Carcinoma cervix Premanagement

By-Dr Satyajeet Rath

Topics Covered• Clinical Presentation• Examination• Diagnostic Work up• Staging

Clinical Presentation• Asymptomatic - Most common presentation in western

countries due high rate of screening• Intraepithelial or early invasive carcinoma of the cervix may

be detected by cytological smears before symptoms appear• Abnormal vaginal bleeding– earliest symptom of invasive

cervical cancer (most commonly post coital bleeding)• Metrorrahgia – Inter menstrual bleeding• Menorrhagia – Heavier than usual flow • Fowl smelling discharge – May or may not be mixed with

blood• Exophytic/ulceroproliferative mass visible on examination

Symptoms of Advanced Carcinoma Cervix

• Anemia,Fatigue – Due to chronic blood loss • Bowel obstruction —vomiting , abdominal pain and

distention• Anuria -- Renal failure – due to pressure effect on

ureter leading to back pressure on kidney• Rectal bleeding- venous engorgement due to

pressure effect• Constipation• Dysuria

Contd…• Hematuria• Persistent edema of lower limb – Obstruction of

lymphatic channel from lower limb

• Pelvic pain-• Flank or leg pain – Both may be due to Associated with pelvic inflammatory disease Para aortic lymph node involvement lumbosacral root involvement Hydroureteronephrosis

Contd… Ascites- Due to peritoneal deposits Dribbling of urine per vaginum –Due to vesico vaginal fistula formation Fecal matter per vaginum- Rectovaginal fistula

• Metastasis as Cervical Malignancy • Metastasis of distant tumors to the uterine cervix is rare

(about 4% of all tumors) and should be considered in the differential diagnosis.

• Metastases to the cervix from the breast, ovary, and kidney have been reported.

WHO histological classification of tumours of the uterine cervix.

• epithelial tumours• squamous tumours and precursors• glandular tumours and precursors • others

• mesenchymal tumours and tumour-like conditions

• mixed epithelial and mesenchymal tumours

• melanocytic tumours • miscellaneous tumours • lymphoid and haematopoetic• secondary tumours

Histologic Subtypes• Squamous-Cell Carcinoma(>90%)

• Large cell-Keratinizing or Nonkeratinizing or small cell carcinomas

• Verrucous-• very well differentiated scc, tendency to recur locally

but not metastasize• Papillary transitional• Lymphoepithelioma-like

• Adenocarcinoma (7-10%)• (arises from the cylindrical mucosa of the

endocervix or the mucus secreting endocervical glands

• Mucinous• Endometrioid- MC Endocervical adeno ca• Clear Cell• Serous• Mesonephric• Well differentiated villoglandular• Minimal deviation (adenoma malignum)-

associated with Peutz-Jeghers,ominous natural history

• Other epithelial• Adenosquamous• Glassy Cell• Carcinoid Tumor• Neuroendocrine• Small-cell• Undifferentiated• Basaloid Ca• Primary Sarcoma of cervix

• Cervical malignant Mixed Mullerian Tumours, compared to their counterparts are confined at presentation and better prognosis.

• DIAGNOSTIC WORKUP FOR CARCINOMA OF THE UTERINE CERVIX

Patterns of Spread• Local Invasion• Lymphatic

• Risk relates to depth of invasion• Pelvic nodes before paraaortic or supraclavicular

• Hematogenous• More likely in adenocarcinoma, neuroendocrine or small

cell tumors• Intraperitoneal

• Unknown incidence• Poor prognosis

Patterns of Lymphatic Spread

Distribution of pelvic node metastases in 14 patients with stages IB to IIA cervical cancer, tumor size <4 cm (A), and 38 patients with locally advanced cervical cancer treated with neoadjuvant chemotherapy (B). (From Benedetti-Panici P, Maneschi F, Scambia G, et al. Lymphatic spread of cervical cancer: an anatomical and pathological study based on 225 radical hysterectomies with systematic pelvic and aortic lymphadenectomy.

Incidence of pelvic lymph node mets

Leibel and Philips,Textbook of Radiation Oncology, 3rd Edition

The most commonly involved groups were the parametrial, obturator, external iliac, and common iliac nodes.

• CARCINOMA OF THE UTERINE CERVIX (MALLINCKRODT INSTITUTE OF RADIOLOGY 1959–1986): ANATOMIC SITE OF FIRST METASTASIS

• Bone metastases occurred in 16% of patients, most commonly to the lumbar and thoracic spine.

Thorough History & Examination

Pretreatment Evaluation• HISTORY-

--Age --Menstrual status –Pre or post menopausal Menstrual frequency Amount, Duration Associated pain Post Coital Bleed --Early Age of onset of sexual activity --Promiscuity --Multiple sexual partners --Associated comorbidity – DM , HTN --Addiction history- smoking --Long term OCP use --IUD use --having multiple full term pregnancies --younger than 17 at 1st full term pregnancy --DES use --Family History of cervical cancer

Contd…-- Discharge per vaginum- Amount Duration Nature – serous or serosanguinous Odour – fowl smelling or not -- Pain – Site ,Intensity ,Radiating to any part-- Pain during intercourse.-- Swelling of lower limb-- Dribbling of urine per vaginum or fecal matter through vagina--immunosuppression – HIV AIDS HPV Infection is the most important risk factor

Examination

There are three steps:

1. The External Genital Exam2. The Speculum Exam3. The Bimanual Exam

Prerequisites :

• Patient must be counselled properly regarding the procedures to be done.• A female attendant should be present by the side(nurse/or relative).• A light source should be available.• Sterile gloves,swabs,speculum,sponge holding forceps required.

1.Shaws’s Gynaecology,The gynaecology examination2.Dutta’s Textbook of Gyanecology5th edition

Step 1. The External Genital Exam • Visually examine the soft folds of the vulva and the opening of

the vagina to check for signs of irritation, discharge, cysts, genital warts, or other conditions.

• Note character of visible vaginal discharge if any.

• Elicit the signs of Stress incontinence and Genital prolapse.

• Look for hemorrhoids,any other palpable pathology over the area.

Step 2. The Speculum Exam • Speculum examination

should preferably be done prior to bimanual examination.

• Advantages : • Cervical scrape

cytology and endocervical sampling can be taken as screening in the same sitting.

• Discharge P/V can be sent for examination if need be

• Cervical lesion may bleed during bimanual examination which makes the lesion difficult to visualise • Anterior vaginal wall is to be visualized by Sim’s

speculum

Step 2. The Speculum Exam • Insert a speculum into the vagina

usually in lithotomy position .• When opened, it separates the

anterior and posterior lip of the vagina, which normally are closed and touch each other, so that the cervix can be seen.

• Patient may feel some degree of pressure or mild discomfort when the speculum is inserted and opened.

• Will likely feel more discomfort if tensed or if vagina or pelvic organs are infected so it is essential that patient must be advised to relax

Contd..

• The position of the cervix or uterus may affect the comfort as well.

• May feel the chill of the metal, if a metal speculum is used

• Lubricate the speculum and warm it to body temperature for more comfort.

PER SPECULUM

BIMANUAL DIGITAL EXAMINATION1) Assessing the cervix:Vaginal fingers locate the cervix and the

external cervical os:- Determine whether it is open or closed- Directed posteriorly when the uterus is

anteverted- Consistency

- usually firm when normal, - but hard due to fibrosis or carcinoma, - soft in pregnancy

- Note any mass its - size, - shape, - consistency, - position, - mobility ,- extension

BIMANUAL DIGITAL EXAMINATION2 Assessing the anae:• The vaginal fingers are now

moved into one of the lateral fornices with the abdominal hand moving to the corresponding iliac fossa.

• Assess for any adnexal masses (ovaries and fallopian tubes) on both sides - size, shape, tenderness, etc.

BIMANUAL DIGITAL EXAMINATION3 Assessing the Pouch of

Douglas (recto-uterine pouch):-The vaginal fingers now placed

into the posterior fornix of the vagina and its shape is assessed (normally concave away from the fingers, but may be convex towards the fingers if there is a mass in the Pouch of Douglas).

Combined PR and PV Examination• It is done with one finger inserted per vaginally

and the second finger of same hand per rectally• Aim of the examination is to evaluate the extension

of tumor up to lateral pelvic wall• Both the fingers are moved towards lateral pelvic

wall • If tumor extends to pelvic wall the 2 fingers do not

converge

PAP Smear• Insert the spatula with the endocervical

tip ( the longest part), into the endocervical canal and turn 360 degrees.

• Apply the smear onto the slide – 2 strokes.• The Craigbrush is superior to the spatula if

the transition zone is high and you cannot see it.

• Turn it gently in five complete circles and apply the smear to the slide in gentle strokes.

• Within 20 seconds of taking it, apply the smear onto the glass slide with a light sweeping motions.

• Spray immediately with one spray of fixative, holding the spray bottle upright at about 30cm from the slide, to prevent drying and decay of the smear

• Conventional• Liquid based cytology

Liquid Based Cytology:

•Taken using plasctic spatula•Rinsed in a buffered methanol solution•Sepatrated by centrifugation

Advantages : • avoids false positive,false negative• reduces number of unstaisfactory smears

Pap tests can detect

• The presence of abnormal cells in the cervix

• Infections and inflammations of the cervix

• Symptoms of STDs (With the exception of trichomoniasis, Pap tests cannot identify specific STDs, )

• Thinning of the vaginal lining from lack of estrogen commonly related to menopause

De Vita Oncology , 9th edition

• The U.S. Food and Drug Administration has approved the use of HPV testing in combination with Pap screening as a primary screen

• for cervical disease in women age 30 and above in addition to reflex testing within the ASCUS patient population.

• The FDA concluded that HPV testing was more sensitive than cytology but was concerned about the specificity of primary testing, especially in young women, in whom the prevalence is high and which would lead to excessive follow-up studies.

• An overview of studies on HPV testing in primary cervical cancer screening showed an average sensitivity for detection of CIN 2 or higher of 96%, which was unaffected by patient age.

• Specificity (less than CIN 2) varied between 76% and 96% and was significantly on the lower end in young women.

• Adjusting for women 35 years and above, specificity was 93%.

De Vita Oncology ,9 th Edition , Cancer Screening

Categories for Pap test results:• Normal results:

• If no abnormal cells are seen, then the test result is normal.• If only benign changes are seen, usually resulting from inflammation or

irritation, then the test result is normal.

• Abnormal results:• Atypical cells of undetermined significance (ASCUS, AGUS).• Low-grade squamous intraepithelial lesions (LSIL) or cervical intraepithelial

neoplasia (CIN) 1. These are mild, subtle cell changes, and most go away without treatment.

• High-grade squamous intraepithelial lesions (HSIL) or CIN 2 or 3. Moderate and severe cell changes which require further testing or treatment.

• Carcinoma.

Management options if the Pap test result is abnormal:

• For women with low-grade squamous abnormalities (ASCUS or LSIL), give periodic Pap tests until the abnormality resolves, or a colposcopy referral for persistent lesions.

• Women with glandular abnormalities (AGUS) usually are referred for colposcopy.

• Women with HSIL usually are referred for colposcopy.• Women with HSIL should be treated to remove or destroy

the abnormal cells.

Pap test performance:• Sensitivity = 51% for CIN I or higher

• Range of 37% to 84%

• Specificity = 98% for CIN I or higher • Range of 86% to 100%

• meta-analyses of cross-sectional studies (AHCPR 1999).

• Historical success in developed countries.• High specificity, meaning women with no cervical

abnormalities are correctly identified by the test with normal test results.

• A well characterized screening approach.• May have the potential to be cost-effective in middle-

income countries.

Strengths of cytology:

Limitations of cytology:

• Moderate to low sensitivity:• High rate of false-negative test results• Women must be screened frequently

• Requires complex infrastructure• Results are not immediately available• Requires multiple visits• Likely to be less accurate among post-menopausal women

ACCP. Pap smears: An important but imperfect method. Cervical Cancer Prevention Fact Sheet. (October 2002).

Comparison of Cytology Classification Systems for Cervical Neoplasms

Bethesda system• The Bethesda System used for reporting uniform cervical

cytology results was initially developed in 1988.

• It was updated in 1991 and 2001 to incorporate laboratory and clinical experience.

• The Bethesda System includes a descriptive diagnosis and an evaluation of specimen adequacy.

• Overall, cervical cytology screening programs for the detection of CIN 3 or cancer have reported a range of sensitivities (50% to 75%) and specificities (69% to 94%).

Leibel & Phillips

ENDOCERVICAL CURETTAGE: scraping of mucus membrane by endocervical brush or curettage.

Punch Biopsy• Multiple punch biopsy of the grossly visible lesion should

be adequate to diagnose invasive carcinoma• It is advised that the specimen be taken from all the four

quadrant• Important thing is to obtain specimen from periphery of

lesion with some normal tissue• Biopsy specimen from central area of necrosis or

ulceration may not be sufficient for diagnosis• Dilatation and curettage

Colposcopy

COLPOSCOPY

• Binocular stereoscope giving 10-20 times magnificationTo study cervix when pap smear detect abnormal cellsTo locate the abnormal areas and take biopsyConservative surgery under colposcopic guidenceFollow up

• Visual inspection of acetowhite areas;

• Applying 5% acetic acid

• Acid coagulates protein of nucleus and

cytoplasm and makes the protein opaque

and white

• Dull white plaque with faint border: LSIL

• Thick plaque with sharp border: HSIL

• Visual inspection of acetowhite areas;

• Applying 5% acetic acid

• Acid coagulates protein of nucleus and

cytoplasm and makes the protein opaque

and white

• Dull white plaque with faint border: LSIL

• Thick plaque with sharp border: HSIL

Abnormal areas• Punctation:

Dilated capillaries terminating on the surface appear from the ends as a collection of dots

• Atypical vascular pattern: looped vessels,branching vessels,reticular vessels

Cone Biopsy

• Diagnostic and therapeutic

• Large abnormalities,inner wall

receded into cervical canal,SCJ

not visible

• Cold knife technique under GA

• Large loop excision of

transformation zone

• Laser excision

• Conization must be performed in the following situations:

• no gross lesion of the cervix is noted and an endocervical tumor is suspected;

• the entire lesion cannot be seen with the colposcope; • diagnosis of microinvasive carcinoma is made on biopsy; • discrepancies are found between the cytologic and the

histologic appearances of the lesion; or • the patient is not reliable for all necessary follow-up.

• With careful selection of patients who have a negative positron emission tomography (PET) scan and an MRI with a central lesion <2 cm in width, knife conization with lymphadenectomy may be considered for fertility preservation.

CT• CT provides diagnostic information about the

• presence of metastases, • enlarged lymph nodes, and • the primary tumor.

• On a CT scan, • cervical tumor seen as

• an enlarged, irregular, hypoechoic mass with ill-defined margins.

• Parametrial regions • appear dense when involved, and uterosacral involvement may be seen.

• Lymph nodes appear • enlarged, with most >1 cm on axial dimension considered pathologic.

• The overall accuracy of CT scanning in staging cervical cancer ranges from 63% to 88%.50,52

• In the detection of lymph node abnormalities, the overall accuracy of conventional CT scanning is 77% to 85%,

• Sensitivity - 44% • Specificity - 93%.53

MRI• MRI is frequently used for the

• initial assessment of • the cervical tumor and • of extracervical tumor extension

T1W: isointense

T2W: hyperintense

CE-T1W: hyperintense

• Advantages• Superior imaging resolution• Better soft tissue contrast

• MRI was superior to both TRUS and EUA (examination under anesthesia) in assessing the full extent of bulky tumors and lymph node enlargement.

• MRI was significantly better than clinical examination or CT for detecting uterine-body involvement or measuring tumor size, but no method was accurate at evaluating the cervical stroma.

• MRI was significantly better at detecting the tumor and parametrial involvement.

• MRI also increased detection of involved lymph nodes.• The tumor is less likely to be as visible on MRI for

adenocarcinoma cases, compared to squamous cell cancer.

Perez &Brady,6th edition

CT vs MRI$ Sensitivity Specificity Accuracy *

CT MRI CT MRI CT MRI

Parametrial invasion

55%[44-66 %]

74%[68-79 %]

- - 76% 94%

Lymph nodes 43%[37-57 %]

60%[52-68 %]

- - 86% 86%

Bladder invasion - - 73%[52-87 %]

91%[83-95 %]

- -

Bladder and rectal invasion

71% 75% - - - -

Stromal invasion - - - - 78% 88%

Staging - - - - 65% 90%

$ Bipat S,et al, Gynecol Oncol. 2003 Oct;91(1):59-66*Obs&Gyn,1995;86(1):43-5

Positron Emission Tomography• PET scanning is increasingly used in the evaluation of patients with

invasive cervical cancer, using 2-[18F]-fluoro-2-deoxy-D-glucose (FDG).

• Rose et al. • observed uptake in 91% of the primary tumors in 32 patients with locally

advanced carcinoma of the cervix.

• Compared with surgical staging, PET scanning has a • sensitivity of 75% & • specificity of 92% in detecting para-aortic metastasis.

• PET-CT – • highly accurate localization of focal radiotracer uptake• significantly improved diagnostic accuracy when compared with PET or CT

alone. • The most significant prognostic factor for progression-free survival was the

presence of positive para-aortic lymph nodes on PET imaging.

Grisby et al, JCO 2001

1.PET has a higher sensitivity than CT and higher specificity than MR in detecting bone metastases.

2.The most significant prognostic factor for progression-free survival was the presence of positive para-aortic lymph nodes on PET imaging.

• Maximum standardized uptake value (SUV max) is an independent predictor of death from cervical cancer and is associated with persistent disease.

• The SUV of the pelvic node predicts pelvic disease recurrence. • Squamous cell carcinoma is more often FDG avid than is

adenocarcinoma.

Perez & Brady,6 th edition

FIGO STAGING• International Federation of Gynecology and Obstetrics

has put forth a staging system that depends mainly on clinical examination

• It includes– Inspection Palpation Colposcopy Endo cervical curettage Hysteroscopy Cystoscopy Proctoscopy Intravenous urography X ray to rule out lung and bone mets

STAGING

• Clinical rather than surgical staging• This allows staging to occur in low resource settings• Correlation of FIGO to TNM is poor• Minor changes to 2009 FIGO staging

• Deletion of Stage 0• Subdivision of Stage IIA

• IIA1: tumor ≤ 4 cm with involv. < 2/3 upper vag• IIA2: tumor > 4 cm with involv. <2/3 upper vag

• Not included in the FIGO Staging are-• Lymphangiography• FNAC or Biopsy of LN• MRI,CT,PET• Laparoscopy & Laparotomy

FIGO Staging

Comparing TNM and FIGO• T X – Primary tumor cant be assessed• T 0 – No evidence of primary tumor• T is – Carcinoma in situ(preinvasive ca)• T 1- T3b are similar• T 4 /IV A – Tumor invades mucosa of bladder or rectum and/or extends

beyond,true pelvis

• NX-Regional LN cant be assessed• N0-No regional LN Mets• N I/IIIB-Regional LN mets

• M0-No distant mets• M 1/IV B – Distant mets(including peritoneal spread,involvement of

supraclavicular,mediastinal,paraaortic ln,lung,liver,bone)1.AJCC 2010 2.Leibel & Phillips

AJCC 2010 CANCER STAGING OF UTERINE CERVIX

FIGO no longer includes Stage 0.

• All macroscopically visible lesion even with superficial lesion are staged as IB.

• Patients with hydronephrosis or nonfunction of the kidney ascribed to extension of the tumor are classified as stage IIIB regardless of the pelvic findings.

• Other prognostic factors,such as endometrial extension of cervical carcinoma,stromal invasion,lymphatic/vascular permeation and involvement of lateral parametrium(as opposed to medial parametrium) in Stage II B ,are not included in the system.

• Suspected invasion of the bladder or rectum should be confirmed by biopsy.

• Bullous edema of the bladder and swelling of the mucosa of the rectum are not accepted as definitive criteria for staging.

• A few caveats about clinical staging should be remembered:

• A biopsy, not a cervical cytologic smear, is necessary to establish the diagnosis.

• The physical examination should include a survey of the skin, careful palpation of lymph node-bearing areas, speculum examination, and a bimanual rectovaginal examination.

• Only the procedures and studies allowed by FIGO can be used in clinical staging.

• Once the stage is determined, it cannot be changed. For instance, a woman who has clinical stage IB and has a metastatic para-aortic node detected at the time of radical hysterectomy still has stage IB disease.

• Patients seen after treatment initiation should be listed as having unstaged cervical carcinoma.

• If cancer remains after therapy has been completed or if invasive cancer is documented within 6 months of treatment conclusion, the patient still has the original stage disease, but it is classified as “persistent” in most institutions.

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