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.
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
4.
5. Transformation zone
– Adjacent to SCJ
– Most active zone of
– squamous metaplasia –
– prone to carcinogenic effects
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)
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.
14.
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
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
26.
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
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。
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
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
48.
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
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
54.
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
56.
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
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.
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
68.
69.
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
71.
72.
73.
74.
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.
82. Staging and treatment
• Surgical in women up to stage 1b1
• Chemotherapy
• (cisplatin) ± radiotherapy
• with disease > stage 1b1
Editor's Notes
Primary cervical cancer screening essentially began with the introduction of the Pap Smear.
Introduced in the 1940’s, by Dr. George N. Papanicolaou, the pap smear eventually became the standard screening test for cervical cancer and pre-malignant lesions.
The Pap test is based on a relatively simple principle. Cells from squamous epithelium exfoliate over time. Thus, the cells removed for cytologic examination represent epithelial cells, normal or abnormal, found at the surface.
Widespread use of the pap smear has decreased cervical cancer deaths by 70%.
Reference: Ferris et al. Modern Colposcopy. 2004: 2-4, 49.
Cervical cytology screening is, in many respects, the ideal screening test.
Cervical cancer has a defined premalignant phase of many years, which allows repeated tests to significantly reduce the impact of individual false-negative test results.
Cervical cytology is inexpensive and is readily accepted among American women.
However, cervical cytology, is not a diagnostic test. The sensitivity of the pap smear is low (ranges from 47-85%) and the specificity is high (95-98%).
Reference: Cervical Cytology Screening. ACOG Practice Bulletin No. 45. 2003; 102:417-27.
In 1996, the FDA approved the first of two currently available liquid-based thin-layer cytology preparations for cervical screening.
Liquid-based thin-layer cervical cytology was introduced to help reduce the potential sampling errors. The Thin-Prep method appears to have increased sensitivity for detecting cancer precursor lesions over the conventional method, but the degree to which sensitivity is increased is unknown. The reported increase in sensitivity may make this method especially useful in women who are screened infrequently (fewer false negatives).
The difference in specificity between the liquid-based and conventional tests has not been determined. Although an increase in sensitivity will permit earlier detection of cancer precursor lesions, any decrease in specificity can result in increased cost and morbidity from false-positive diagnoses.
Both the conventional test and the liquid-based thin-layer test can be effective in population screening.
Providers selecting a cervical cytology method should consider the screening history of their patient, the cost of the test, and the possible effects of false-negative or false-positive results.
Reference: ACOG Practice Bulletin. Cervical Cytology Screening. 2003; 45:1-11.
The next several slides will review the newest guidelines for cervical cancer screening from the American Cancer Society, the United States Preventive Services Task Force and the American College of Obstetricians and Gynecologists.
These guidelines specifically state how often screening should be done, when to initiate screening and when screening can be discontinued.
Reference: Cervical Cytology Screening. ACOG Practice Bulletin No. 45. 2003; 102:417-27.
In obtaining the Pap smear, it is important to sample the &quot;Squamo-columnar Junction.&quot; This is the circular area right at the opening of the cervix where the pink, smooth skin of the cervix meets the fiery-red, fragile, mucous-producing lining of the cervical canal. If there is going to be a problem with cancer or precancerous changes, it is this area that is most likely to be effected. This area is also known as the SQJ, or transition zone.
The Ayers spatula is specially designed for obtaining Pap smears. The concave end (curving inward) fits against the cervix, while the convex end (curving outward) is used for scraping vaginal lesions or sampling the &quot;vaginal pool,&quot; the collection of vaginal secretions just below the cervix.
The spatula is made of either wood or plastic. Both give very satisfactory results.
Push the cytobrush into the canal, no deeper than the length of the brush (1.5 cm - 2.0 cm). Rotate the brush 180 degrees (half a circle) and pull the cytobrush straight out. Don&apos;t keep spinning the brush round and round or you will cause bleeding. Even the 180 degree rotation may cause a little bleeding but usually it doesn&apos;t.
Despite these strong results, experts say women still need to get regular Pap tests to look for cervical cancer.
The HPV types targeted by the vaccine aren&apos;t the only ones that can cause cancer, so even vaccinated women aren&apos;t 100% protected from this disease. Furthermore, it&apos;s been only about 5 years since studies began; the participants are still being followed to see how long the vaccine&apos;s protection will last.
And, the vaccine only worked in women and girls who were not already infected with HPV 16 or 18. That&apos;s why federal health officials and the American Cancer Society recommend giving Gardasil routinely to 11- and 12-year-old girls, and allow it for girls as young as 9. Vaccinating girls before they become sexually active and have a chance to catch HPV gives them the best chance of being protected by the vaccine.
Cancer begins in cells, the building blocks that make up tissues. Tissues make up the organs of the body.
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.
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.
Tumors can be benign or malignant.
Slide 19:
In recent decades, concerns about the sensitivity of conventional cervical cytology led to the evaluation of alternatives. (Bullet 1) Liquid based cytology (LBC) was first introduced into clinical practice following the 1996 FDA-licensing of a thin layer cytology system. (Bullet 2) An HPV test using hybrid capture technology was FDA-approved for the management of ASC-US Pap results in 1999 and as a co-test with the Pap for women ages 30 and over in 2003. A newer signal amplification HPV DNA test and type-specific test for HPV 16 and18 were licensed by the FDA for clinical use in early 2009. (Bullet 3) An HPV vaccine became available when the FDA licensed a quadrivalent vaccine in June, 2006. This vaccine was approved for use in girls and women 9-26 years of age and included protection against two high risk and two low risk HPV types. A second HPV vaccine became available after the FDA licensed a bi-valent HPV vaccine, for the prevention of two high risk types, in October, 2009, for use in females up to age of 25 (Bullet 4) In the future, other bio-markers for increased risk for cervical cancer, such as mRNA and P16 are expected to be introduced to the market.
