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MohmmadRjab Seder
PALESTINE POLYTECHNIC UNIVERSITY
Faculty of Medicine and Health Sciences
The Cervix - Overview
Squamocolumnar Junction (SCJ)
The area between the original SCJ and the current SCJ is called as
“Transformation Zone” TZ
Cervix Histology
Cervical Cancer - Overview
oAlso called: invasive cervical carcinoma (ICC).
oCervical cancer is the third/fourth most common
cancer among women globally.
oClassified into:
o Premalignant/Precancer disease of the cervix.
o Malignant disease of the cervix.
oMore than 95% of cervical CA is due to HPV.
oCervical CA can be cured if diagnosed at an
early stage and treated promptly.
Epidemiology
oAbout 90% of the new cases and deaths worldwide in
2020 occurred in low- and middle-income countries.
oAccording to PHC/MoH; there are only small number of
diagnosed cervical CA in Palestine. (Health Annual Report
2021)
Worldwide - In 2022
604,000 new cases
342,000 deaths
In USA
Clinical Presentation
oCervical cancer often has no symptoms in its early stages.
oThe most common symptom as it develops is vaginal
bleeding.
oIrregular and/or abnormally heavy menstrual periods.
oPostcoital bleeding (PCB).
oPostmenopausal bleeding (PMB).
oOther symptoms:
oUrinary incontinence.
oLeg pain or swealing.
oBack pain.
oUnexplained weight loss.
Aetiologies and Risk Factors
Human papillomavirus (HPV) infection (95% of cases)
Having a family history of cervical cancer
Multiple sexual partners
Smoking (2x)
HIV (6x)
Immunosuppression
Co-infection with Chlamydia or HSV
Long-term use of OCPs
Having multiple full-term pregnancies (Multiparity)
Young age at first full-term pregnancy
A diet low in fruits and vegetables
Protective
Factors:
o Intrauterine device
(IUD) use.
o Condom use in
woman with
multiple sexual
partners.
NOTE
Human Papilloma Virus
oOncogenic viruses.
oThere are more than 100 different types of HPV classified
as low-risk or high-risk types, depending on their ability to
cause cancer.
oHigh-risk types 16, 18, 31, 33, and 45 → cervical cancer.
oLow-risk types 6 and 11 → benign warts.
oTransmitted by sexual intercourse.
oHPV infection → premalignant → malignant (How??)
Pathophysiology
oHPV have two proteins known as E6 and E7 which turn off
some tumor suppressor genes, such as p53 and Rb.
oMost women with HPV don’t get cervical cancer. But:
HPV + Coexisting Risk Factors → Cervical CA
o Oncogenes: genes that help cells grow, divide, and stay alive.
o Tumor suppressor genes: genes that help keep cell growth
under control or make cells die at the right time.
Premalignant
Disease of the
CERVIX
Pre-cancers of the cervix
oCells in the TZ do not suddenly change into cancer.
oInstead, the normal cells of the cervix first gradually
develop abnormal changes that are called pre-
cancerous.
oSeveral terms are used to describe these pre-cancerous
changes, including:
oCervical intraepithelial neoplasia (CIN)
o Squamous intraepithelial lesion (SIL)
o Dysplasia
What is the difference
between the terms SIL
and CIN???
Premalignant Malignant
Types of Cervical Cancer
oSquamous cell carcinoma
o70-80% of cervical cancers.
oDevelop from cells in the exocervix.
oAdenocarcinoma
o20% of cervical cancers.
oDevelop from glandular cells of the endocervix.
oAdenosquamous/mixed carcinomas
oLess commonly.
oHave features of both squamous cell carcinomas and
adenocarcinomas.
Other rare
types of cancer
also can
develop in the
cervix. Such as
small cell,
melanoma,
sarcoma and
lymphoma.
NOTE
Investigations and Diagnosis
oHPV testing
oCervical cytology
oPap smear
oLiquid-based cytology (LBC)
oCervical biopsy
oColposcopy
oMetastatic workup; pelvic examination, CXR, intravenous
pyelogram, cystoscopy, and sigmoidoscopy.
Pap Smear
oA procedure to test for
cervical cancer in women.
oUsed to screen for cervical
cancer.
oCost effective screening
method.
Pap Smear – Video
Pap Smear
Liquid-based cytology (LBC)
oLBC is better than a Pap test.
oProduce a thin layer of cells on the slide.
LBC
Abnormal cervical cytology shows squamous cells at
different stages of maturity (dyskaryosis)
Colposcopy
oUsed for both diagnosis and treatment.
oMagnification: 5-20 fold.
oThe application of acetic acid and
iodine solutions highlights abnormal
areas of the cervix can be biopsied.
oAcetic acid causes nucleoproteins
within cells to coagulate temporarily;
therefore, areas of increased cell
turnover, including CIN, appear white.
Cervix with acetic acid
Colposcopy - Video
Colposcopy – Video
Cervical Biopsy
oRemove tissue from the cervix to test for abnormal cells or
precancerous conditions.
oGold standard for diagnosis.
Pelvic Examination
Checking vulva, vagina, cervix,
ovaries, uterus, rectum and pelvis
for any abnormalities.
Pelvic exam findings
o Friable cervix
o Erosions
o Cervical mass
o Bleeding
o Fixed adnexa
A progressive cervical adenocarcinoma:
The image shows a rapidly progressing mass protruding from the cervix.
Cystoscopy
Prevention
Treatment of Premalignant Disease of
the Cervix
oAim of treatment: eradicate CIN.
oLow-grade CIN:
o 60% regresses spontaneously.
o Cold coagulation.
o Cone biopsy (Conization).
oHigh-grade CIN:
o Treatment + excision or ablation.
o Diathermy (thermal ablation).
o Cold coagulation.
o Cone biopsy (Conization).
Cold Coagulation.
oProcedure to treat women with abnormal cells on their
cervix, by destroying the abnormal cells with a heated
probe.
Conization
oA procedure in which a
cone-shaped piece of
abnormal tissue is removed
from the cervix.
Diathermy
oAKA: cervical cautery.
Malignant
Disease of the
CERVIX
Cancer is diagnosed when CIN breaks the
basement membrane.
Clinical Presentation
oCervical cancer often has no symptoms in its early stages.
oThe most common symptom as it develops is vaginal
bleeding.
oIrregular and/or abnormally heavy menstrual periods.
oPostcoital bleeding (PCB).
oPostmenopausal bleeding (PMB).
oOther symptoms:
oUrinary incontinence.
oLeg pain or swealing.
oBack pain.
oUnexplained weight loss.
Pathophysiology
oCervical tumours are locally infiltrative in the pelvic area,
but also spread via lymphatics.
oIn the late stages, spread via blood vessels.
oThe tumour can grow through the cervix to reach the
parametria, bladder, vagina and rectum.
oMetastases can occur, therefore, in pelvic (iliac and
obturator) and para-aortic nodes and, in the later stages,
liver and lungs.
Types of Cervical Cancer
oSquamous cell carcinoma
o70-80% of cervical cancers.
oDevelop from cells in the exocervix.
oAdenocarcinoma
o20% of cervical cancers.
oDevelop from glandular cells of the endocervix.
oAdenosquamous/mixed carcinomas
oLess commonly.
oHave features of both squamous cell carcinomas and
adenocarcinomas.
Other rare
types of cancer
also can
develop in the
cervix. Such as
small cell,
melanoma,
sarcoma and
lymphoma.
NOTE
Staging
Clinical Staging may be done through:
oClinical examination
oCervical biopsy (Assess malignancy and tumour type)
oEndoscopy
o Hysteroscopy
o Cystoscopy
o Proctoscopy
oImaging studies
o Intravenous pyelogram (IVP): to evaluate for urinary tract obstruction
o CT
o CXR (exclude lung metastases)
o MRI (Assess local spread)
o PET
Staging
and
prognosis
of cervical
cancer
(By FIGO)
Staging - Video
Management
Depends on the stage.
oPreclinical lesions; stage IA
oClinical invasive cervical carcinoma: stages IB-IV
oSurgery
oRadiotherapy
oPalliative care
Preclinical lesions; stage IA
oLocal excision.
oTotal simple hysterectomy.
oModified radical hysterectomy: surgery to remove the
uterus, cervix, upper part of the vagina, and nearby
ligaments and tissues.
Clinical invasive cervical carcinoma:
stages IB
oRadical hysterectomy.
oBilateral pelvic node dissection (Wertheim’s hysterectomy).
oRadical trachelectomy (surgical removal of the cervix and
upper part of the vagina).
Clinical invasive cervical carcinoma:
stages II-IV
oChemoradiation = Radiotherapy + chemotherapy.
oRadiotherapy:
oExternal beam radiotherapy.
oInternal radiotherapy (brachytherapy).
Brachytherapy
External beam radiotherapy
References
o Kenny, L., & Bickerstaff, H. (Eds.). (2017). Gynaecology by ten teachers, 20th edition (20th ed.). CRC Press.
o Kaplan Medical. (2018). USMLE Step 2 CK Lecture Notes 2019: 5-book set. Kaplan Publishing.
o American Cancer Society. Retrieved September 18, 2022, from https://www.cancer.org/search.html?q=cervix.
o World Health Organization. (2022, February 22). Cervical Cancer. https://www.who.int/news-room/fact-
sheets/detail/cervical-cancer#:~:text=Cervical%20cancer%20is%20the%20fourth,%2Dincome%20countries%20(1).
Thank You

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CERVICAL CANCER

  • 1. MohmmadRjab Seder PALESTINE POLYTECHNIC UNIVERSITY Faculty of Medicine and Health Sciences
  • 2. The Cervix - Overview
  • 3. Squamocolumnar Junction (SCJ) The area between the original SCJ and the current SCJ is called as “Transformation Zone” TZ
  • 5. Cervical Cancer - Overview oAlso called: invasive cervical carcinoma (ICC). oCervical cancer is the third/fourth most common cancer among women globally. oClassified into: o Premalignant/Precancer disease of the cervix. o Malignant disease of the cervix. oMore than 95% of cervical CA is due to HPV. oCervical CA can be cured if diagnosed at an early stage and treated promptly.
  • 6. Epidemiology oAbout 90% of the new cases and deaths worldwide in 2020 occurred in low- and middle-income countries. oAccording to PHC/MoH; there are only small number of diagnosed cervical CA in Palestine. (Health Annual Report 2021)
  • 7. Worldwide - In 2022 604,000 new cases 342,000 deaths
  • 9. Clinical Presentation oCervical cancer often has no symptoms in its early stages. oThe most common symptom as it develops is vaginal bleeding. oIrregular and/or abnormally heavy menstrual periods. oPostcoital bleeding (PCB). oPostmenopausal bleeding (PMB). oOther symptoms: oUrinary incontinence. oLeg pain or swealing. oBack pain. oUnexplained weight loss.
  • 10. Aetiologies and Risk Factors Human papillomavirus (HPV) infection (95% of cases) Having a family history of cervical cancer Multiple sexual partners Smoking (2x) HIV (6x) Immunosuppression Co-infection with Chlamydia or HSV Long-term use of OCPs Having multiple full-term pregnancies (Multiparity) Young age at first full-term pregnancy A diet low in fruits and vegetables Protective Factors: o Intrauterine device (IUD) use. o Condom use in woman with multiple sexual partners. NOTE
  • 11. Human Papilloma Virus oOncogenic viruses. oThere are more than 100 different types of HPV classified as low-risk or high-risk types, depending on their ability to cause cancer. oHigh-risk types 16, 18, 31, 33, and 45 → cervical cancer. oLow-risk types 6 and 11 → benign warts. oTransmitted by sexual intercourse. oHPV infection → premalignant → malignant (How??)
  • 12. Pathophysiology oHPV have two proteins known as E6 and E7 which turn off some tumor suppressor genes, such as p53 and Rb. oMost women with HPV don’t get cervical cancer. But: HPV + Coexisting Risk Factors → Cervical CA o Oncogenes: genes that help cells grow, divide, and stay alive. o Tumor suppressor genes: genes that help keep cell growth under control or make cells die at the right time.
  • 13.
  • 15. Pre-cancers of the cervix oCells in the TZ do not suddenly change into cancer. oInstead, the normal cells of the cervix first gradually develop abnormal changes that are called pre- cancerous. oSeveral terms are used to describe these pre-cancerous changes, including: oCervical intraepithelial neoplasia (CIN) o Squamous intraepithelial lesion (SIL) o Dysplasia What is the difference between the terms SIL and CIN???
  • 17. Types of Cervical Cancer oSquamous cell carcinoma o70-80% of cervical cancers. oDevelop from cells in the exocervix. oAdenocarcinoma o20% of cervical cancers. oDevelop from glandular cells of the endocervix. oAdenosquamous/mixed carcinomas oLess commonly. oHave features of both squamous cell carcinomas and adenocarcinomas. Other rare types of cancer also can develop in the cervix. Such as small cell, melanoma, sarcoma and lymphoma. NOTE
  • 18. Investigations and Diagnosis oHPV testing oCervical cytology oPap smear oLiquid-based cytology (LBC) oCervical biopsy oColposcopy oMetastatic workup; pelvic examination, CXR, intravenous pyelogram, cystoscopy, and sigmoidoscopy.
  • 19. Pap Smear oA procedure to test for cervical cancer in women. oUsed to screen for cervical cancer. oCost effective screening method.
  • 20. Pap Smear – Video
  • 22. Liquid-based cytology (LBC) oLBC is better than a Pap test. oProduce a thin layer of cells on the slide.
  • 23. LBC Abnormal cervical cytology shows squamous cells at different stages of maturity (dyskaryosis)
  • 24. Colposcopy oUsed for both diagnosis and treatment. oMagnification: 5-20 fold. oThe application of acetic acid and iodine solutions highlights abnormal areas of the cervix can be biopsied. oAcetic acid causes nucleoproteins within cells to coagulate temporarily; therefore, areas of increased cell turnover, including CIN, appear white. Cervix with acetic acid
  • 27. Cervical Biopsy oRemove tissue from the cervix to test for abnormal cells or precancerous conditions. oGold standard for diagnosis.
  • 28. Pelvic Examination Checking vulva, vagina, cervix, ovaries, uterus, rectum and pelvis for any abnormalities. Pelvic exam findings o Friable cervix o Erosions o Cervical mass o Bleeding o Fixed adnexa
  • 29. A progressive cervical adenocarcinoma: The image shows a rapidly progressing mass protruding from the cervix.
  • 32. Treatment of Premalignant Disease of the Cervix oAim of treatment: eradicate CIN. oLow-grade CIN: o 60% regresses spontaneously. o Cold coagulation. o Cone biopsy (Conization). oHigh-grade CIN: o Treatment + excision or ablation. o Diathermy (thermal ablation). o Cold coagulation. o Cone biopsy (Conization).
  • 33. Cold Coagulation. oProcedure to treat women with abnormal cells on their cervix, by destroying the abnormal cells with a heated probe.
  • 34. Conization oA procedure in which a cone-shaped piece of abnormal tissue is removed from the cervix.
  • 37. Cancer is diagnosed when CIN breaks the basement membrane.
  • 38. Clinical Presentation oCervical cancer often has no symptoms in its early stages. oThe most common symptom as it develops is vaginal bleeding. oIrregular and/or abnormally heavy menstrual periods. oPostcoital bleeding (PCB). oPostmenopausal bleeding (PMB). oOther symptoms: oUrinary incontinence. oLeg pain or swealing. oBack pain. oUnexplained weight loss.
  • 39. Pathophysiology oCervical tumours are locally infiltrative in the pelvic area, but also spread via lymphatics. oIn the late stages, spread via blood vessels. oThe tumour can grow through the cervix to reach the parametria, bladder, vagina and rectum. oMetastases can occur, therefore, in pelvic (iliac and obturator) and para-aortic nodes and, in the later stages, liver and lungs.
  • 40. Types of Cervical Cancer oSquamous cell carcinoma o70-80% of cervical cancers. oDevelop from cells in the exocervix. oAdenocarcinoma o20% of cervical cancers. oDevelop from glandular cells of the endocervix. oAdenosquamous/mixed carcinomas oLess commonly. oHave features of both squamous cell carcinomas and adenocarcinomas. Other rare types of cancer also can develop in the cervix. Such as small cell, melanoma, sarcoma and lymphoma. NOTE
  • 41. Staging Clinical Staging may be done through: oClinical examination oCervical biopsy (Assess malignancy and tumour type) oEndoscopy o Hysteroscopy o Cystoscopy o Proctoscopy oImaging studies o Intravenous pyelogram (IVP): to evaluate for urinary tract obstruction o CT o CXR (exclude lung metastases) o MRI (Assess local spread) o PET
  • 43.
  • 45. Management Depends on the stage. oPreclinical lesions; stage IA oClinical invasive cervical carcinoma: stages IB-IV oSurgery oRadiotherapy oPalliative care
  • 46. Preclinical lesions; stage IA oLocal excision. oTotal simple hysterectomy. oModified radical hysterectomy: surgery to remove the uterus, cervix, upper part of the vagina, and nearby ligaments and tissues.
  • 47. Clinical invasive cervical carcinoma: stages IB oRadical hysterectomy. oBilateral pelvic node dissection (Wertheim’s hysterectomy). oRadical trachelectomy (surgical removal of the cervix and upper part of the vagina).
  • 48. Clinical invasive cervical carcinoma: stages II-IV oChemoradiation = Radiotherapy + chemotherapy. oRadiotherapy: oExternal beam radiotherapy. oInternal radiotherapy (brachytherapy).
  • 50. References o Kenny, L., & Bickerstaff, H. (Eds.). (2017). Gynaecology by ten teachers, 20th edition (20th ed.). CRC Press. o Kaplan Medical. (2018). USMLE Step 2 CK Lecture Notes 2019: 5-book set. Kaplan Publishing. o American Cancer Society. Retrieved September 18, 2022, from https://www.cancer.org/search.html?q=cervix. o World Health Organization. (2022, February 22). Cervical Cancer. https://www.who.int/news-room/fact- sheets/detail/cervical-cancer#:~:text=Cervical%20cancer%20is%20the%20fourth,%2Dincome%20countries%20(1).