the cervix, but it has
not spread anywhere else.
Stage IA: This is the earliest form of stage I. There is a very small
amount of cancer, and it can be seen only under a microscope.
Stage IA1: The area of invasion is less than 3 mm (about 1/8-inch)
deep and less than 7 mm (about 1/4-inch) wide.
Stage IA2: The area of invasion is between 3 mm and 5 mm (about
1/5-inch) deep and less than 7 mm (about 1/4-inch) wide.
Stage IB: This stage includes Stage I cancers that can be seen
without a microscope. This stage also includes cancers that can
only be seen with a microscope if they have spread deeper than 5
mm (about 1/5 inch) into connective tissue of the cervix or are wider
than 7 mm.
Stage IB1: The cancer can be seen but it is not larger than 4 cm
(about 1 3/5 inches).
Stage IB2: The cancer can be seen and is larger than 4 cm
Cervical Cancer Staging
Stage II: In this stage, the cancer has
grown beyond the cervix and uterus, but
hasn't spread to the walls of the pelvis or
the lower part of the vagina.
Stage IIA: The cancer has not spread into
the tissues next to the cervix (called the
parametria). The cancer may have grown
into the upper part of the vagina.
Stage IIB: The cancer has spread into the
tissues next to the cervix
Cervical Cancer Staging
Stage III: The cancer has spread to the
lower part of the vagina or the pelvic wall.
The cancer may be blocking the ureters
(tubes that carry urine from the kidneys to
the bladder).
Stage IIIA: The cancer has spread to the
lower third of the vagina but not to the
pelvic wall.
Stage IIIB: The cancer has grown into the
pelvic wall. If the tumor has blocked the
ureters (a condition called hydronephrosis)
it is also a stage IIIB.
Cervical Cancer Staging
Stage IV: This is the most advanced stage
of cervical cancer. The cancer has spread
to nearby organs or other parts of the body.
Stage IVA: The cancer has spread to the
bladder or rectum, which are organs close
to the cervix.
Stage IVB: The cancer has spread to
distant organs beyond the pelvic area,
such as the lungs.
Question #1.
What if HGSIL pap and normal
colposcopy?
Answer #1.
LEEP or cone biopsy.
Question #2.
Biopsy on face cervix is normal and
ECC is positive, what is the next
step?
Answer #2.
LEEP or cone biopsy.
There is hope!
Gardisil immunization guards against
types 6, 11, 16, and 18.
Administer at 0, 2, and 6 months for
females 9 years or older.
HPV Vaccine Trials
Phase 2 Trial of Quadrivalent HPV Vaccine: Per Protocol
Efficacy
100%
100%
90%
89%
90%
% Vaccine Efficacy
80%
70%
60%
50%
40%
30%
20%
10%
0%
Persistant Infection
Reduction
HPV - Related disease Overall vaccine efficacy
reduced
Phase 2 Trial of Quadrivalent HPV
Vaccine: Conclusions
The vaccine was highly effective in
reducing incidence of persistent HPV
infection
Efficacy with regard to clinical disease
associated with HPV types 6,11,16,18, was
100%
The vaccine was highly immunogenic,
inducing high antibody titers to each HPV
type
The vaccine was generally well tolerated
Do condoms help prevent?
YES!
60% decrease in transmission
Does not eliminate risk.
Pap smear schedules:
Many different recommendations
ACOG
APGO
ACS
Pap smear recommendations
1st pap by age 21 or within 3 years of
1st coitus
Annually until the age of 30
Pap with HPV at age 30, then can
perform every few years.
Pap smear recommendations:
Post Menopausal
Some guidelines: No Pap
ACOG: q 3-5 years
Hysterectomized female:
If hysterectomy for benign reasons, then pap q
3-5 years
Yearly if:
–
–
–
–
–
–
Cervix present
History of abnormal paps
History of gyne cancer
History of DES exposure
History of cervical cancer
Smoking (increases chance of vaginal cancer)
References
APGO Educational Series on Women’s
Health Issues: Advances in the Screening,
Diagnosis, and Treatment of Cervical
Disease
Review in Obstetrics and Gynecology, Vol.
1 No. 1 2008
American Society for Colposcopy and
Cervical Pathology
Crosstalk; Preventing Cervical Cancer and
Other Human Papillomavirus-related
diseases