pre-malignant & malignant diseases of the cervix jose b. moran, md assistant professor iii...
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PRE-MALIGNANT & MALIGNANT DISEASES of the CERVIX
Jose B. Moran, MDAssistant Professor IIIDepartment of Obstetrics and GynecologySection of Gynecologic OncologySt. Luke’s College of Medicine-W.H. Quasha Memorial
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Highlights of the discussion:∏Brief review of cervical anatomy§ formation of the transformation zone§ histology of the cervical epithelium
∏Epidemiology § role of HPV infection§ risk factors
∏Screening and the role of Pap smear§ present recommendations
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Highlights of discussion:∏Premalignant lesions§ symptoms & classification§ diagnosis & treatment
∏Malignant/Invasive lesions§ symptoms§ diagnosis and staging classification§ treatment and its complications§ prognostic factors & follow-up
∏Preventive measures: Gardasil, Cervarix
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VAGINA
UTERUS
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REVIEW OF CERVICAL ANATOMY
ENDOCERVICAL GLANDS
SQUAMOUS EPITHELIUM
OSCJ
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SQUAMOUS EPITHELIUM
OSCJ
COLUMNAREPITHELIUM
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OSCJ
COLUMNAR EPITHELIUM
SQUAMOUS EPITHELIUM
CERVICAL EVERSION(ECTROPION)
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OSCJ
COLUMNAREPITHELIUM
NSCJ
TRANSFORMATION ZONE
SCCA:80-90%
Adenocarcinoma:10-20%
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TRANSFORMATION ZONE
SQUAMOUS EPITHELIUM
BASEMENT MEMBRANE
GLANDULAR EPITHELIUM
STROMA
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EPIDEMIOLOGY∏most common gynecologic cancer in developing countries.
∏third most common gynecologic
cancer in developed countries.
∏400,000 women affected: third most common cancer in women worldwide
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∏Affects women 44-55 years old.
∏current trend towards the younger age group being affected.
∏Runs an indolent course starting on thesurface layer of the cervix.
EPIDEMIOLOGY
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∏A pre-cancerous phase (dysplasia, CIN) may gradually progress into cancer.
∏Dysplasia is 100% curable, often withoutthe need for hysterectomy.
∏Cervical cancer is preventable!!!
EPIDEMIOLOGY
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SCREENING: The Pap smear
∏based on the concept that cervical cancer is the endpoint of a continuum
∏The whole spectrum may be found within one cervix.
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SCREENING: The Pap smear
CIN 1
CIN 2
CIN 3
MICA
InvasiveCA
GLANDULAREPITHELIUM
STROMABASEMENT MEMBRANE
SQUAMOUSEPITHELIUM
TRANSFORMATION ZONE
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SCREENING: The Pap smear
GRADE TRANSIT TIME PROGRESSION
CIN 1-2 7 yrs to CIS 50%
CIN 3
MICA
7-10 yrs to MICA 66%
100%2 yrs to invasive CA
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SCREENING: The Pap smear
∏Simple, painless screening test
∏Sample exfoliation taken from the transformation zone
∏It is the most powerful tool in a woman’s arsenal to prevent cervical cancer.§ cost-effective§ high specificity§ high sensitivity
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SCREENING: The Pap smear∏If every woman would submit herself to it annually, the incidence would dramatically drop or would nearly be eliminated.
∏At what age do you start?
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SCREENING: The Pap smear∏Recommendations of the ACOG:
Mۀ starts when a woman become sexually active or reach the age of 18 years
Mۀ done annually but less frequently after 2-3negative smears, if low risk
Mۀ should be done no less than annually for those considered at risk
∏Who are considered at risk?
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ETIOLOGY∏Undoubtedly related to HPV
p53
Rb
E6E7
VIRUS HOST
§ HPV subtypes 16, 18, 31, 33, 35, 45, 51, 58, 59, 68
E6
E7
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ETIOLOGY∏Common Risk FactorsMۀ young age at coitarcheMۀ multiple sexual partnersMۀ sex with high-risk malesMۀ history of sexually-transmitted diseasesMۀ smokingMۀ low socio-economic statusMۀ immunodeficient states•whole-organ transplantation•Hodgkin’s disease•HIV-AIDS
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SCREENING: The Pap smear
∏Your role as responsible healthcare givers
is not only to diagnose and treat diseases
but more importantly to prevent it by
proper EDUCATION!
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SIGNS & SYMPTOMS∏Early symptoms:
Mۀ vaginal dischargeMۀ unexpected coital bleedingMۀ abnormal vaginal bleeding
∏Late symptoms:
Mۀ pain in the pelvic areaMۀ unpleasant vaginal dischargeMۀ heavy vaginal bleedingMۀ pedal edema/uremia
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DIAGNOSIS∏Abnormal Pap result without a gross lesion need colposcopic evaluation.
∏Gross cervical lesions should undergosimple cervical biopsy of the tumor.
colposcopy
biopsy
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SCREENING: Colposcopy
biopsy tip
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SCREENING: Colposcopy
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SCREENING: Colposcopy
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DIAGNOSIS: Guidelines
∏Patients with colposcopically identified abnormal epithelium should undergo biopsy and endocervical curettage.
∏A conization or loop electrosurgical excisionis sometimes needed for a more accurate diagnosis.
∏Abnormal Pap result without a gross lesion need colposcopic evaluation.
∏Gross cervical lesions should undergosimple cervical biopsy of the tumor.
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DIAGNOSIS: Conization∏The premise is that:
Mۀ conclusive microscopic diagnosis cannot be made based on the tissue submitted.
Mۀ the tissue previously submitted has alarming features of a possible more serious disease.
∏The purpose is to obtain adequate amount of tissue for conclusive microscopic diagnosis.
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DIAGNOSIS: Conization∏Indications for conization or LEEP:
Mۀ colposcopically directed biopsy does not adequately explain abnormal cells on Pap.
Mۀ atypical epithelium extends into the endocervical canal (unsatisfactory colposcopy)
Mۀ abnormal cytologic findings with no visible colposcopic lesion
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DIAGNOSIS: Conization∏Indications for conization or LEEP:
Mۀ MICA found on directed biopsy
Mۀ endocervical curettings showing intraepithelial neoplasia
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DIAGNOSIS: Conization
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DIAGNOSIS: Conization
GLANDULAREPITHELIUM
STROMA
SQUAMOUSEPITHELIUM
TRANSFORMATION ZONE
BASEMENT MEMBRANE
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HISTOLOGIC TYPES
∏Squamous cell carcinomaMۀ large cell type§ keratinizing § non-keratinizingMۀ small cell type
∏Adenocarcinoma Mۀ endometrioid typeMۀ clear cell typeMۀ verrucousMۀ adenosquamous
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STAGING
∏Primarily done by palpation & inspectionof the cervix, vagina, parametrium andpelvic side walls
Mۀ extrapelvic areas such as supraclavicular nodes
∏Extent of the disease should be determined:
Mۀ chest X-ray
Mۀ cystoscopy
Mۀ sigmoidoscopy
Mۀ bone survey
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STAGING
∏Newer imaging technology may be useful to determine the extent of the disease and assist in treatment planning, but they are not considered by FIGO as tools for staging:
Mۀ lymphangiography
Mۀ computerized tomography (CT scan)
Mۀ magnetic resonance imaging (MRI)
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STAGING: FIGO classification (1998)
∏Stage 0Mۀ carcinoma-in-situ∏Stage I: tumor confined to the cervix.
Extension to the corpus is disregarded. Mۀ Stage Ia: MICA*1
§ Ia1: minimal microscopically evident stromal invasion.§ Ia2: depth of invasion <3mm plushorizontal spread < 7mm
*conization is ideally required1lymphvascular space involvement should be indicated but does not change the stage
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STAGING: FIGO classification (1998)
Ib1 Ib2
> Ia2< 4cm
> 4cmStage I
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STAGING: FIGO classification (1998)
IIa IIb
Stage II
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STAGING: FIGO classification (1998)
IIIa IIIb
Stage III*
*All cases with hydronephrosis or non-functioning kidney are included unless they are known to be due to other causes.
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STAGING: FIGO classification (1998)
∏Stage IV: tumor has extended beyond the true pelvis or has clinically involved the bladder* or rectum.(*bullous edema is not assigned Stage IV)
Mۀ Stage IVa: spread to adjacent organs
Mۀ Stage IVb: spread to distant organs
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TREATMENT∏Destructive methods for CIN lesions:
Mۀ electrocautery Mۀ cryosurgeryMۀ CO2 laser vaporization
Mۀ LEEP
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TREATMENT
∏Criteria for destructive methods:
Mۀ colposcopy is satisfactoryMۀ endocervix is free Mۀ conization is not indicatedMۀ invasive cancer is ruled outMۀ cytologic, colposcopic, and histologic evaluations correlate
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TREATMENT∏Surgery: Radical hysterectomyMۀ good candidates: young, healthy Mۀ allowable for up to stage IIa onlyMۀ small lesions (less than 4 cm) Mۀ advantage over radiation: assessment, sexual function preservation
∏Radiotherapy
Mۀ can be used for all stages Mۀ It is the treatment of choice in an ideal setting
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TREATMENT∏Chemotherapy:
Mۀ adjuvant
Mۀ neoadjuvant
Mۀ concurrent
Mۀ indications
Mۀ current trends
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TREATMENTAbnormal Pap smear
Colposcopicevaluation
NOYESRepeat
Pap smear
Destructive Methods• Chemical cautery• Electrocautery • Cryotherapy• Diathermy/LEEP • Vaporization
Fertilitypreservation
desired
YES
NO
• CIN I• CIN II• CIN III
TAH
• Normal
Conization MICA
Findingssignificant
• MICA
Biopsy & ECC
• Margins clear• No lymph vascular space involvement• Follow-up assured• Completion surgery later • Complications:-bleeding (2 wks)-stenosis (6 mos)
Invasive CA
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CHEMOTHERAPY
TREATMENT
Major advantage:• applicable for all stages
Major advantage:• preservation of the ovaries• preservation of vagina
St. Ib to IIa
lesion < 4 cm
lesion > 4 cm
Radical HysterectomyPelvic lymphadenectomy
good surgical risk
Radiotherapy• external beam• intracavitary
CHEMOTHERAPY
deep stromal invasion lymph node (+)
YES
NO
Stage IIb & higher
• young patient• poor histology• bulky lesions
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TREATMENT∏Complications of treatment modalities:
Mۀ hemorrhage
Mۀ infection/sepsis
Mۀ incontinence
Mۀ fistula formation
Mۀ post-radiation fibrosis and scarring
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Cervical cancer coexistent with pregnancyCervical cancer coexistent with pregnancy
∏Difficulty and ease in diagnosis∏Limitations of some procedures: ECC and
conization∏Definitive treatment for CIN is postponed
until after puerperium.∏Is the prognosis worse if the disease is
associated with pregnancy?
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∏The AOG is the primary consideration in treating invasive lesions associated with pregnancy:Mۀ less than 20 weeks, manage as if notpregnant.Mۀ beyond 20 weeks, wait until fetal viabilityMۀ ethical considerations
Cervical cancer coexistent with pregnancyCervical cancer coexistent with pregnancy
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PROGNOSTIC FACTORS
∏Age at diagnosis∏Stage of the disease∏Histologic type∏Size of the tumor∏Depth of stromal invasion∏Status of the regional nodes∏Attending medical problems
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FOLLOW-UP
∏The risk of recurrence is highest during the first year after treatment, but wanes thereafter.∏Metastasis can occur in any organ but more commonly in the central pelvis, bones, lungs and liver.∏Cases can be classified as cured after a disease-free interval of 5 years.
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FOLLOW-UP
∏Cytologic monitoring of recurrence
∏Regular survey for metastatic disease
∏Disease-free interval versus Cure
∏Palliative treatment for persistent
progressive disease
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SUMMARY
∏Cervical cancer is a preventable disease.
∏Pap smear is the most cost-effective
screening tool.
∏Human Papilloma Virus infection is a
major risk factor in its genesis.
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SUMMARY…
∏Biopsy is essential in establishing the
diagnosis:Mۀ with guidance: Lugol’s solution, acetic acid
Mۀ colposcopy
Mۀ conization
Mۀ simple punch biopsy
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SUMMARY
∏MICA requires a cone biopsy.
∏Treatment and prognosis are largely
dependent on the extent of the disease
Mۀ Conservative treatment for premalignant
Mۀ Radiotherapy
Mۀ Radical surgery
∏Uremia is the most common form of
exit.
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