Cancer diagnosis: is it a tumour?

Screening
1. ... In the UK
  1. Only done when... (criterea)
    1. Condition is an important health problem, well understood disease, recognisable at an early stage treatment is more effective at early stages...
      1. Suitable/acceptable tests exist, facilities exist to cope with abnormalitites detected...
        Resources exist to allow for multiple/repeated screens at age of risk and the harms and costs are outweighed by the benefits
  2. Screens
    1. Cervical
      1. Well defined disease progression (Normal, CIN I, CIN II and CIN III)
      2. Women aged 25-6yrs
        25-49yrs (highest risk) = every 3yrs
        50-64yrs (lower risk) = every 5yrs
        >65yrs - not screened unless they havn't been screened since 50yrs or abnormal smear seen
        If 80% of the population screened then there would be a 95%reduction in the death rate from cervical cancer
        "Jade Goody" effect
        33,000 more smears than expected, 35% during the month of her death
        The biggest increase seen in 25-29yrs age range
        Now this surge in women being screened is already trailing off
        A negative screen can provide 41-69% protection in women aged 20-54yrs and 73% protection in >55yrs
        ... with 3-yearly intervals between screens
        Protection drops with 5-yearly intervals
      3. Two techniques...
        (Classical) 'Pap' smear
        Spatula scrapes cells from the surface of the cervix
        Must ensure to swab the 'transition zone' (where most neoplasms occur)
        = the border between the stratified squamous epithelium of the cervix and the columnar mucous epithelium of the vagina
        Swab spread onto glass slide and observed (microscopy)
        (Newer) Liquid-based cytology
        Same swab taken as in the 'pap' smear
        Swab tip is broken off into a solution of preservative
        This is spun to remove debris and other obstructive material (mucous etc.)
        Automated machine removes the cells and spreads a thin layer onto a glass slide
        Slide observed under microscope
      4. HPV and cervical cancer
        Epidemiological studies indicate cervical cancer as an STD
        HPV found in 85% of cervical carcinomas
        High risk forms (= 16, 18, 31, 33, 35, 55 - found in ~100% of invasive cervical carcinomas) and low risk forms (= 6 and 11 - cause genital warts only)
        HPV also involved in; anus, penile, vulval, throat and mouth cancers too
        Pathogenesis and carcinogenesis
        Sexual contact -> HPV exposure
        Cervical transmformation zone (infection)
        Integration of viral DNA into host DNA
        HPV proteins E6 (inhibits p53) and E7 (inhibits; p53, p21 and Rb) - cause avoidance of apoptosis and premature entry into S-phase
        Squamous / endocervical columnar differentiation
        High/low grade squamous intraepithelial lesions / glandular intraepithelial lesions
        Carcinogenic risk factors; smoking, oral contraceptives, high parity (given birth many times), altered immune status, gene mutations, time
        Invasive; squamous carcinoma / adenocarcinoma
        75% of population exposed to HPV (only 50% to high risk HPV)
        of these - 10% have persistent CIN (cervical intraepithelial neoplaisa)
        1.3% progress to invasive carcinoma
        0.4% die
        HPV vaccination
        Started in (sept) 2008; offered to all 12-13 and 17-18yo females
        x3 injections over 6 (or 12) months
        Two vaccines
        Cervarix (protects against HPV 16 and 18)
        Gardasil (protects against HPV 6 AND 11)
        Unanswered questions
        How long does protection last?
        Is there cross-protection (from other serotypes)?
        Will other types of HPV become carcinogenic?
        In US 62.5% of males are HPV positive
        Need to vaccinate boys?
      5. High risk HPV found in ~100% of invasive cervical carcinomas
        Screen for these HPV's by PCR?
    2. Breast
      1. Based on mammography - aimed at detecting calcification
        Calcification associated with ductal carcinoma in situ (DCIS)
        Pre-invasive
        No metastatic capacity
        Curable
      2. NHS breast screening programme (BSP): invites women 50-70yrs (highest risk)
        screened every 3 years
        Is this too long?
        Saves 1400 lives per year in England
        Is 50yrs the right age?
        Now inviting women at 47yrs
        Is this screening necessary?
        BBC health news - reports a third of breast cancer as being 'harmless'
        An independent review, published in the Lancet (2012) - highlights the problem of overdiagnosing cancer
        This is the detection of a cancer that would not otherwise cause that person a problem during their lifetime
        Waste of time/resources?
        Unecessary treatment and follow up to the individual?
        Further screening, biopsies - unecessary pain/stress?
        The future of breast screening
        It is unlikely that breast cancer screening will stop
        Instead aim is to target high risk individuals - family history / high mammographic density
        Clinical trial in discussion: 'watch and wait' method for DCIS
      3. Once imaging done - biopsy
        Fine needle aspirate (sample fluid around mass)
        Core needle (removes a 'core' of mass)
        Vaccum (removes a larger sample of mass)
        Large core biopsy (larger core - may also remove healthy tissue)
        Surigical (entire mass cut out under anaesthetics)
    3. Bowel
      1. 1 in 20 people develop colorectal cancer (3rd most common cancer in UK and 2nd leading cause of death (after lung))
      2. Screening aimed at detecting the non-malignant polyps (adenomas) - usually present early as blood in stool
        Based on faecal occult blood (FOB) testing
        Who?: men and women 50-69yrs
        When?: every 2yrs
        Results: 98% have normal result
        2% have positive FOB
        Invited for colonoscopy
        50% of these - normal
        40% of these - adenoma
        10% of these - carcinoma (mostly early stage)
        Risk: 1/1500 chance in bowel perforation
  3. Currently no screen for...
    1. Ovarian
      1. In 2008... 6,500 cases; 4,400 deaths
        5th most common cancer in women (lifetime risk = 1 in 54)
        Accounts for 6% of deaths from cancer in women (more then any other gynae cancer in women)
      2. No current test specific enough
        Two tests being trialled
        CA125
        Circulating tumour marker
        Raised in 85% of ovarian cancer cases
        Raised in 50% in early stages of ovarian cancer
        Other causes can raise this marker
        Trans-vaginal ultrasound
        Ultrasound probe is inserted into the vagina and imaging of the deeper reproductive organs possible through the vaginal wall
        Being used in a screening trial (UKCTOCS - UK collaborative trial of ovarian cancer screening)
        Screening of general female population 50-74yrs
        Women selected at random from GP lists and invited
        To date 10,000 post-menopausal women screened
        Detected 58 cancers
        Missed 12 cancers (6 of these were early stage)
        Group 1 - annual CA125 measure if abnormal U/S
        Group 2 - annual U/S, if abnormal CA125
        Group 3 - No screening
    2. Prostate
      1. No screening programme - but a risk management programme
        Based on advice to take up Prostate-specific antigen (PSA) testing
        PSA gives a lot of false negatives
        10% of all men 50-65yrs will have raised PSA
        Only 25% of these will have prostate cancer
        Next step: trans-rectal ultrasound (U/S) and biopsyn under prophylactic antibiotics
        Positive result: treatment is by radical prostatectomy or radical radiotherapy
        Prostate cancer is highly hetergenous (differs massively between individual)
        Therefore no evidence that early treatment improves survival
        More men die with - rather than from - prostate cancer
2. Other screening techniques?
  1. Microarrays
    1. Gavaert, 2009
      1. Used microarrays to identify gene clusters associated with tissue specific primary tumours and their metastases
        Recognised; breast, colon, lung, ovarian, prostate, kidney and thyroid/kidney clusters of gene expression in epithelial cancers

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Cancer diagnosis: is it a tumour?

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	Created by maisie_oj about 11 years ago