Download Cancer Cervix.3.2015

Cancer Cervix
By
Maged Abd El Fattah Amine
Assistant Lecturer Of Medical Oncology
South Egypt Cancer Institute
3.2015
*Outline:
- Introduction and Epidemiology.
- Aetiology and Risk factors.
- Pathology.
- Diagnosis.
- Treatment.
- Screening and Prevention.
- Conclusions.
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Introduction
and
Epidemiology
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- Cervical cancer is the third most common cancer in
women, with an estimated 529 828 new cases and 275
128 deaths reported worldwide in 2008.
- Mean age for cervical cancer is 50 years and it peaks
at 35-40 years and 60-64 years.
- More than 85% of the global burden occurs in
developing countries, where it accounts for 13% of all
female cancers.
- the age standardized mortality rate is 10/10 000, more
than three times higher than in developed countries.
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Aetiology
and
Risk factors
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Risk Factors:
- Sexuel intercourse at an early age.
- Multiple sexuel partners.
- Young age at first pregnancy.
- Cigarette smoking.
- HSV infection.
- HPV infection.
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HPV in Cancer Cervix
- It is common knowledge that the most important cause
of cervical cancer is persistent papillomavirus infection.
- The human papillomavirus (HPV) is detected in 99%
of cervical tumors, in particular the oncogenic subtypes
such as HPV 16 and 18.
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*Types of HPV:
- Low risk types: 6 and 11
 Sqcc
-High risk Types:
-Mostly types16, 18, 31, and 33; Other types: (35, 39,
45, 51, 52, 56, 58)
 both Sqcc and Adeno.
- Type 18 is associated with:
- Poorly differentiated histology.
- Higher incidence of lymph node metastases.
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HPV as an
etiology
Sexual Exposure
HPV Infection
Cervical Transformation Zone
Squamous Ep
Columnar Ep
High Risk Types (16,18,31,33)
Low Risk-6,11
Smoking, Hormone, Oral contr. parity,
Altered immune response etc.
Squamous Ca
Adeno Ca
Pathology
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- The WHO recognizes three categories of epithelial
tumors of the cervix:
a- Squamous cell carcinomas account for ∼70%–80%.
b- Adenocarcinomas for ∼10%–15% .
c- Other epithelial tumors including neuroendocrine
tumors and undifferentiated carcinoma.
- Grossly, Carcinomas can be exophytic, growing out of
the surface, or endophytic with stromal infiltration with
minimal surface growth.
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Staging
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* Tumor risk assessment includes:
- tumor size, stage, depth of tumor invasion, lymph
node status, lymphovascular space involvement (LVSI),
and histological subtype.
- Lymph node status and number of lymph nodes
involved are the most important prognostic factors. In
stages IB-IIA, the 5-year survival rate without lymph
node metastasis and with lymph node metastasis is
88%–95% and 51%–78%, respectively.
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Diagnosis
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Presentation:
• Vaginal bleeding.
• Discharge.
• Back pain.
• Superficial ulceration.
• Exophytic tumor.
• May spread to the vaginal fornices,
parametria, bladder or rectum.
• S & S of distant spread.
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Diagnostic work-up:
• History and Physical examination.
• Chest X-ray, CBC, LFTs, RFTs, Urinalysis.
• Cystoscopy, Rectosigmoidoscopy ( if Stage > 3).
• Optional: MRI, CT, US, IVP, PET scan.
• Cervical biopsy.
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Treatment
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- Depending on stage, primary treatment consists of
surgery, radiotherapy, or a combination of
radiotherapy and chemotherapy.
- Several factors affect the decision, include:
1- PS.
2- Operability.
3- Fertility status.
4- Tumor stage.
5- Pathological adverse risk factor i.e. LVI, Grade,
margin, histological type.
- Fertlity preservation is not applicable to patients with
neuroendocrinal tumor or minimal deviation
adenocarcinoma (adenoma malignum) because of lack
of data.
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Stage Ia
Stage
Risk factor
Primary ttt
Alternative ttt
For fertility sparing
Extrafascial Hystrectomy
Conization
Modified radical hystrectomy
+
Pelvic LN dissection
+/- PALN
Radical Trachlectomy
+
Pelvic LN dissection
+/- PALN
Modified radical hystrectomy
+
Pelvic LN dissection
+/- PALN
Radical Trachlectomy
+
Pelvic LN dissection
+/- PALN
-ve margin
Ia1
No LVSI
+ve margin
Ia1 with
LVSI
Or
Ia2
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Stage Ib and Stage IIa
Stage
Primary ttt
Alternative ttt
Ib1
And
IIa1
Radical Hystrectomy
+
Pelvic LN dissection
+/- PALN
Pelvic RT
+
Brachytherapy(dose 80-85gy)
+/-CCRT
Ib2
And
IIa2
Definitive pelvic RT
+
Brachytherapy (dose >85gy)
+
CCT Cispltin based
Radical Hystrectomy
+
Pelvic LN dissection
+/- PALN
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Management of stage I tumor
Adjuvant therapy
i. Observation only:

Negative surgical margin.

Negative pelvic node.

Not bulky tumor.

No parametrium involvement.
ii. Chemoradiation ± vaginal brachytherapy:

Margin: Positive Surgical margin or close vaginal margins (<0.5 cm).

Nodal status: Positive pelvic node.

Bulky primary tumor.

Parametrium involvement.
Management of stage I tumor
Adjuvant therapy
iii. Chemoradiation + Para-aortic LN RTH ± vaginal
brachytherapy:

Positive Para-aortic LN + negative other metastatic workup
iv. Radiotherapy without concurrent chemotherapy:
 Indicated in stage Ia2, Ib1, Ib2 with negative nodes but with
these risk factors
 Lymphovascular invasion
 Deep stromal invasion (> 1/3 of the stroma)
 Bulky primary tumor (> 4cm in size)
 N.B.: The use of concurrent chemotherapy in these conditions is
controversy.
Stage IIb and Stage III and Stage IVa
Accurate Radiological staging (By CT, MRI and /or
PET scan) then:
1.
Negative PALN and Negative other metastatic workup
• Chemoradiation + brachytherapy.
2.
Positive PALN & Negative other metastatic workup
• Chemoradiation + Para-aortic LN RTH ±
brachytherapy.
3.
Positive other metastatic workup
• Systemic treatment
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Stage IVb/Recurrence
-Patients with metastatic or recurrent cervical cancer
are commonly symptomatic. The role of chemotherapy
in such patients is palliative.
- Doublets have better Response rate than Cisplatin
alone.
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Stage IVb/Recurrence
-A recent phase III trial assessed four cisplatin-doublet
regimens (cisplatin–paclitaxel, cisplatin–topotecan,
cisplatin–gemcitabine, and cisplatin– vinorelbine) . No
significant differences in overall survival were seen;
however, the trends for response rate, PFS, and OS
suggest that cisplatin–paclitaxel is the preferred
regimen.
- Although Cisplatin-gemcitabine was not superior to
Cisplatin and paclitaxel, but it was tolerable
(JCOG0505).
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Target therapy

Bevacizumab
 It is considered as second line single agent therapy
for advanced cervical cancer (But still controversy
till now)

Erlotinib
 The combination of E+ CRT is feasible and
showed encouraging data (CR rate of 92.6%)
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Screening
and
Prevention
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- Cervical cancer is a preventable disease due to:
a) long Long pre- cancer state and;
b) effective screening program
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A) Primary prevention:
1. Avoid HPV exposure.
2. HPV vaccination:
1. Bivalent (HPV 16/18) Cervarix®
Contains the L1 protein from two types of HPV (16, 18).
I.M. injection 3 shots 0, 1 and 6 month.
2. Quadrivalent (HPV 6/11/16/18) Gardasil®
Contains the L1 protein from four types of HPV (16, 18, 6, and
11).
I.M. injection 3 shots 0, 2 and 6 month.
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Recommendations of vaccination
The American College of Obstetricians and Gynecologists
(ACOG), in conjunction with the Advisory Committee on
Immunization Practices (ACIP):
1-Routine vaccination of female at 12 years of age.
2- Ideally vaccine should be administered before onset of sexual
activity .
3- Vaccination is recommended for females13-26 years of age who
have not been previously vaccinated.
4- Females 26 years of age or younger who are
lactating/breastfeeding or are immuno-compromised may be
vaccinated.
5- NOT recommended for pregnant women.
6- The HPV vaccine does not eliminate the need for cervical
cytology screening.
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Secondary prevention
(Screening and Early detection
Parameters
Recommendation
Age to start
screening
•
at 21 years old, regardless of sexual history
Screening interval •
age 21–29
•
Screen with cytology alone every 3 years.
* HPV testing should not be used in this age group.
Screening interval •
age 30-65
•
Screen with both cytology and HPV testing every 5
years (preferred) or cytology alone every 3 years.
Screening by HPV testing alone is generally not
recommended.
Secondary prevention
(Screening and Early detection
Parameters
Recommendation
Age to stop
screening
• Age 65
• If the woman has adequate negative
prior screening and is not otherwise at
high risk for cervical cancer
HPVvaccinated
women
Screen according to the same
recommendations as for unvaccinated
women
Pap test
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Conclusions
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- Cervical cancer still represents a major public health
problem even in developed countries.
- HPV plays an essential role in pathogenesis of cervical
cancer.
- Cervical cancer is a preventable disease due to
effective screening and early detection.
- Effective ttt could achieve cure in 80 % of early stage
(I-II) and 60 % of stage (III).
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Any Questions
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THANK YOU
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