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CARCINOMA CERVIX
INTRODUCTION AND EVALUATION
Student: Surg Lt Cdr Ankur Shah
Moderator: Lt Col Tony Jose
●
References:
– Berek's and Novak's Gynaecology, 15th
ed
– William's Gynaecology, 2nd
ed
– DiSaia, Creasman Clinical Gynaecologic Oncology,
7th
ed
– Berek and Hacker's Gynaecologic Oncology, 5th
ed
– WHO Weekly Epidemiological Record, No 15 dated
10 April 2009
Introduction
●
Latin - “neck”, entry to womb
●
Anatomy
– 2-4 cm in length
– Cervical canal – antomical external os to internal os
– Histologic internal os – transition from endocervical
to endometrial glands
●
Histology
– Exocervix – stratified squamous epithelium
●
Basal, parabasal, intermediate and superficial layers
– Endocervix – cylindrical epithelium, arranged in
branching folds
●
Squamocolumnar junction
– Embryogenesis – upward migration of squamous
epi from vaginal plate replacing mullerian epi.
– Low vaginal pH stimulates squamous metaplasia
– Location of SCJ varies with age & hormonal status
●
Everts outwards during adolescence, pregnancy & OCP
use
●
Regresses into endocervix with menopause, low
estrogen states
●
Transformation zone
– Adjacent to SCJ
– Most active zone of squamous metaplasia – prone
to carcinogenic effects
●
Risk factor for Cervical cancer
– Metaplasia, most active during adolescence and
pregnancy
Pre-invasive Lesions
●
Squamous epi lesions, considered to be
precursors, but lack features of invasive Ca
●
Cervical cytology – major tool to detect CIN
lesions early before onset of invasive Ca
●
Pap Smear
●
Pap smear
– Conventional smear
●
Smear made directly on glass slide at time of sampling
– Liquid based Cytology
●
Cells collected in liquid transport medium, further
processed to produce a monoloayer of cells on slide
●
Advantage of LBC
– Most of the collected material available for sampling
– Abnormal cells, which are few, obscured, clustered
on conventional Pap are easily visible
●
Before a Pap Smear, ensure:
– 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
PAP Smear Classification
●
The Class System (I to IV)
●
The CIN System
– Based on degree of cellular abnormalities
●
The Bethesda System
●
Bethesda (2001) reporting of Pap Smear:
– Specimen type – conventional, LBC
– Specimen adequacy – satisfactory, unsatisfactory
– General Categorisation:
●
Negative for intra-epithelial lesion
●
Epithelial cell abnormality
●
Other findings that may indicate increased risk
– Interpretation of results
Epidemiology & Risk Factors
●
'Preventable' disease
●
Third most frequently diagnosed carcinoma in
women
●
370,000 cases diagnosed annually
– 78% in developing countries
– Lack of screening
●
Risk factors
– HPV Infection
– Cigarette smoking
– Parity
– Oral Contraceptive use
– Early sexual activity, Multiple partners
– STDs
– Chronic Immunosuppression
●
HPV Infection
– The initiating event in cervical dysplasia and
carcinogenesis
– DNA virus
– More than 100 subtypes
●
Low risk – 6, 11 – cause genital warts, rarely asso with
cancer
●
High risk – 16, 18, 45, 31 – asso with 95% of cervical
cancers
●
HPV 16 predominant subtype – 40-70% of invasive
cervical cancer
– Spread through sexual contact
●
Gains access to the basal layer of the cervical epithelium,
which becomes the viral reservoir
HPV and Ca Cervix
●
Vaccination against HPV
– Recombinant vaccine
●
Prepared from purified structural proteins
– Two types of vaccine
●
Quadravalent – against HPV 6, 11, 16, 18
●
Bivalent – against HPV 16, 18
– Recommended age
●
Before initiation of sexual intercourse
●
Age between 9 – 26 yrs
●
Routine vaccination for girls aged 10-14 yrs
●
Catch-up vaccination for adolescent girls and older
women
●
Dosage schedule
– Quadravalent vaccine – 3 doses 0, 2, 6 months
– Bivalent vaccine – 3 doses 0, 1, 6 months
●
Quadravalent vaccine approved for use in
males for prevention of anogenital warts
●
Duration of protection:
– Quadravalent – 5 yrs
– Bivalent – 6.4 yrs
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
Evaluation
●
Clinical Examination
– Per speculum
– Per rectal examination
– Presence of lymph nodes
– Colposcopy
– Cervical Biopsy
●
Colposcopy
– Examination of cervical, vaginal or vulval epithelia
for identification and evaluation of suspected
malignant or pre-malignant changes
– Biopsy an integral part of the procedure
– Indications
●
In response to abnormal Pap Smear
●
Clinically suspicious cervical lesion
●
Abnormal/unexplained bleeding P/V
●
Persistent vaginal discharge
●
ASCCP Guidelines for colposcopy
– Negative for intraepithelial abnormality – routine
cytological screening
– ASC-H, LSIL, HSIL – colposcopy and biopsy
– ASC-US – Repeat cytology, Reflex testing for HPV.
If still abnormal – colposcopy
– AGC – colposcopy, endocervical and endometrial
evaluation
– AIS – excision biopsy
●
Solutions:
– Normal saline
– Acetic acid, 3 – 5%
– Lugol's iodine (Schiller's solution)
●
Colposcopic Grading – Reid's Colposcopic
Index
– Peripheral margin
– Color
– Vascular patterns
– Lugol's staining
●
Colposcopic Findings of Invasion
– Abnormal blood vessels
– Irregular surface contour
– Color
●
Confirmation by Cervical Biopsy
– Punch biopsy
– LEEP
●
Outpatient procedure
●
Diagnosis and therapy at same time
●
Main side effect – secondary haemorrhage
●
Endocervical location and incomplete excision predictors
for treatment failure (40% recurrence rate)
●
Conization
– Cold knife
– Laser
– Curative procedure, with low recurrence rate (0.6%)
– If cut margins free from cancer, then almost 100%
disease free follow-up
– Post-conization, surgical margins show disease
●
No further treatment necessary, only regular follow up
●
Histologic Subtypes
– Squamous Cell
– Adenocarcinoma
●
Adenoma malignum
●
Villoglandular
– Adenosquamous Carcinoma
●
Glassy cell
●
Adenoid basal cell
●
Adenoid cystic
●
Sarcoma
●
Malignant Melanoma
●
Neuroendocrine carcinoma
●
Tumour Spread:
– Direct Invasion
●
Vaginal mucosa – microinvasive spread
●
Myometrium of lower uterine segment
●
Adjacent structures and parametrium, lateral pelvic wall
●
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
Staging Investigations
●
Physical Examination
– Lymphnode examination
– Per Vaginum
– Bimanual rectovaginal examination
●
Radiology
– IVP
– Barium Enema
– X Ray Chest
– Skeletal X Ray
●
Procedures
– Biopsy, Conization
– Hysteroscopy
– Endocervical Curettage
– Cystoscopy, Proctoscopy
●
Optional Investigations
– CT Scan
– MRI
– USG
– Laparoscopy
– Radionuclide Scanning
Non-invasive diagnostic testing
●
CT Scan-
– Evaluation of lymphnodes, liver, urinary tract and
bony structures
– Can detect only changes in size of nodes, < 1cm
considered as positive
●
MRI-
– Valuable modality to determine tumour size, degree
of stromal invasion, vaginal/corpus extension,
parametrial involvement, lymph node status
– LN evaluation was comparable to CT Scan
●
PET Scan
– Use of radionuclides, which decay with emission of
positrons
– Most commonly used is Fluoro-deoxy-glucose
– Tumour cells actively use glucose, detected on
scanning as area of increased glycolysis
– Delineates extent of disease more accurately, esp
nodes which are not enlarged and distant sites not
picked up by conventional radiology
Pre-Operative Evaluation
●
NICE guidelines for pre-op testing
●
Patients categorised based on
– Age
– Surgical grade (minor, intermediate, major, major+)
– ASA grade
●
Recommended investigations
– Blood counts
– Renal/Liver function tests
– Blood sugar levels
– Xray Chest
–
Staging
●
Clinically staged disease
●
In case of doubt, earlier stage should be
allotted
●
Stage must not be changed because of
subsequent findings on extended clinical
findings or surgical findings
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
●
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
●
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
●
Stage IV
– IVA – Tumour invades mucosa of bladder or rectum
or extends beyond true pelvis
– IVB – Distant metastasis
●
All macroscopically visible lesions, even with
superficial invasion – allot stage Ib
●
Diagnosis of Ia1 and Ia2 should be based on
microscopic examination of tissue, preferably,
cone
●
Vascular space involvement does not alter the
stage of disease
●
Extension of disease to corpus uteri should be
disregarded since it cannot be assessed
clinically
●
Growth fixed to pelvic wall by short and
THANK YOU

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Ca cervix evaluation and staging

  • 1. CARCINOMA CERVIX INTRODUCTION AND EVALUATION Student: Surg Lt Cdr Ankur Shah Moderator: Lt Col Tony Jose
  • 2. ● References: – Berek's and Novak's Gynaecology, 15th ed – William's Gynaecology, 2nd ed – DiSaia, Creasman Clinical Gynaecologic Oncology, 7th ed – Berek and Hacker's Gynaecologic Oncology, 5th ed – WHO Weekly Epidemiological Record, No 15 dated 10 April 2009
  • 3. Introduction ● Latin - “neck”, entry to womb ● Anatomy – 2-4 cm in length – Cervical canal – antomical external os to internal os – Histologic internal os – transition from endocervical to endometrial glands ● Histology – Exocervix – stratified squamous epithelium ● Basal, parabasal, intermediate and superficial layers – Endocervix – cylindrical epithelium, arranged in branching folds
  • 4.
  • 5.
  • 6. ● Squamocolumnar junction – Embryogenesis – upward migration of squamous epi from vaginal plate replacing mullerian epi. – Low vaginal pH stimulates squamous metaplasia – Location of SCJ varies with age & hormonal status ● Everts outwards during adolescence, pregnancy & OCP use ● Regresses into endocervix with menopause, low estrogen states
  • 7.
  • 8. ● Transformation zone – Adjacent to SCJ – Most active zone of squamous metaplasia – prone to carcinogenic effects ● Risk factor for Cervical cancer – Metaplasia, most active during adolescence and pregnancy
  • 9.
  • 10. Pre-invasive Lesions ● Squamous epi lesions, considered to be precursors, but lack features of invasive Ca ● Cervical cytology – major tool to detect CIN lesions early before onset of invasive Ca ● Pap Smear
  • 11. ● Pap smear – Conventional smear ● Smear made directly on glass slide at time of sampling – Liquid based Cytology ● Cells collected in liquid transport medium, further processed to produce a monoloayer of cells on slide ● Advantage of LBC – Most of the collected material available for sampling – Abnormal cells, which are few, obscured, clustered on conventional Pap are easily visible
  • 12.
  • 13. ● Before a Pap Smear, ensure: – 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
  • 14. PAP Smear Classification ● The Class System (I to IV) ● The CIN System – Based on degree of cellular abnormalities ● The Bethesda System
  • 15. ● Bethesda (2001) reporting of Pap Smear: – Specimen type – conventional, LBC – Specimen adequacy – satisfactory, unsatisfactory – General Categorisation: ● Negative for intra-epithelial lesion ● Epithelial cell abnormality ● Other findings that may indicate increased risk – Interpretation of results
  • 16.
  • 17.
  • 18. Epidemiology & Risk Factors ● 'Preventable' disease ● Third most frequently diagnosed carcinoma in women ● 370,000 cases diagnosed annually – 78% in developing countries – Lack of screening
  • 19. ● Risk factors – HPV Infection – Cigarette smoking – Parity – Oral Contraceptive use – Early sexual activity, Multiple partners – STDs – Chronic Immunosuppression
  • 20. ● HPV Infection – The initiating event in cervical dysplasia and carcinogenesis – DNA virus – More than 100 subtypes ● Low risk – 6, 11 – cause genital warts, rarely asso with cancer ● High risk – 16, 18, 45, 31 – asso with 95% of cervical cancers ● HPV 16 predominant subtype – 40-70% of invasive cervical cancer – Spread through sexual contact ● Gains access to the basal layer of the cervical epithelium, which becomes the viral reservoir
  • 21.
  • 22. HPV and Ca Cervix
  • 23. ● Vaccination against HPV – Recombinant vaccine ● Prepared from purified structural proteins – Two types of vaccine ● Quadravalent – against HPV 6, 11, 16, 18 ● Bivalent – against HPV 16, 18 – Recommended age ● Before initiation of sexual intercourse ● Age between 9 – 26 yrs ● Routine vaccination for girls aged 10-14 yrs ● Catch-up vaccination for adolescent girls and older women
  • 24. ● Dosage schedule – Quadravalent vaccine – 3 doses 0, 2, 6 months – Bivalent vaccine – 3 doses 0, 1, 6 months ● Quadravalent vaccine approved for use in males for prevention of anogenital warts ● Duration of protection: – Quadravalent – 5 yrs – Bivalent – 6.4 yrs
  • 25. 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
  • 26. Evaluation ● Clinical Examination – Per speculum – Per rectal examination – Presence of lymph nodes – Colposcopy – Cervical Biopsy
  • 27. ● Colposcopy – Examination of cervical, vaginal or vulval epithelia for identification and evaluation of suspected malignant or pre-malignant changes – Biopsy an integral part of the procedure – Indications ● In response to abnormal Pap Smear ● Clinically suspicious cervical lesion ● Abnormal/unexplained bleeding P/V ● Persistent vaginal discharge
  • 28. ● ASCCP Guidelines for colposcopy – Negative for intraepithelial abnormality – routine cytological screening – ASC-H, LSIL, HSIL – colposcopy and biopsy – ASC-US – Repeat cytology, Reflex testing for HPV. If still abnormal – colposcopy – AGC – colposcopy, endocervical and endometrial evaluation – AIS – excision biopsy
  • 29. ● Solutions: – Normal saline – Acetic acid, 3 – 5% – Lugol's iodine (Schiller's solution) ● Colposcopic Grading – Reid's Colposcopic Index – Peripheral margin – Color – Vascular patterns – Lugol's staining
  • 30.
  • 31. ● Colposcopic Findings of Invasion – Abnormal blood vessels – Irregular surface contour – Color
  • 32. ● Confirmation by Cervical Biopsy – Punch biopsy – LEEP ● Outpatient procedure ● Diagnosis and therapy at same time ● Main side effect – secondary haemorrhage ● Endocervical location and incomplete excision predictors for treatment failure (40% recurrence rate)
  • 33. ● Conization – Cold knife – Laser – Curative procedure, with low recurrence rate (0.6%) – If cut margins free from cancer, then almost 100% disease free follow-up – Post-conization, surgical margins show disease ● No further treatment necessary, only regular follow up
  • 34.
  • 35.
  • 36. ● Histologic Subtypes – Squamous Cell – Adenocarcinoma ● Adenoma malignum ● Villoglandular – Adenosquamous Carcinoma ● Glassy cell ● Adenoid basal cell ● Adenoid cystic ● Sarcoma ● Malignant Melanoma ● Neuroendocrine carcinoma
  • 37. ● Tumour Spread: – Direct Invasion ● Vaginal mucosa – microinvasive spread ● Myometrium of lower uterine segment ● Adjacent structures and parametrium, lateral pelvic wall
  • 38. ● 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
  • 39. Staging Investigations ● Physical Examination – Lymphnode examination – Per Vaginum – Bimanual rectovaginal examination ● Radiology – IVP – Barium Enema – X Ray Chest – Skeletal X Ray
  • 40. ● Procedures – Biopsy, Conization – Hysteroscopy – Endocervical Curettage – Cystoscopy, Proctoscopy ● Optional Investigations – CT Scan – MRI – USG – Laparoscopy – Radionuclide Scanning
  • 41. Non-invasive diagnostic testing ● CT Scan- – Evaluation of lymphnodes, liver, urinary tract and bony structures – Can detect only changes in size of nodes, < 1cm considered as positive ● MRI- – Valuable modality to determine tumour size, degree of stromal invasion, vaginal/corpus extension, parametrial involvement, lymph node status – LN evaluation was comparable to CT Scan
  • 42. ● PET Scan – Use of radionuclides, which decay with emission of positrons – Most commonly used is Fluoro-deoxy-glucose – Tumour cells actively use glucose, detected on scanning as area of increased glycolysis – Delineates extent of disease more accurately, esp nodes which are not enlarged and distant sites not picked up by conventional radiology
  • 43. Pre-Operative Evaluation ● NICE guidelines for pre-op testing ● Patients categorised based on – Age – Surgical grade (minor, intermediate, major, major+) – ASA grade ● Recommended investigations – Blood counts – Renal/Liver function tests – Blood sugar levels – Xray Chest –
  • 44. Staging ● Clinically staged disease ● In case of doubt, earlier stage should be allotted ● Stage must not be changed because of subsequent findings on extended clinical findings or surgical findings
  • 45. 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
  • 46.
  • 47. ● 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
  • 48.
  • 49. ● 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
  • 50.
  • 51. ● Stage IV – IVA – Tumour invades mucosa of bladder or rectum or extends beyond true pelvis – IVB – Distant metastasis
  • 52.
  • 53. ● All macroscopically visible lesions, even with superficial invasion – allot stage Ib ● Diagnosis of Ia1 and Ia2 should be based on microscopic examination of tissue, preferably, cone ● Vascular space involvement does not alter the stage of disease ● Extension of disease to corpus uteri should be disregarded since it cannot be assessed clinically ● Growth fixed to pelvic wall by short and