Chapter 2.4 cancer screening

general oncology from devita presentation

1. Screening part 2
Dr Devang Patel

2. Cervical cancer screening
•Screening is performed using
•cervical cytology (Pap/LBC)
•human papillomavirus (HPV) test,
•a combination of the two tests.
The best time is:
•Avoid smear- taking during
menstruation.
•Avoid in the presence of obvious
vaginal infection.
•Avoid within 48 hrs of use of vaginal
creams or pessaries or douching.
•Avoid within 24 hrs of intercourse.
•Avoid lubrication of cervix while
preliminary pelvic examination.
Good communication with the
pathologist is essential.

3. •Cell samples for cervical cytology and human papillomavirus (HPV) testing are obtained during
the speculum examination
•Specimens for cytology —
•the conventional Pap smear and
•the liquid- based, thin layer preparation.
•For both methods, cells are obtained from the external surface of the cervix (ectocervix) and the
cervical canal (endocervix) to evaluate the transformation zone (squamocolumnar junction), the
area at greatest risk for neoplasia

4. •Cervical cytology has evolved over the years.
•The original Pap smear used an ectocervical spatulato apply
a specimen (“smear”) to a glass slide.
•It later included an endocervical brush.
•The slide is then rapidly fixed to avoid air-drying; the usual
fixatives are either ethyl ether plus 95 percent ethyl alcohol
or 95 percent ethyl alcohol alone.
•If spray fixatives are used, the spray should be held at least
10 inches away from the slide to prevent disruption of cells
by the propellant
•The smear was fixed, stained, and manually examined under
a microscope.
•That method is still used today, but a liquid- based/thin- layer
system capable of being analyzedby computer is gaining in
popularity

5. •LIQUID-BASED THIN LAYER CYTOLOGY,
•the collecting device is placed into a liquid fixative solution and vigorously
swirled or rotated ten times in the solution.
•The liquid-based/thin- layer preparation systems
•ThinPrepPap Test
•BD SurePath
•Designed to remove obscuring nonepithelial cells and distribute cells
evenly on a slide.
•Centrifuged to remove excess blood and debris.
•The cells are then transferred to the slide in a single layer.
•An advantage of some liquid- based systems is the ability to use a single
specimen for cytology and testing for HPV.
•With conventional smears, a separate HPV test specimen has
to be obtained

7. LBC vs Pap Test
•↑Sn up to 12% better for the detection of abnormalities of LSIL with LBC compared with the Pap
smear.
•No difference between the Spof LBC and Pap smear.
•The English pilot study showed a statistically significant ↓ in the number of inadequate samples,
•Reduced the pressure on the workforce because of fewer inadequate and clearer to read samples.
•Reduced levels of anxiety in women because fewer need repeat tests and because they receive their
results more quickly.
•Remnant cells may be use for additional test e.gHPV DNA testing.

9. SAMPLE INTERPRETATION(cytology)
traditional categories-mild, moderate, and severe dysplasia and carcinoma in situ.

10. ASCs differ from normal cells but do not meet criteria for LSIL or HSIL.
LSILs are usually due to a transient HPV infection.
HSILs are more likely to be due to a persistent HPV infection and are more likely to progress to cervical cancer
than LSIL lesions
•Glandular cell abnormalities
(features suggestive of adenoca )
•Atypical glandular cells (AGC):
endocervical, endometrial, or not
otherwise specified AGCs,
•favorneoplastic Endocervical or
not otherwise specified
•Endocervical adenocarcinoma in
situ (AIS)
•Adenocarcinoma
•Squamous cell abnormalities:
•Atypical squamous cells (ASC),
which are categorized as either of
undetermined significance (ASC-
US)
•Cannot exclude high- grade
squamous intraepithelial lesions
(ASC-H)
•LSIL-correlates with CIN1
•HSIL-correlates with CIN2, CIN3,
and carcinoma in situ

14. Mx in brief-
•The ASCUS-LSIL Triage Study (ALTS) evaluated women with abnormal
Pap smears. The investigators concluded that women with ASC-US
should be tested for HPV.
•Those who are HPV positive should receive colposcopy.
•In addition, because most women with LSIL or HSIL had HPV infection,
immediate colposcopy and biopsy of lesion are recommended
•Invasive cancers should be dealt as per std guidelines

15. HPV testing
•HPV screening can be used as
•along with cytology (“cotesting”),
•in response to an abnormal cytologic test “reflexive testing”
•as a stand-alonetest.
•One advantage of the LBC over the conventional pap smears is that they make reflexive
testing easier to perform-no need to call patient again
•Among women 30 to 69 yrsof age, the Sn of the Pap + HPV testing was 95% compared
with 55% for the Pap test alone
•HPV testing is especially useful because of its NPV.
•Whereas a +ve HPV test isn’t diagnostic of cervical dz, a -veHPV test strongly suggests
that the abnormal Pap does not represent a premalignant condition.

16. •The utility of the HPV test is limited in younger women coz >1/3 of women in
their 20swho have not received the HPV vaccine have active cervical HPV
infections at any given time.
•majority of these infections and resultant dysplasia will regress and resolve within
an 8-to 24-mth period.
•HPV infection in women older than 30 yrs is more likely to be persistent and
clinically significant.
•For women older than 30 yrs, screening for the presence of HPV DNA or RNA
appears to be superior to cytology in identifying women at risk.
•The risk of cervical cancer also increases with age, and most cervical cancer
deaths occur in women older than 50 yrs.

19. Visual Inspection
Involves 3 different approaches:
•Visual inspection of cervix with
acetic acid (VIA).
•Visual inspection with
magnification (VIAM).
•Visual inspection after
application of Lugol’siodine
(VILI).

20. VIA
•Applying 3% to 5% acetic acid and apply to the cervix liberally.
•When acetic acid is applied to normal squamous epithelium, little coagulation occurs in
the superficial cell layer, as this is sparsely nucleated.
•Areas of CIN and invasive cancer undergo maximal coagulation due to their higher
content of nuclear protein (in view of the large number of undifferentiated cells
contained in the epithelium).
•This prevent light from passing through the epithelium. As a result, the sub- epithelial
vessel pattern is obliterated and the epithelium appears densely white.
•In CIN, acetowhite is restricted to the transformation zone close to the
squamocolumnarjunction, while in cancer it often involves the entire cervix.

22. Test negative Test Postivie
Suspicious for cancer

23. SCREEN &
TREAT
approach

24. VILI
•Lugoliodine is applied over the cervix.
•Squamous epithelium contains glycogen, whereas precancerous lesions and invasive cancer contain little or no
glycogen.
•Iodine is glycophilic and is taken up by the squamous epithelium, staining it mahogany brown or black.
•Columnar epithelium does not change color, as it has no glycogen.
•Immature metaplasia and inflammatory lesions are at most only partially glycogenatedand, when stained, appear as
scattered, ill-defined uptake areas.
•Precancerous lesions and invasive cancer do not take up iodine (as they lack glycogen) and appear as well-defined,
thick, mustard or saffron yellow areas.

26. Test Negative Test Positive Suspicious for cancer

27. VIA vs VIAM vs VILI
•VILI has the highest Sp , detecting 75 per cent of all cases of HSIL compared
with VIA and VIAM which detected <2/3
rd
of cases.
•Sn. VILI 91.8% compared to those of VIA (76.9%) and VIAM (64.2%).
•The yellow colour changes associated with a positive VILI test result could
be recognized with much greater ease by trained health workers compared
with the acetowhitelesions associated with VIA.

28. Cervical Screening Recommendations(2017-ACS)
<21 yrs-no screening (regardless of their age of sexual initiation).
begin screening at 21 yrs.
21 to 29 yrs -cytology screening 3 yrly(pap/LBC) HPV testing should not be
performed in this age group ,although it can be used to follow ASC-US.
30 to 65 yrs -“cotesting”5 yrly.It is also acceptable to continue screening every 3
years with cytology alone.
Discontinue screening after age 65 years if
•3 consecutive -vecytology or
•2 consecutive -veHPV test within the 10-yr period before ceasing screening,
with the most recent test occurring within the past 5 yrs.
h/o total hysterectomy for noncancerous conditions –don’t screen
regardless of age, no annual screening by any screening method.
HPV vaccinated -screen as per mentioned schedule.

29. USPSTF screening in 21 to 65 yrs with cytology (Pap smear) every 3 yrs
For 30 to 65 yrswho want to lengthen the screening interval, screening for HPV
infection every 5 years.
There is no recommendation for cotesting with cytology and HPV.
The USPSTF recommends against screening for cervical cancer with HPV testing,
alone or in combination with cytology, in women younger than age 30 years.
The ACS and USPSTF are agreed that women younger than 21 yrsshould not be
screened and women older than 65 yrscan discontinue screening after 10 years of
normal screening

30. Colon cancer screening
•Colorectal cancer screening involves
•stool testing for blood or DNA associated with polyps or cancer
•structural examinations looking for polyps or early cancers
1)FOBT-
•identifies Hgb by peroxidase reaction turns the guaiac-impregnated paper blue.
•Several guaiac reagents are marketed; Hemoccult-SENSAis more sensitive than Hemoccult,
Hemoccult-II, or Hemoccult-R and is the preferred test for screening.
•rehydrated with distilled water before testing-↑Sn ↓Sp↑ false+ results.
•general consensus- gFOBTsamples should not be rehydrated prior to processing

31. •a restrictive diet during testing may not be necessary. It is not necessary to avoid oral iron
supplements
•vitamin C restrtictionto <250 mg/d × 3 days prior to sampling.
Large doses of vitamin C false-vetests
•Use of low- dose aspirin-usually common in screening age groups
•↑ r/o upper and lower GI bleeding
•↓PPV of gFOBTs
•3 consecutive bowel movements should be sampled
•A single stool specimen obtained during an office rectal examination is not sufficient
•P/R Ex may induce microtraumafalse+ result

32. advantages :
•not require trained clinicians to perform test
•not require bowel prep
•Noninvasive
•Demonstrated effectiveness in RCTs
disadvantages:
•not a good test for the detection of adenomas, which usually do not bleed. The Sn for advanced
adenomas is substantially less than for cancers.
•Diet modification
•3 samples
•large number of false+ results.
2)Fecalimmunochemical tests (FIT)-stool tests that react to human Hb and don’t react to Hb in
dietary products.
•FIT requires only one stool sample
•does not require restrictions to diet or medications
•They appear to have higher Sn and Spfor CRC compared to FOBT tests

33. •more Spfor lower GI sources of bleeding than guaiac testing because FIT detects
only human globin and therefore does not detect upper GI bleeding (since the
globin is digested in transit)
•Aspirin generally does not need to be temporarily discontinued
•Dietary restrictions are not needed
•requires only one sample-higher adherence.
•FIT is more expensive than guaiac-based tests
•The optimal interval for FIT screening is not known, although FIT is usually done
annually

34. 3)FecalDNA testing-look for DNA sequences specific to colorectal polyps & CRC.
•have ↑Sn+Spcompared to FOBT.
•A newer multiplex stool DNA test (MT-sDNA, also known as FIT-DNA), Cologuard,
combines testing stool for DNA mutations and methylation markers using a gene
amplification technique and testing for Hgb with FIT.
•Sn of Cologuard-not affected by cancer stage or location of the colonic lesion.
•Cologuard-approved by US-FDA ,August 2014 as a screening test for colorectal
carcinoma

35. 4)Flexible sigmoidoscopy :
•It is estimated that flexible sigmoidoscopy can find 60% to 80% of cancers and
polyps found by colonoscopy.
•A prospective RCT of once-only flexible s’scopydemonstrated a 23%↓ in CRC
incidence and a 31% ↓ in CRC mortality after f/up of 11.2 yrs.
•
PLCO trial- 21% ↓ in CRC incidence and a 26% ↓ in CRC mortality with 2
s’scopiesdone 3 to 5 years apart compared with the usual care group after f/up
of 11.9 yrs.
•In both studies, there was no effect on proximal (i.e., right and transverse colon) lesions due to the limited reach of the scope.

36. 5)Colonoscopy -preferred screening method in the US, although there have been
no prospective, RCTs of colonoscopy screening
•ANY positive screening test  diagnostic colonoscopy.
•Quality of the colonoscopicexamination is an issue.
•In studies involving repeat colonoscopy by a second physician, 21% of all adenomas were
missed, including 26% of 1- to 5-mm adenomas and 2% of adenomas 10 mm or more in
length.
•Requires bowel preparation
•the risk of bowel perforation

37. 6)CT colonography or virtual colonoscopy - allows a physician to visually
reproduce the endoscopic examination on a computer screen
•less invasive
•higher compliance rate
•require a colonic prep
•finding on CT requires a f/up diagc’scopy.
•The rate of extracolonic findings of uncertain significance is high

39. Current Recommendations(ACS)
avg-risk
adults
begin
screening
at age of
45 yrs. Annual high Sn FOBT or FIT
Multitarget stool DNA testing 3yrly
Flexible sigmoidoscopy every 5 yrs
Colonoscopy every 10 yrs
DCBE every 5 yrs
CT colonography every 5 yrs

40. The USPSTF
•screening adults aged 50-75 yrs
•aged 76-85 yrscan be evaluated individually for screening
1.High sensitivity stool-based methods every year
2.FIT-DNA stool testing every 1 or 3 yrs
3.Colonoscopy every 10 yrs
4.CT colonography every 5 yrs
5.Flexible sigmoidoscopy every 5 yrs
6.Flexible sigmoidoscopy every 10 yrs+ FIT every yr

41. Patients at High Risk for Colorectal Cancer

49. Lung cancer screening
•The Mayo Lung Project (MLP)- 1971 ->9,200 male smokers
•randomized them to sputum cytology /CXR every 4 mthsfor 6 yrsor to have
these same tests performed annually.
•At 13 yrsof f/u, there were more early-stage cancers in the intensively screened
arm than in the control arm, but the number of advanced tumors was nearly
identical.
•Despite an increase in 5-yr survival (35% versus 15%), intensive screening was not
associated with a reduction in lung cancer mortality.

50. •meta-analysis of the 3 studies found that more frequent screening was associated
with ↑rather than ↓, in lung cancer mortality when compared with less frequent
screening.
•A study conducted in Czechoslovakia in the 1980s also failed to show a reduction
in lung cancer mortality with CXR screening.
•NCI conducted the PLCO trial at 10 sites across the US.
•a prospective, randomized trial of nearly 1,55,000 men and women aged 55 to 74 years.
•Participants were randomized to receive annual, single-view, CXR for 4 years versus routine
care.
•With 13 years of follow-up, no significant difference in lung cancer mortality was observed.

51. NCCN abt LDCT
parameter LD CT Conventional CT
mSv 1.5 7-8
time 15 sec Several min
Sharpness of images Better
Sn & Spfor detection of lung lesionsimilar similar

54. NLST trial

64. Lung RADs

65. Prostate cancer screening
•Although PSA is prostate specific, it is not prostate cancer specific and may be elevated in a variety of
conditions (e.g., BPH, prostatitis,trauma) as well as in ca prostate.
•PSA screening introduces substantial lead-time and length bias as well as being associated with a high false-
veand false+ rates and having a low PPV.
•
In the PCPT, cancer was found on end- of-study biopsies at all PSA levels ,
10% 0.6 and 1.0 ng/mL
6% 0 and 0.6 ng/mL,
suggesting a continuum of prostate cancer risk and
no cut point with simultaneously high Sn and high Sp.
•
HG dzwas also documented at all PSA levels, albeit at an overall frequency of only 2.3% of men with PSA
levels <4 ng/mL
.

70. Does Prostate Cancer Treatment Prevent
Deaths?
•The value of surgery for localized disease was first assessed by the
Scandinavian Prostate Cancer Group- 4 (SPCG-4)
•median f/up of 12.8 yrs, the RP group had significantly lower overall
mortality (RR, 0.75; P = .007) and prostate cancer–specific mortality
•In contrast to the SPCG-4, the Prostate Intervention Versus
Observation Trial (PIVOT) and ProtecTtrial showed no significant diff
in both the arms

71. Prospective Randomized Screening Trials
•The PLCOCancer Screening Trial - 77,000 men,aged55 to 74 yrswere randomized
to receive annual PSA testing for 6 years or usual care.
•
At 13 years of follow-up, anonsignificant increase in cumulative prostate cancer
mortality was observed among men randomized to annual screening
•The European Randomized Study of Screening for Prostate Cancer (ERSPC) is a
multicentertrial did not show a reduction in prostate cancer–specific mortality

74. Screening Recommendations (AUA)
•They recommended against screening of men younger than 40 years, average- risk men aged 40 to
54 years, most men older than 70 years, and men with a life expectancy of less than 10 to 15
years.
•They recommended that screening decisions be individualized for higher risk men aged 40 to 54
years and men older than 70 years in excellent health.
•They placed primacy on shared decision making versus physician judgments about the balance of
benefits and harms at the population level.
•Even for men aged 55 to 69 years, the AUA concluded against screening
•The AUA recommends shared decision making for men aged 55 to 69 years, in whom they have
concluded the benefits may outweigh the harms.

75. OVARY screening
•Modalities proposed
1.bimanual pelvic examination
2.CA-125
3.TVU.
•The bimanual pelvic examination is subjective and not very
reproducible, but serum CA-125 can be objectively measured.
•CA-125 is neither sensitive nor specific.
•TVU has shown poor performance in the detection of ovarian cancer
in avg& high risk women.

76. PLCO trial
•78,216 average-risk women aged 55 to 74 years.
•Participants were randomized to receive annual examinations with CA- 125 (at
entry and then annually for 5 years) and TVU (at entry and then annually for 3
years) or usual care
•f/u for a max of 13 years, with mortality from ovarian cancer as the main study
outcome.
•conclusion -the number of deaths from ovarian cancer was similar in each group.

80. conclusion
•No organization currently recommends screening average-risk women for ovarian cancer.
•BRCA-Ovarian cancer screening—For carriers who have not undergone rrBSO, offer ovarian
cancer screening.
•TVS+CA125 every 6 months beginning at age 30 or 5 to 10 yrsbefore the earliest age of 1
ST
diagnosis of
ca ovary in the family
•a National Institutes of Health (NIH) consensus panel concluded that it was prudent for women
with a known hereditary ovarian cancer syndrome, such as BRCA1/2 mutations or HNPCC, to have
annual rectovaginal pelvic examinations+ CA- 125 +TVU(
until childbearing is completed )
or at least until age 35 years, at which time rrBSOis recommended