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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
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
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
VAGINA
UTERUS
REVIEW OF CERVICAL ANATOMY
ENDOCERVICAL GLANDS
SQUAMOUS EPITHELIUM
OSCJ
SQUAMOUS EPITHELIUM
OSCJ
COLUMNAREPITHELIUM
OSCJ
COLUMNAR EPITHELIUM
SQUAMOUS EPITHELIUM
CERVICAL EVERSION(ECTROPION)
OSCJ
COLUMNAREPITHELIUM
NSCJ
TRANSFORMATION ZONE
SCCA:80-90%
Adenocarcinoma:10-20%
TRANSFORMATION ZONE
SQUAMOUS EPITHELIUM
BASEMENT MEMBRANE
GLANDULAR EPITHELIUM
STROMA
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
∏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
∏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
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.
SCREENING: The Pap smear
CIN 1
CIN 2
CIN 3
MICA
InvasiveCA
GLANDULAREPITHELIUM
STROMABASEMENT MEMBRANE
SQUAMOUSEPITHELIUM
TRANSFORMATION ZONE
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
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
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?
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?
ETIOLOGY∏Undoubtedly related to HPV
p53
Rb
E6E7
VIRUS HOST
§ HPV subtypes 16, 18, 31, 33, 35, 45, 51, 58, 59, 68
E6
E7
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
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!
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
DIAGNOSIS∏Abnormal Pap result without a gross lesion need colposcopic evaluation.
∏Gross cervical lesions should undergosimple cervical biopsy of the tumor.
colposcopy
biopsy
SCREENING: Colposcopy
biopsy tip
SCREENING: Colposcopy
SCREENING: Colposcopy
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.
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.
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
DIAGNOSIS: Conization∏Indications for conization or LEEP:
Mۀ MICA found on directed biopsy
Mۀ endocervical curettings showing intraepithelial neoplasia
DIAGNOSIS: Conization
DIAGNOSIS: Conization
GLANDULAREPITHELIUM
STROMA
SQUAMOUSEPITHELIUM
TRANSFORMATION ZONE
BASEMENT MEMBRANE
HISTOLOGIC TYPES
∏Squamous cell carcinomaMۀ large cell type§ keratinizing § non-keratinizingMۀ small cell type
∏Adenocarcinoma Mۀ endometrioid typeMۀ clear cell typeMۀ verrucousMۀ adenosquamous
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
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)
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
STAGING: FIGO classification (1998)
Ib1 Ib2
> Ia2< 4cm
> 4cmStage I
STAGING: FIGO classification (1998)
IIa IIb
Stage II
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.
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
TREATMENT∏Destructive methods for CIN lesions:
Mۀ electrocautery Mۀ cryosurgeryMۀ CO2 laser vaporization
Mۀ LEEP
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
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
TREATMENT∏Chemotherapy:
Mۀ adjuvant
Mۀ neoadjuvant
Mۀ concurrent
Mۀ indications
Mۀ current trends
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
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
TREATMENT∏Complications of treatment modalities:
Mۀ hemorrhage
Mۀ infection/sepsis
Mۀ incontinence
Mۀ fistula formation
Mۀ post-radiation fibrosis and scarring
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?
∏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
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
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.
FOLLOW-UP
∏Cytologic monitoring of recurrence
∏Regular survey for metastatic disease
∏Disease-free interval versus Cure
∏Palliative treatment for persistent
progressive disease
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.
SUMMARY…
∏Biopsy is essential in establishing the
diagnosis:Mۀ with guidance: Lugol’s solution, acetic acid
Mۀ colposcopy
Mۀ conization
Mۀ simple punch biopsy
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.