cin&cancer cervix undergraduate
DESCRIPTION
undergraduate course lectures in Obstetrics &Gynecology Prepared by Dr Manal Behery Professor of OB>NE Faculty of medicine ,Zagazig UniversityTRANSCRIPT
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CIN &CANCER CERVIX
DR Manal Behery 2014
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Introduction
– Exocervix – stratified squamous epithelium
● Basal, parabasal, intermediate and superficial layers
– Endocervix – cylindrical epithelium,
– arranged in branching folds– Squamocolumnar junction
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Squamocolumnar junction
– Embryogenesis – upward migration of squamous epi from vaginal plate replacing mullerian epi.
– Location of SCJ – varies with age & hormonal status
● Everts outwards during adolescence, pregnancy & OCP use● Regresses into endocervix with menopause, low estrogen
states
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Transformation zone
– Adjacent to SCJ – Most active zone of – squamous metaplasia –– prone to carcinogenic effects
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Most active zone of squamous metaplasia
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Dysplasia
*Lack of normal maturation of cell as they move from basal layer to superficial layer
*Large nuclei more variable in size &shape
*more actively dividing nuclei.
Dysplasia are now referred to as cervical intraepithelial neoplasia ( CIN)
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Precursor lesions for cervical cancer
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History of the Conventional Pap Smear
• Developed by Dr. George N. Papanicolaou in 1940’s
• Most common cancer screening test
• Key part of annual gynecologic examination
Ferris et al. Modern Colposcopy. 2004: 2-4, 49.Photo accessed from http://www.cytology-iac.org/Cytopaths/1998/cytoFall98.htm
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Screening with the Conventional Pap Smear
• Widely available
• Inexpensive
• But not perfect– Screening test – not diagnostic– 7-10% of women need further evaluation– Low sensitivity – need regular repeats
Cervical Cytology Screening. ACOG Practice Bulletin No. 45. 2003; 102:417-27.
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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
Linder J. et al. Arch Pathol Lab Med. 1998; 122: 139-144.
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Cervical Cancer Screening Guidelines
• First screen 3 years after first intercourse or by age 21
• Screen annually with regular Paps or every 2 years with liquid-based tests
• After three normal tests, can go to every three years
• Stop at 65-70 years with history of negative tests
Cervical Cytology Screening. ACOG Practice Bulletin No. 45. 2003; 102:417-27.
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Squamo-Columnar Junction
• Junction of pink cervical skin and red endocervical canal
• Inherently unstable • Key portion of the cervix to
sample• Most likely site of dysplasia
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Ayers Spatula
• Concave end to fit the cervix
• Convex end for vaginal wall and vaginal pool scrapings
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•Use concave end •Rotate 360 degrees•Don’t use too much force (bleeding, pain)•Don’t use too little force (inadequate sample)
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Cytobrush
• Insert ~ 2 cm (until brush is fully inside canal)
• Rotate only 180 degrees (otherwise will cause bleeding)
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Percusion before a Pap Smear
– Avoid menstruation
– Abstain from intercourse, douching, use of vaginal tampons, or contraceptive creams for min of 24-48 hrs
– Avoid touching the cervix before Pap smear
– Discharge from cervix may be removed with a swab without touching the cervix
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PAP Smear Classification
● The Class System (I to IV)
● The CIN System – Based on degree of cellular abnormalities
● The Bethesda System
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Bethesda (2001) reporting of Pap Smear:
– Specimen type – conventional, LBC
– Specimen adequacy – satisfactory, unsatisfactory
– General Categorisation:
● Negative for intra-epithelial lesion● Epithelial cell abnormality● Glandular cell abnormality
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COLPOSCOPY
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In office Colposcopy done after an abnormal pap smear result
Vinegar solution is applied to cervix, abnormal tissue will turn white in color ACETOWHITE ARES
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Fig. 6 Punctation seen with carcinoma-insituand microinvasion.
Fig. 8 Loop diathermy apparatus
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Guidelines for colposcopy
– Negative for intraepithelial abnormality – routine cytological screening
– ASC-H, LSIL, HSIL – colposcopy and biopsy
– AGC – colposcopy, endocervical and endometrial evaluation
– AIS – excision biopsy
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Risk factors
– HPV Infection– Cigarette smoking– Parity– Oral Contraceptive use– Early sexual activity, Multiple partners– STDs– Chronic Immunosuppression
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JA Kahn, NEJM, 2009;361:271
The HPV Life Cycle
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Natural history of HPV infection to Cervical cancer
0–1yrs 0–5yrs
Cervical Cervical CancerCancer
Persistent infection
Low GradePrecancers
(CIN 1)
1–20yrs
HPV infection
High Grade
Precancers (CIN 2/3)
Pinto AP, Crum CP. Clin Obstet Gynecol. 2000;43:352–362.
Recovery: HPV clearance…90%
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• The vaccine only worked in women and
girls who were not already infected with
HPV.
• Gardasil (2006) or Cervarix (2009) are
routinely given to 11- and 12-year-old girls,
and allowed for girls as young as 9.
HVP vaccination
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GARDASIL is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.*VLP = Virus-like particle. 1. Villa LL, Costa RL, Petta CA, et al. Lancet Oncol. 2005;6:271–278.
HPV Vaccine technology
Image courtesy of Dr. Ian Frazer
Real Real ViruViru
ssVacciVacci
nene
– Empty Shell formed by recombinant biotechnology to mimic the viral 3D shape.
– Does not contain infectious DNA。
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Dosing schedule
GARDASIL Intramuscular injection (IM)
Recommended schedule
3 doses at month 0,2,6
CERVARIX Vaccine: 3 doses at month 0,1,6
month
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To prevent vaccine type related
Female: Cervical 、 vaginal 、 vulvar Cancers and genital warts
Male:
+
4-in-1 HPV vaccination Regular Pap screening
HPV vaccine is for men and women
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LEEP VS Conization
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Cervical carcinoma
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Understanding Cancer
• Normally, cells grow and divide to form
new cells as the body needs them. When
cells grow old, they die, and new cells take
their place.
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Understanding Cancer
• Sometimes, this orderly process goes wrong.
New cells form when the body does not need
them, and old cells do not die when they
should. These extra cells can form a mass of
tissue called a growth or tumor.
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Background• Worldwide, cervical cancer is the 2nd leading
cause of cancer death in women
• Squamous cell carcinoma (85%)
• Adenocarcinoma (15%)
• Risk factors for squamous cell cancer– Early coitarche– Greater than 6-8 partners– Cigarette smoking– Oral contraceptives
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• Cervical cancer is most strongly associated with sexually transmitted HPV infection
• During the sexual lifespan of a woman, approximately 70% will have been exposed to HPV
• HPV subtypes are classified into high and low risk groups
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Clinical Picture
● Asymptomatic● Vaginal Bleeding
– Post coital– Intermenstrual spotting– Irregular or Postmenopausal bleeding
● Discharge P/V● Pain referred to flanks● Dysuria, hematuria, rectal bleeding● Massive Haemorrhage, uraemia
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Diagnosis
1- History.• Many women are a symptomatic .• Presented with abnormal routine cx smear• Complain of abnormal vaginal bleeding• I M bleeding• post coital bleeding• perimenopausal bleeding• postmenopausal bleeding• blood stain vaginal discharge
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2- Examination:
• PV exam using cuscu’s speculem
• nothing is found in early stage .
• Mass ,ulcerating fungating in the cervix
• P/V P/R is very helpful.
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Investigations
● Physical Examination– Lymph node examination– Per Vaginum – Bimanual rectovaginal examination
● Radiology Colposcopy – IVP CX biopsy– Barium Enema– X Ray Chest– Skeletal X Ray
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Cervical Biopsy
– Punch biopsy
– LEEP● Outpatient procedure● Diagnosis and therapy at same time● Main side effect – secondary haemorrhage
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Conization
– Cold knife– Laser– If cut margins free from cancer, then almost 100%
disease free follow-up
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CT and MRI
– Evaluation of lymphnodes, liver, urinary tract and bony structures
– Can detect only changes in size of nodes, < 1cm considered as positive
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Patterns of spread
• Direct invasion cervical stroma, vagina, and parametrium.
• Lymphatic spread pelvic and then par aortic lymph nodes
• Hematogenous spread such as lungs, liver, and bone
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Lymphatic Spread
– Primary Group● Parametrial nodes● Paracervical/ureteral nodes● Obturator nodes● Hypogastric nodes● External iliac nodes● Sacral nodes
– Secondary Group● Common Iliac nodes● Inguinal nodes (deep and superficial)● Periaortic nodes
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Cervical carcinoma staging
• Staging is clinical
• FIGO staging
• Based on EUA, cystoscopy +/- sigmoidoscopy
• Does NOT include MRI
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FIGO Staging (2009)
● Stage I – carcinoma confined to cervix– IA: invasive carcinoma diagnosed microscopically.
Stromal invasion depth upto 5 mm and width less than 7 mm
● IA1 – stromal invasion <3mm depth and <7mm width● IA2 – stromal invasion 3-5 mm and <7mm width
– IB: clinically visible lesion confined to the cervix● IB1 – lesion <4 cm or less● IB2 – lesion >4 cm
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Stage II – carcinoma invading beyond uterus but not to pelvic wall or lower 1/3 of vagina
– IIA – Tumour without parametrial invasion● IIA1 – lesion < 4 cm● IIA2 – lesion > 4 cm
– IIB – Tumour with parametrial invasion
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Stage III – tumour extending to lateral pelvic wall/lower third of vagina
● causing hydronephrosis or non-functioning kidney– IIIA – Tumour involves lower 1/3 of vagina, no
extension to pelvic wall– IIIB – Tumour extends to pelvic wall or causing
hydronephrosis/non-functioning kidney
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Stage IV
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Widespread introduction of the Pap begins
Conventional Pap smear LBC
1949 1996 2000’s
HPV testing Vaccine
Cervical cancer prevention: Where have we been and where are we going?
Markers
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The choice of treatment will depend on
• Fitness of the patients
• Age of the patients
• Stage of disease.
• Type of lesion
• Experience and the resources available.
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Therapy
Cervical conization
Simple hysterectomy
Radical hysterectomy
Radiation therapy with chemosensitization
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Stage 1 disease
• Treatment = LLETZ
• Conization
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Stage 1 disease
• Confined to cervix• Treatment • = surgical for 1B1
• Chemo Radiotherapy for 1B2
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Surgical procedure
• The classic surgical procedure is the wertheim’s hystrectomy for stage Ib,IIa, and some cases of IIb in young and fat patient
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Werthemeim’s hystrectomy• Total abdominal hystrectomy including the
parametrium.• Pelvic lymphadenectomy• 3 cm vaginal cuff• The original operation conserved the
ovaries ,since squamouss cell carcinoma does not spread dirctly to the ovaries.
• Oophorectomy should be performed in cases of adenocarcinoma as there is 5-10% of ovarian metastosis
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5 year Survival
• Stage I 70%
• Stage II 51%
• Stage III 33%
• Stage IV 17%
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COMPLICATIONS OF SURGERY
• Haemorrhage: primary or secondary.
• Injury to the bladder, uerters.
• Bladder dysfunction.
• Fistula.
• Lymphocele.
• Shortening of the vagina.
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Lymphedema
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Radiation therapy
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Radiation Therapy
External BeamWhole pelvis or para-aortic window
4000-6000 cGyOver 4-5 weeks
BrachytherapyIntracavitary or interstitial
2000-3000 cGyOver 2 implants
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Pros and Cons
Surgery
Bladder dysfunctionVesico/uretero fistulaBowel obstruction
Ovarian preservationVaginal preservation
Radiation
SigmoiditisRectovaginal fistulaBowel obstructionVesico/uretero fistula
Ovarian failure
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Staging and treatment
• Surgical in women up to stage 1b1
• Chemotherapy
• (cisplatin) ± radiotherapy
• with disease > stage 1b1
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