Week 6 - G - Cervical and Endometrial Cancers Treatment - Surgery, Radiotherapy, Chemotherapy

Question 1

What subtypes of the HPV are main causes of cervical cancer? What percentage of cervical cancer cases does this cause? What is the vaccine against this?

Answer 1

HPV types 16 and 18 - they cause 70% of cervical cancer cases Gardasil - the HPV vaccine protects against types HPV 6&11 (genital warts) and 16&18

Question 2

What is the most common type of cervical carcinoma? What is the other type of cervical carcinoma that is less common? (what HPV subtype is this associated with)

Answer 2

Squamous cell carcinoma - most common type - accounts for 75-95% of cases Adenocarcinoma is the next most common accounting for 5-25% of cervical cancers Adenocarcinomas have a stronger association with HPV 18

Question 3

What are the risk factors for cervical cancer?

Answer 3

Early first period High parity High number of sexual partners (greater than 4) Smoking HPV infectio Long term use of COC - greater than 5 years

Question 4

E6 and E7 are two of the proteins produced by the HPV virus that leads to cancer formation How do these proteins do this?

Answer 4

E6 proteins prevent p53 from making damaged DNA commit suicide

E7 proteins bind to Rb (retinoblastoma protein (protein name abbreviated pRb; gene name abbreviated RB or RB1)) - Retinobalastoma protein prevents excessive cell division

Question 5

What are both p53 and retinoblastoma protein known as?

Answer 5

These are both tumour suppressor genes E6 and E7 are oncogenic proteins - as in they turn off the tumour suppressor genes to promote unregulated cell proliferation

Question 6

What is the difference between proto-ocnogenes and tumour suppressor genes?

Answer 6

Proto-oncogenes - normally direct protein synthesis and cell growth - when mutated cause uncontrolled division Only need one allele to be mutated to stop working Tumour suppresor genes - restrict cell division Need both alleles to be mutated to stop working E6 and E7 simply inactivate the genes so no mutation occurs but the p53 and retinoblastoma protein, tumour suppressor genes are inactive

Question 7

How does cervical cancer present?

Answer 7

Post coital bleeding / itermesntrual bleeding Acute renal failure - urinary problems Foul smelling discharge

Question 8

Describe the staging of cervical cancer

Answer 8

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Question 9

What is the 5year survival rate of Stage IA cervical cancer? What is the 5year survival rate of stage IV cervical cancer?

Answer 9

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Question 10

In women with cervical intraepithelial neoplasia (CIN) treat with: * Colposcopy. * Biopsy and histological analysis. * If moderate to severe abnormalities are found: excision or ablation. What procedures would normally be used for excision?

Answer 10

Would use a Cone biopsy to remove the CIN3 (also known as cervical carcinoma in situ) or a LLETZ biopsy - large loop excision of the transformation zone

Question 11

In women diagnosed with cervical cancer at FIGO, when may disease be managed conservatively? WHat is the conservative manageemnt?

Answer 11

If disease is Stage IA1 (microinvasive disease) it may be managed conservatively - ie it is less than 3mm in depth and less than 7mm in width The conservative management would be cone excision in families wishing to preserve fertility, total hysterecotmy in completed families

Question 12

Microinvasive cervical cancer is defined is as Stage IA1 Early stage disease is Stage IA2 to IIA What is locally advanced disease stage range?

Answer 12

This is Stage IIB to IVA (Locally advanced disease) Stage IVB is metastases

Question 13

What is the treatment for cancer stages IA2 to IIA?

Answer 13

For tumours 4cm (Stage IB2 and Stage IIA2) - then chemoradiation is preferred

Question 14

What is the treatment of choice for any patient with Stage IIB (parametrial involvement) to Stage IVA (local spread to bladder and bowel mucosa)?

Answer 14

This would be chemoradiation as first line

Question 15

For chemoradiation, what is the chemotherapy drug of choice? Radiotherapy * High energy x-rays * Targeted to include tumour +/- nodes What are the two different ways in which radiotherapy is given?

Answer 15

Chemotherapy - give cisplatin (agent of choice in cervical cancer)

Radiotherapy - external beam radiation therapy or internal radiation therapy (brachytherapy)

Anything greater than 4cm or Stage IIBtoIVA onward - chemoradiation

Question 16

What is the 1st line treatment of choice for metastatic disease?

Answer 16

Stage IVB - metastatic disease - combination chemotherapy is the treatment of choice (carboplatin and palcitaxel) In women who are pregnant: Care from the multidisciplinary team and delivery after 35 weeks is the treatment of choice.

Question 17

Endometrial cancer is stage 1 to 4 also Describe each stage

Answer 17

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Question 18

What is the mainstay of treatment for endometrial cancers?

Answer 18

The mainstay of treatment would be to carry out radical hysterectomy with bilateral salpingo-oopherecomy (can give post-op radiotherapy) with adjuvant radiotherapy

Question 19

Radiotherapy can be given as external or brachytherapy (internal) When is either given for endometrial cancers?

Answer 19

Usually vault brachytherapy is given post-op for stages I and II External beam radiotherapy is usually given post-op in Stages III and IV Adjuvant chemo is sometimes given

Question 20

What are risk factors for endometrial cancer?(lifestyle, hormones, genetics)

Answer 20

Obesity Oestrogen - HRT and Tamoxifen (Tamoxifen, sold under the brand name Nolvadex among others, is a medication that is used to prevent breast cancer in women and treat breast cancer in women and men.) Genetics - Lynch Syndrome (HNPCC)

Question 21

Endometrial cancer usually presents with post menopausal bleeding There are two types What are they, their precursors and the mutation associations?

Answer 21

Type 1 -

• * Endometrioid endometrial adenocarcinoma
• * Precursor is atypical hyperplasia
• * Associated with PTEN, K-ras & PIK3CA mutations
• * Accounts for 80%

Type 2 -

• * Serous endometrial adenocarcinoma
• * Precursor is serous intrapepithelial carcioma
• * Associated with p53 (TP53) mutation
• * Accounts for 20%