Oncology - Cancer screening and tumour markers

Question 1

What is the aim of cancer screening?

Answer 1

Cancer screening looks at asymptomatic individuals for pre cancerous lesions or early cancer, treatment of which can result in cure.

Question 2

What cancers are part of the national screening programme in the UK?

Answer 2

Breast
Cervical
Bowel

Question 3

What is the aim of the cervical screening programme? How are results interpreted?

Answer 3

The cervical screening programme aims to detect pre malignant changes in the cervical epithelium, termed cervical intraepithelial neoplasia (CIN). Depending on the degree of invasion into the endometrial epithelium it is graded as CN I, CN II or CN III. The higher the grade the more likely it is to develop into a malignancy.

Borderline or mild dyskaryosis —> test original sample for HPV:

• if patient negative go back to routine recall
• if positive the patient is referred for colposcopy

Moderate dyskaryosis —> consistent with CN II. Refer for colposcopy

Severe dyskaryosis —> consistent with CN III. Refer for colposcopy

Question 4

What ages are women screened?

Answer 4

Screening starts in the UK at aged 25 and continues up to the age of 64. This upper age limit reflects the fact that it is unlikely a women will develop aggressive cervical malignancy or CIN during the remainder of her lifespan after this age.

A smear test is offered to all women between the ages of 24-64 years:

• 25-49: 3 yearly screening
• 50-64: 5 yearly screening

Currently there is an 80% uptake, but this figure does not reflect the fact that most women who go for screening are least likely to develop the cancer. It is more prevalent in younger women from lower SES and of high sexual activity which are not reflected in the uptake population.

Question 5

How is cervical cancer screening performed?

Answer 5

There is currently a move away from traditional Papanicolaou (Pap) smears to liquid-based cytology (LBC). Rather than smearing the sample onto a slide the sample is either rinsed into the preservative fluid or the brush head is simply removed into the sample bottle containing the preservative fluid.

Advantages of LBC includes
reduced rate of inadequate smears
increased sensitivity and specificity

It is said that the best time to take a cervical smear is around mid-cycle. Whilst there is limited evidence to support this it is still the current advice given out by the NHS.

Question 6

How is bowel cancer screening performed?

Answer 6

Screening is offered to men and women between the ages of 60-74 and takes place every 2 years. Patients over 74 can request screening. Uptake for the screening varies between 25-50% depending upon the area.

Patients are sent a faecal occult blood test in the post. Patients with abnormal results are offered colonoscopy (which is gold standard).

Question 7

Is bowel cancer screening effective?

Answer 7

Most bowel cancers develop from adenomatous polyps. Screening for colorectal cancer has been shown to reduce mortality by 16%. Annual faecal occult blood testing and flexible sigmoidoscopy every 5 years thus have the potential to reduce mortality significantly.

Cancer research UK suggested a few years ago that a single one off flexible sigmoidoscopy in men and women aged between 55-64 could reduce bowel cancer death rates by 43%.

Question 8

What are the current guidelines for colorectal screening?

Answer 8

Those with a very high incidence of colon and/or rectal cancer (e.g. familial polyposis coli, hereditary non polyposis coli, cancer families or ulcerative pan-colitis) should have yearly faecal occult bloods +/- colonscopy.

Rectal examination should be included as part of routine check ups.

Question 9

What women are eligible for breast cancer screening?

Answer 9

The NHS Breast Screening Programme is being expanded to include women aged 47-73 years from the previous parameter of 50-70 years. Women are offered a mammogram every 3 years. After the age of 70 years women may still have mammograms but are ‘encouraged to make their own appointments’.

Question 10

According to NICE guidelines, a woman who has one first or second degree relative diagnosed with breast cancer does NOT need referral unless what factors are present in the family history?

Answer 10

• age of diagnosis < 40 years
• bilateral breast cancer
• male breast cancer
• ovarian cancer
• Jewish ancestry
• sarcoma in a relative younger than age 45 years
• glioma or childhood adrenal cortical carcinomas
• complicated patterns of multiple cancers at a young age
• paternal history of breast cancer (two or more relatives on the father’s side of the family)

Question 11

Women who are at an increased risk of breast cancer due to their family history may be offered screening from a younger age. What patients should be referred to the breast clinic for further investigation?

Answer 11

• one first-degree female relative diagnosed with breast cancer at younger than age 40 years, or
• one first-degree male relative diagnosed with breast cancer at any age, or
• one first-degree relative with bilateral breast cancer where the first primary was diagnosed at younger than age 50 years, or
• two first-degree relatives, or one first-degree and one second-degree relative, diagnosed with breast cancer at any age, or
• one first-degree or second-degree relative diagnosed with breast cancer at any age and one first-degree or second-degree relative diagnosed with ovarian cancer at any age (one of these should be a first-degree relative), or
• three first-degree or second-degree relatives diagnosed with breast cancer at any age

High risk patients under 40 can be referred for an MRI which is a highly sensitive screening method.

Question 12

Why is breast cancer screening controversial?

Answer 12

The mortality from breast cancer since the introduction of a screening programme has steadily declined. But the incidence of breast cancer has increased. This relates to DCIS which is a precursor lesion of cancer, and accounts for 20% of screen detected cancers (calcified lesion). DCIS is currently treated as cancer, which may involve surgery, radiotherapy and/or chemotherapy. But the natural history of DCIS is uncertain, with evidence to suggest that 50% of DCIS lesions may in fact be benign. So screening over detects DCIS leading to unnecessary treatment.

Also, treatment has improved so much over the last 20 years that screening may no longer be needed.

Question 13

What are the different types of tumour marker?

Answer 13

Tumour markers can be divided into:

• monoclonal antibodies against carbohydrate or glycoprotein antigens
• tumour antigens
• enzymes (e.g. alkaline phosphatase, neurone specific enolase)
• hormones (e.g. calcitonin, ADH)

Tumour markers usually have a low specificity.

Question 14

Give some examples of tumour markers that are monoclonal antibodies

Answer 14

CA 125 = ovarian cancer
CA 19-9 = pancreatic cancer
CA 15-3 = breast cancer

Question 15

Give some examples of tumour markers that are tumour antigens

Answer 15

PSA = prostate carcinoma
Alpha feto protein (AFP) = hepatocellular or teratoma
Carcinoembryonic antigen (CEA) = colorectal cancer
S-100 = melanoma, schwannomas
Bombesin = SCLC, gastric cancer, neuroblastoma