This document discusses cervical cancer, including its causes, diagnosis, staging, and treatment. It begins with the histology and embryological development of the cervix. Precancerous lesions called cervical intraepithelial neoplasia can develop from persistent HPV infection and potentially progress to cancer over many years if left untreated. Diagnosis involves Pap smear, colposcopy, and biopsy. Staging uses the FIGO system and determines treatment, which may include surgery, radiation therapy, or chemoradiation depending on the stage. The choice of treatment also considers the patient's age and fitness.

1. CIN &CANCER CERVIX
DR Manal Behery
2014

2. Introduction
– Exocervix – stratified squamous
epithelium
● Basal, parabasal, intermediate and
superficial layers
– Endocervix – cylindrical
epithelium,
– arranged in branching folds
– Squamocolumnar junction

3. 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

5. Transformation zone
– Adjacent to SCJ
– Most active zone of
– squamous metaplasia –
– prone to carcinogenic effects

6. Most active zone of squamous metaplasia

7. 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)

8. Precursor lesions for cervical cancer

10. 10
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

11. 11
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.

12. 12
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.

13. 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
13
Cervical Cytology Screening. ACOG Practice Bulletin No. 45. 2003; 102:417-27.

15. 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

16. Ayers Spatula
• Concave end to fit the
cervix
• Convex end for vaginal
wall and vaginal pool
scrapings

17. •Use concave end
•Rotate 360 degrees
•Don’t use too much force (bleeding, pain)
•Don’t use too little force (inadequate sample)

18. Cytobrush
• Insert ~ 2 cm (until brush
is fully inside canal)
• Rotate only 180 degrees
(otherwise will cause
bleeding)

19. 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

20. PAP Smear Classification
● The Class System (I to IV)
● The CIN System
– Based on degree of cellular abnormalities
● The Bethesda System

21. 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

24. COLPOSCOPY

25. 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

27. 27
Fig. 6 Punctation seen with carcinoma-insituand
microinvasion.
Fig. 8 Loop diathermy apparatus

28. 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

29. Risk factors
– HPV Infection
– Cigarette smoking
– Parity
– Oral Contraceptive use
– Early sexual activity, Multiple partners
– STDs
– Chronic Immunosuppression

30. The HPV Life Cycle
JA Kahn, NEJM, 2009;361:271

31. 31
Natural history of HPV infection to Cervical cancer
0–1yrs 0–5yrs
CCeerrvviiccaall
CCaanncceerr
Persistent
infection
Low Grade
Precancers
(CIN 1)
1–20yrs
HPV
infection
High Grade
Precancers
(CIN 2/3)
Recovery: HPV clearance…90%
Pinto AP, Crum CP. Clin Obstet Gynecol. 2000;43:352–362.

32. HVP vaccination
• 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.

33. RReeaall
VVaacccciinnee VViirruuss
33
HPV Vaccine technology
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.
Image courtesy of Dr. Ian Frazer
– Empty Shell formed by recombinant
biotechnology to mimic the viral 3D
shape.
– Does not contain infectious DNA。

34. 34
Dosing schedule
GARDASIL Intramuscular injection (IM)
Recommended schedule
3 doses at month 0,2,6
month
CERVARIX Vaccine: 3 doses at month 0,1,6

35. 35
HPV vaccine is for men and women
To prevent vaccine type related
Female: Cervical 、vaginal、vulvar Cancers and
genital warts
Male:
+
4-in-1 HPV vaccination Regular Pap screening

36. LEEP VS Conization

37. Cervical carcinoma

38. 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.

39. 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.

40. 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

41. • 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

42. 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

43. 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

44. 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.

45. Investigations
● Physical Examination
– Lymph node examination
– Per Vaginum
– Bimanual rectovaginal examination
● Radiology Colposcopy
– IVP CX biopsy
– Barium Enema
– X Ray Chest
– Skeletal X Ray

46. Cervical Biopsy
– Punch biopsy
– LEEP
● Outpatient procedure
● Diagnosis and therapy at same time
● Main side effect – secondary haemorrhage

47. Conization
– Cold knife
– Laser
– If cut margins free from cancer, then almost 100%
disease free follow-up

49. CT and MRI
– Evaluation of lymphnodes,
liver, urinary tract and bony
structures
– Can detect only changes in
size of nodes, < 1cm
considered as positive

50. 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

51. 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

52. Cervical carcinoma staging
• Staging is clinical
• FIGO staging
• Based on EUA, cystoscopy +/- sigmoidoscopy
• Does NOT include MRI

53. 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

55. 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

57. 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

60. Stage IV

61. Cervical cancer prevention:
Widespread
introduction of
the Pap begins
Where have we been and where
Conventional Pap smear LBC
1949 1996 2000’s
HPV testing
Vaccine
are we going?
Markers

62. 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.

63. Therapy
Cervical conization
Simple hysterectomy
Radical hysterectomy
Radiation therapy with
chemosensitization

64. Stage 1 disease
• Treatment =
LLETZ
• Conization

66. Stage 1 disease
• Confined to cervix
• Treatment
• = surgical for 1B1
• Chemo Radiotherapy
for 1B2

67. 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

70. 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

75. 5 year Survival
• Stage I 70%
• Stage II 51%
• Stage III 33%
• Stage IV 17%

76. COMPLICATIONS OF SURGERY
• Haemorrhage: primary or secondary.
• Injury to the bladder, uerters.
• Bladder dysfunction.
• Fistula.
• Lymphocele.
• Shortening of the vagina.

77. Lymphedema

78. Radiation theRapy

80. Radiation Therapy
External Beam
Whole pelvis or para-aortic window
4000-6000 cGy
Over 4-5 weeks
Brachytherapy
Intracavitary or interstitial
2000-3000 cGy
Over 2 implants

81. Pros and Cons
Surgery
Bladder dysfunction
Vesico/uretero fistula
Bowel obstruction
Ovarian preservation
Vaginal preservation
Radiation
Sigmoiditis
Rectovaginal fistula
Bowel obstruction
Vesico/uretero fistula
Ovarian failure

82. Staging and treatment
• Surgical in women up to stage 1b1
• Chemotherapy
• (cisplatin) ± radiotherapy
• with disease > stage 1b1