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By:-
AHMED GAMAL YASSIN
M.B.B.Ch
1
CERVICAL CANCER
Definition
• Cervical cancer is a preventable HPV-related
malignancy of the uterine cervical mucosa.
• Cervical mucosa: mean tumor arise from epithelium, i.e: type of
tumor is carcinoma (SCC or adenocarcinoma but SCC is the much
more common type).
• The tumor precisely arise from what’s called TZ.
• HPV – related: b/c of HPV is the most important aetiological factor.
• b/c the natural course of the disease is well known, so it deserve to
have screening test, so the disease is preventable condition.
2
Epidemiology
• Cervical cancer is the fourth most common
malignancy in women worldwide.
• More common in developing countries b/c of
early sexual activity due to early marriage, low
socioeconomic state & poor nutrition.
• Incidence mainly in women aged between 20 &
49 years with peak incidence in women aged 40-
49 years & the declines gradually thereafter.
3
Epidemiology (Cont.)
• Incidence higher in black people & mortality is
twice higher than white people.
• Incidence less in muslems & jewishs.
• In developed countries, the incidence start to
decline in the last decades b/c of screening
program.
4
Aetiology
• The cancer occur following CIN which is widely
regarded as a necessary precursor lesion for
carcinoma of cervix.
• CIN is a histological diagnosis and needs
persistent cervical infection with HPV to develop.
• There are about 15 high risk oncogenic subtypes
of HPV, the most common being 16, 18, 31, and
33 & much more common are 16 & 18.
5
Risk factors
• Strong:-
• HPV infection (most common factor ever)
• Age group: women aged between 20 & 49 years with peak
incidence in women aged 40-49 & the declines gradually
thereafter.
• HIV infection.
• Early onset of sexual activity (younger than 18).
• Multiple sexual partners.
• Cigarette smoking (as promoter/ precipitating factor).
• Immunosuppression.
6
Risk factors (Cont.)
• Weak:-
• All other STDs.
• Oral contraceptive use (adenocarcinoma).
• High parity.
• uncircumcised male partner.
• micronutrient malnutrition.
• low serum folate.
• low vitamin C and E levels.
• alcohol abuse.
• low socioeconomic status.
7
Pathophysiology
• The main site of the cancer is TZ.
• TZ: zone at which transformation from squamous
epithelium to columnar one occur at SCJ.
• This continuous metaplasia suggest high mitotic activity
in this area making TZ is the most susceptible site for the
cancer in the cervix.
• This continuous metaplasia kept by acidic PH of vagina,
so as the age of female progress, then metaplasia tend to
creep upward gradually.
8
Pathophysiology (Cont.)
• Therefore, in young female TZ lies in
ectocervix while in older female
(postmenopause) lies in endocervix.
• In presence of presistent HPV infection in
addition to co-factor as smoking, metaplasia
will change to dysplasia & then driving CIN.
9
Normal cervix with transformation zone.
10
Pathophysiology (Cont.)
11
Classification
Histopathological subtypes:-
• Squamous (80%).
• Adenocarcinomas (15%).
• Adenosquamous (3% to 5%).
• Rare: transitional cell, neuroendocrine, small cell,
adenoid cystic, mesonephric, adenoma
malignum, lymphoma, sarcoma.
12
Prevention
• Safe sexual health and effective barrier
contraception.
• Vaccines against HPV-16/18:-
• Vaccination can be done in female aged between 9 to 45 yrs but
recommended age for vaccination is 11 to 12 yrs for all adolescents.
• Regular screening by cervical smear.
13
Screening
• The NHS Cervical Screening Programme (NHSCSP)
presented since the 1980s.
• Regular cervical screening reduces the risk of death from
cervical carcinoma by 75% (but does not eliminate it).
• cervical cancer Screening is cytological study based on
the natural course of cervical cancer as it detect
possibility of CIN (dysplasia) & depend on cervical smear
(aka; pap smear).
14
Types of abnormalities seen in smear:-
• Dyskaryosis
• Increased nuclear/cytoplasmic ratio
• Koilocytosis
• Poikylocytosis
• Mitosis
• Inflammation
All these
changes
suggest
presence of
dysplasia
15
Cervical smear – normal cytology. Cervical smear – severe dyskaryosis.
16
Results of cervical smear
• Normal
• Abnormal:-
• Inflammation: HPV infected cells + inflammatory cells.
• Dysplasia
o LSIL: HPV infected cells + mild dysplasia
suggesting possibility of CIN-1 on biopsy.
o HSIL: HPV infected cells + moderate dysplasia
suggesting possibility of CIN-2 or CIN-3 on biopsy.
o Cancer: HPV infected cells + severe grades of
dysplasia suggesting invasion on biopsy.
• CIN-1: 1/3
thickness
• CIN-2: 2/3
thickness
• CIN-3: full
thickness
17
Results of cervical smear & their Mx
18
• The USPSTF and the ASCCP guideline now recommend
screening in women from age 21 to 65 years as following:-
o For general population (low risk group): every 3 years.
o For high risk group (HPV infection, early sexual activity, smoker……etc): annually.
o After subtotal hysterectomy, after Tx of benign lesion or CIN: annually.
• In 2012, USPSTF guideline introduce HPV test which indicated as a
part of screening program with pap smear provided that screening
performed each 5 years instead of 3 years or can be indicated in
women with borderline nuclear changes in smear or unsatisfactory
smear results in highly suspicious women clinically.
19
Spread
• Direct/ local spread (infiltration) :-
o Upwards or down: to body of uterus or vagina.
o Lateral (dangerous): to parametria (including LN) & may affect ureter.
o Ant. or post: to bladder or rectum (ulcer, hge, fistula, edema).
• Distant spread/ metastasis by lymphatic: once para-
arotic LN involved, then this signify poor prognosis &
case is incurable.
• Distant spread/ metastasis by blood (rare & late): BLBL.
20
Diagnosis
History & examination:-
• Key diagnostic factors:
o presence of risk factors (common).
o abnormal vaginal bleeding (common).
o postcoital bleeding/ contact bleeding (common).
o pelvic pain, dyspareunia (uncommon).
o cervical mass (uncommon).
o cervical bleeding (uncommon).
21
Diagnosis (Cont.)
• Other diagnostic factors:
o mucoid or purulent vaginal discharge (common).
o bladder, renal, or bowel obstruction (uncommon).
o bone pain (uncommon).
o Other manifestations of local or distant spread
(uncommon).
o Other manifestations of complications (uncommon).
22
Diagnosis (Cont.)
Investigations:-
• 1st test to order:
ResultsTest
mass or bleeding.vaginal or speculum examination
• Raised edge, irregular contour.
• Abnormal blood vessels (mosaic or punctate).
• Aceto-white areas with acetic acid.
• Yellow-areas with Schiller iodine.
colposcopy
Confirms diagnosis histologically and identifies
subtype.
biopsy
Indicated when pap smear positive but unsatisfactory.HPV testing23
Cervix with acetic acid. Cervix with CIN and new vessels.
24
• Other tests to consider:
o Indicated for staging & diagnosis of complications:
Diagnosis (Cont.)
ResultsTest
AnaemiaFBC
ElevatedRFT
Elevated (ALP)LFT
MassCXR
AbnormalIVP
AbnormalBarium enema
MassProctoscopy
25
Diagnosis (Cont.)
ResultsTest
MassCystoscopy
AbnormalMRI pelvis
Increased metabolic activity in areas of
involvement
PET whole body
Detection of nodal involvement and
metastases
PET/CT whole body
MassCT of chest/abdomen/pelvis with IV/oral
contrast
26
Diagnosis (Cont.)
• Differential diagnosis:-
o HPV infection
o Pelvic infection
o Nabothian cyst
o Glandular hyperplasia
o Mesonephric remnants
o Endometriosis
o Cervical polyp
o Cervical fibroid
27
FIGO system for staging of cervical cancer
• Stage 0: CIN, preinvasive lesion/ no invasion of
BM.
• Stage 1: confined to cervix:
o Stage 1a: microscopic disease/ invasive carcinoma
but not diagnosed unless by biopsy.
o Stage 1b: macroscopic disease/ visible invasive
carcinoma.
28
FIGO system for staging of cervical
cancer (Cont.)
• Stage 2: extend/infiltrate beyond cervix but
not to pelvic side wall (parametria) or extend
to upper 2/3 of vagina:
o Stage 2a: infiltrate upper 2/3 of vagina.
o Stage 2b: infiltrate parametria.
29
FIGO system for staging of cervical
cancer (Cont.)
• Stage 3: extend/ infiltrate pelvic side wall or
lower 1 /3 of vagina or associated with non-
functioning kidney or hydronephrosis:
o Stage 3a: infiltrate lower 1 /3 of vagina.
o Stage 3b: infiltrate pelvic side wall or associated
with non-functioning kidney or hydronephrosis.
30
31
FIGO system for staging of cervical
cancer (Cont.)
• Stage 4: extend out of true pelvis or infiltrate
bladder or rectum:
o Stage 4a: locally advanced/ extend to adjacent
organ as bladder or bowel.
o Stage 4b: distant metastasis/ extent out of true
pelvis.
32
UICC staging by TMN system
Less commonly used. T staging corresponds to FIGO
staging.
• TX, NX, MX: primary tumor, nodes, or metastases
not assessed.
• N0, M0: Nodes or metastases not involved.
• N1, M1: Nodes or metastases involved.
• Tis: Carcinoma in situ (correspond to higher
grades of CIN).
33
Treatment
Patients with cervical cancer classified according stage of disease
at time of presentation for therapeutic purposes into:-
• Non-pregnant patients:-
o Microinvasive disease: stage Ia1.
o Early stage disease: stage Ia2 to IIa.
o Locally advanced disease: stage IIb to IVa.
o Metastatic disease: stage IVb.
• Pregnant patients: same stages & all of them are treated by
same lines of treatment.
In non-
pregnant
patient, each
stage has its
own line of
treatment.
34
Treatment (Cont.)
(By LEEP)
(By Cisplatin + Radiation)
(By Cisplatin + Radiation)
(By Cisplatin + Radiation)
35
Treatment (Cont.)
(By Cisplatin + Radiation)
(By Cisplatin +
Radiation)
(By Cisplatin + Radiation)
(By bevacizumab + Cisplatin)
(By Cisplatin)
36
Complications
• Bleeding.
• Bladder instability after radical hysterectomy
• Radiation complications: vaginal stenosis, atrophy,
fibrosis, bladder instability, lymphoedema & bowel or
bladder fistulae.
• Leg oedema after lymphadenectomy.
• Excision & ablation techniques complications: preterm
birth.
• Long term sexual dysfunction.37
Prognosis
• Most recurrence happens within 2 years.
• The 5-year survival depends on the stage of the
tumor:
o Stage IA1 - 100%.
o Stage IB2-IIB - 50% to 70%.
o Stage III - 30% to 50%.
o Stage IV - 5% to 15%.
38
Abbreviations:
• USPSTF: United States Preventive Services Task Force
• ASCCP: American Society for Colposcopy and Cervical Pathology
• FIGO: International Federation of Gynecology and Obstetrics
• UICC: International Union Against Cancer
Sources:
• Oxford Handbook of Obstetrics and Gynaecology 3rd Ed. (2013)
• BMJ: Cervical Cancer: Nov 10, 2017
• Gynaecology by Ten Teachers, 19th Ed. (2011)
• Ain-Shams University Gynaecology curriculum (2013)
• Kasr-Alainy University Gynaecology curriculum (2014)
39
THANK
YOU
40

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Cervical cancer

  • 2. Definition • Cervical cancer is a preventable HPV-related malignancy of the uterine cervical mucosa. • Cervical mucosa: mean tumor arise from epithelium, i.e: type of tumor is carcinoma (SCC or adenocarcinoma but SCC is the much more common type). • The tumor precisely arise from what’s called TZ. • HPV – related: b/c of HPV is the most important aetiological factor. • b/c the natural course of the disease is well known, so it deserve to have screening test, so the disease is preventable condition. 2
  • 3. Epidemiology • Cervical cancer is the fourth most common malignancy in women worldwide. • More common in developing countries b/c of early sexual activity due to early marriage, low socioeconomic state & poor nutrition. • Incidence mainly in women aged between 20 & 49 years with peak incidence in women aged 40- 49 years & the declines gradually thereafter. 3
  • 4. Epidemiology (Cont.) • Incidence higher in black people & mortality is twice higher than white people. • Incidence less in muslems & jewishs. • In developed countries, the incidence start to decline in the last decades b/c of screening program. 4
  • 5. Aetiology • The cancer occur following CIN which is widely regarded as a necessary precursor lesion for carcinoma of cervix. • CIN is a histological diagnosis and needs persistent cervical infection with HPV to develop. • There are about 15 high risk oncogenic subtypes of HPV, the most common being 16, 18, 31, and 33 & much more common are 16 & 18. 5
  • 6. Risk factors • Strong:- • HPV infection (most common factor ever) • Age group: women aged between 20 & 49 years with peak incidence in women aged 40-49 & the declines gradually thereafter. • HIV infection. • Early onset of sexual activity (younger than 18). • Multiple sexual partners. • Cigarette smoking (as promoter/ precipitating factor). • Immunosuppression. 6
  • 7. Risk factors (Cont.) • Weak:- • All other STDs. • Oral contraceptive use (adenocarcinoma). • High parity. • uncircumcised male partner. • micronutrient malnutrition. • low serum folate. • low vitamin C and E levels. • alcohol abuse. • low socioeconomic status. 7
  • 8. Pathophysiology • The main site of the cancer is TZ. • TZ: zone at which transformation from squamous epithelium to columnar one occur at SCJ. • This continuous metaplasia suggest high mitotic activity in this area making TZ is the most susceptible site for the cancer in the cervix. • This continuous metaplasia kept by acidic PH of vagina, so as the age of female progress, then metaplasia tend to creep upward gradually. 8
  • 9. Pathophysiology (Cont.) • Therefore, in young female TZ lies in ectocervix while in older female (postmenopause) lies in endocervix. • In presence of presistent HPV infection in addition to co-factor as smoking, metaplasia will change to dysplasia & then driving CIN. 9
  • 10. Normal cervix with transformation zone. 10
  • 12. Classification Histopathological subtypes:- • Squamous (80%). • Adenocarcinomas (15%). • Adenosquamous (3% to 5%). • Rare: transitional cell, neuroendocrine, small cell, adenoid cystic, mesonephric, adenoma malignum, lymphoma, sarcoma. 12
  • 13. Prevention • Safe sexual health and effective barrier contraception. • Vaccines against HPV-16/18:- • Vaccination can be done in female aged between 9 to 45 yrs but recommended age for vaccination is 11 to 12 yrs for all adolescents. • Regular screening by cervical smear. 13
  • 14. Screening • The NHS Cervical Screening Programme (NHSCSP) presented since the 1980s. • Regular cervical screening reduces the risk of death from cervical carcinoma by 75% (but does not eliminate it). • cervical cancer Screening is cytological study based on the natural course of cervical cancer as it detect possibility of CIN (dysplasia) & depend on cervical smear (aka; pap smear). 14
  • 15. Types of abnormalities seen in smear:- • Dyskaryosis • Increased nuclear/cytoplasmic ratio • Koilocytosis • Poikylocytosis • Mitosis • Inflammation All these changes suggest presence of dysplasia 15
  • 16. Cervical smear – normal cytology. Cervical smear – severe dyskaryosis. 16
  • 17. Results of cervical smear • Normal • Abnormal:- • Inflammation: HPV infected cells + inflammatory cells. • Dysplasia o LSIL: HPV infected cells + mild dysplasia suggesting possibility of CIN-1 on biopsy. o HSIL: HPV infected cells + moderate dysplasia suggesting possibility of CIN-2 or CIN-3 on biopsy. o Cancer: HPV infected cells + severe grades of dysplasia suggesting invasion on biopsy. • CIN-1: 1/3 thickness • CIN-2: 2/3 thickness • CIN-3: full thickness 17
  • 18. Results of cervical smear & their Mx 18
  • 19. • The USPSTF and the ASCCP guideline now recommend screening in women from age 21 to 65 years as following:- o For general population (low risk group): every 3 years. o For high risk group (HPV infection, early sexual activity, smoker……etc): annually. o After subtotal hysterectomy, after Tx of benign lesion or CIN: annually. • In 2012, USPSTF guideline introduce HPV test which indicated as a part of screening program with pap smear provided that screening performed each 5 years instead of 3 years or can be indicated in women with borderline nuclear changes in smear or unsatisfactory smear results in highly suspicious women clinically. 19
  • 20. Spread • Direct/ local spread (infiltration) :- o Upwards or down: to body of uterus or vagina. o Lateral (dangerous): to parametria (including LN) & may affect ureter. o Ant. or post: to bladder or rectum (ulcer, hge, fistula, edema). • Distant spread/ metastasis by lymphatic: once para- arotic LN involved, then this signify poor prognosis & case is incurable. • Distant spread/ metastasis by blood (rare & late): BLBL. 20
  • 21. Diagnosis History & examination:- • Key diagnostic factors: o presence of risk factors (common). o abnormal vaginal bleeding (common). o postcoital bleeding/ contact bleeding (common). o pelvic pain, dyspareunia (uncommon). o cervical mass (uncommon). o cervical bleeding (uncommon). 21
  • 22. Diagnosis (Cont.) • Other diagnostic factors: o mucoid or purulent vaginal discharge (common). o bladder, renal, or bowel obstruction (uncommon). o bone pain (uncommon). o Other manifestations of local or distant spread (uncommon). o Other manifestations of complications (uncommon). 22
  • 23. Diagnosis (Cont.) Investigations:- • 1st test to order: ResultsTest mass or bleeding.vaginal or speculum examination • Raised edge, irregular contour. • Abnormal blood vessels (mosaic or punctate). • Aceto-white areas with acetic acid. • Yellow-areas with Schiller iodine. colposcopy Confirms diagnosis histologically and identifies subtype. biopsy Indicated when pap smear positive but unsatisfactory.HPV testing23
  • 24. Cervix with acetic acid. Cervix with CIN and new vessels. 24
  • 25. • Other tests to consider: o Indicated for staging & diagnosis of complications: Diagnosis (Cont.) ResultsTest AnaemiaFBC ElevatedRFT Elevated (ALP)LFT MassCXR AbnormalIVP AbnormalBarium enema MassProctoscopy 25
  • 26. Diagnosis (Cont.) ResultsTest MassCystoscopy AbnormalMRI pelvis Increased metabolic activity in areas of involvement PET whole body Detection of nodal involvement and metastases PET/CT whole body MassCT of chest/abdomen/pelvis with IV/oral contrast 26
  • 27. Diagnosis (Cont.) • Differential diagnosis:- o HPV infection o Pelvic infection o Nabothian cyst o Glandular hyperplasia o Mesonephric remnants o Endometriosis o Cervical polyp o Cervical fibroid 27
  • 28. FIGO system for staging of cervical cancer • Stage 0: CIN, preinvasive lesion/ no invasion of BM. • Stage 1: confined to cervix: o Stage 1a: microscopic disease/ invasive carcinoma but not diagnosed unless by biopsy. o Stage 1b: macroscopic disease/ visible invasive carcinoma. 28
  • 29. FIGO system for staging of cervical cancer (Cont.) • Stage 2: extend/infiltrate beyond cervix but not to pelvic side wall (parametria) or extend to upper 2/3 of vagina: o Stage 2a: infiltrate upper 2/3 of vagina. o Stage 2b: infiltrate parametria. 29
  • 30. FIGO system for staging of cervical cancer (Cont.) • Stage 3: extend/ infiltrate pelvic side wall or lower 1 /3 of vagina or associated with non- functioning kidney or hydronephrosis: o Stage 3a: infiltrate lower 1 /3 of vagina. o Stage 3b: infiltrate pelvic side wall or associated with non-functioning kidney or hydronephrosis. 30
  • 31. 31
  • 32. FIGO system for staging of cervical cancer (Cont.) • Stage 4: extend out of true pelvis or infiltrate bladder or rectum: o Stage 4a: locally advanced/ extend to adjacent organ as bladder or bowel. o Stage 4b: distant metastasis/ extent out of true pelvis. 32
  • 33. UICC staging by TMN system Less commonly used. T staging corresponds to FIGO staging. • TX, NX, MX: primary tumor, nodes, or metastases not assessed. • N0, M0: Nodes or metastases not involved. • N1, M1: Nodes or metastases involved. • Tis: Carcinoma in situ (correspond to higher grades of CIN). 33
  • 34. Treatment Patients with cervical cancer classified according stage of disease at time of presentation for therapeutic purposes into:- • Non-pregnant patients:- o Microinvasive disease: stage Ia1. o Early stage disease: stage Ia2 to IIa. o Locally advanced disease: stage IIb to IVa. o Metastatic disease: stage IVb. • Pregnant patients: same stages & all of them are treated by same lines of treatment. In non- pregnant patient, each stage has its own line of treatment. 34
  • 35. Treatment (Cont.) (By LEEP) (By Cisplatin + Radiation) (By Cisplatin + Radiation) (By Cisplatin + Radiation) 35
  • 36. Treatment (Cont.) (By Cisplatin + Radiation) (By Cisplatin + Radiation) (By Cisplatin + Radiation) (By bevacizumab + Cisplatin) (By Cisplatin) 36
  • 37. Complications • Bleeding. • Bladder instability after radical hysterectomy • Radiation complications: vaginal stenosis, atrophy, fibrosis, bladder instability, lymphoedema & bowel or bladder fistulae. • Leg oedema after lymphadenectomy. • Excision & ablation techniques complications: preterm birth. • Long term sexual dysfunction.37
  • 38. Prognosis • Most recurrence happens within 2 years. • The 5-year survival depends on the stage of the tumor: o Stage IA1 - 100%. o Stage IB2-IIB - 50% to 70%. o Stage III - 30% to 50%. o Stage IV - 5% to 15%. 38
  • 39. Abbreviations: • USPSTF: United States Preventive Services Task Force • ASCCP: American Society for Colposcopy and Cervical Pathology • FIGO: International Federation of Gynecology and Obstetrics • UICC: International Union Against Cancer Sources: • Oxford Handbook of Obstetrics and Gynaecology 3rd Ed. (2013) • BMJ: Cervical Cancer: Nov 10, 2017 • Gynaecology by Ten Teachers, 19th Ed. (2011) • Ain-Shams University Gynaecology curriculum (2013) • Kasr-Alainy University Gynaecology curriculum (2014) 39