SCREENING FOR MALIGNANCIES

2

OBJECTIVE

Concept of preventive oncology,

screening and early detection

3

EXPECTED OUTCOME

Standard methodologies for screening

Cancer cervix, breast, uterus, ovaries, others

4

SCREENING FOR MALIGNANCY

Genital Cancers

Cervix, Endometrium, Ovary

Others

Breast, Colorectal, Oral

5

CANCER CERVIX

Commonest cancer in Indian women

Third commonest in the world

Annual global incidence : 500,000

India contributes 100,000 (1/5th)

Every year world wide 200,000 women die

Magnitude more than evident

6

Opportunities For Cancer Control Interventions

7

7

Communicating Effectively With Parents and Patients

Include HPV vaccines in discussion of all vaccines

recommended for adolescents

Use a short, matter-of-fact approach to HPV vaccine

recommendation

Emphasize cancer prevention

8

Strategies for Increasing HPV Vaccine Uptake

The strongest predictor of a person being vaccinated is a physician recommendationa

Have the conversation!

Educate yourself to educate parents and patients about vaccines

Most parents want to vaccinate their children

Discuss all adolescent vaccines before they are due

Address parents’ questions

Questions may reflect interest rather than vaccine refusal

Immunize at every opportunity

Offer the HPV vaccine when other vaccines are being administered

8

a. Nichol KL. Cleve Clin JMed. 2006;73:1009-1015

9

SCREENING FOR CA CERVIX

No organised screening programme in India

Recommended in:

Sexually active women over 30 yrs

Sexually active for more than 10 yrs

10

SCREENING METHODS

VIA

VILI

Cervical Smear from Ecto & Endo Cx

HPV testing whenever possible

Introduce Colposcopy when possible

11

PAP TEST (CERVICAL / VAGINAL CYTOLOGY)

Uses

Screening and diagnosis of CIN

Detection of Genital infection

Evaluate Hormonal status

For additional information regarding cytology follow-

up a gynecologist should be consulted

12

Cells of the Cervix

13

The Bethesda system 2001

Negative for Intraepithelial Lesion or Malignancy

Infection

– Trichomonas vaginalis

– Fungal infection such as Candida species

– Bacterial vaginosis

– Actinomyces species

– Herpes simplex virus

Other findings

– Reactive cellular changes;

– Inflammation (includes typical repair)

– Radiation effects

– Intrauterine contraceptive device

– Glandular cells present after hysterectomy

– Atrophy

14

TBS 2001

Epithelial Cell Abnormalities

Squamous cells

Atypical squamous cell of undetermined significance (ASC-US)

Atypical squamous cell cannot exclude HSIL (ASC-H)

Low-grade squamous intraepithelial lesion (LSIL)

High-grade squamous intraepithelial lesion (HSIL)

Squamous cell carcinoma

Glandular cells

Atypical glandular cells (AGC) (specify endocervical, endometrial, or not otherwise specified)

Atypical glandular cells, favor neoplastic (specify endocervical or not otherwise specified)

Endocervical adenocarcinoma in situ (AIS)

Adenocarcinoma

Other

Endometrial cells in a woman ≥40 years of age

15

15

Population†

 USPSTF ( us preventive task force) 

ACS/ASCCP/ASCP( ameirican cancer society, american socieity of colposcopy and cervical pathology, american society for clinical pathology)

Younger than 21 years 

Recommends against screening.Grade: D recommendation.

Women should not be screened regardless of the age of sexual initiation or other risk factors.?

21–29 yearsRecommends screening with cytology every 3 years. Grade: A recommendation.

Screening with cytology alone every 3 years is recommended. 

30–65 years

Recommends screening with cytology every 3 years or for women who want to lengthen the screening interval, screening with a combination of cytology and HPV testing every 5 years. Grade: A recommendation.

Screening with cytology and HPV testing (“co-testing”) every 5 years (preferred) or cytology alone every 3 years (acceptable) is recommended.

HPV vaccinatedWomen who have been vaccinated should continue to be screened.

Recommended screening practices should not change on the basis of HPV vaccination status.

MARCH 14 2012 Recommendations for Cx. Cancer screeningModified from CA Cancer J Clin. 2012;62:147-172 .

04/15/2023

Older than 65 years 

Recommends against screening women who have had adequate prior screening¶ and are not otherwise at high risk for cervical cancer. Grade: D recommendation.

Women with evidence of adequate negative prior screening¶ and no history of CIN2+ within the last 20 years should not be screened. Screening should not be resumed for any reason, even if a woman reports having a new sexual partner.

After hysterectomy 

Recommends against screening in women who have had a hysterectomy with removal of the cervix and who do not have a history of a high-grade precancerous lesion (ie, CIN 2 or 3) or cervical cancer.Grade: D recommendation

Women of any age following a hysterectomy with removal of the cervix who have no history of CIN2+ should not be screened for vaginal cancer. Evidence of adequate negative prior screening is not required. Screening should not be resumed for any reason, including if a woman reports having a new sexual partner.

high-risk populations who may need more intensive or alternative screenin. These special populations include women 1) with a history of cervical cancer, 2) who were exposed in utero to diethylstilbestrol (DES), and 3) who are immune-compromised (eg, infection with human immunodeficiency virus).

16

17

WHO RECOMMENDATIONS

Cytology is recommended for large-scale cervical cancer screening if sufficient resources exist

New programmes should start screening women aged 30 years or more, and include younger women only when the highest-risk group has been covered

Existing organized programmes should not include women less than 25 years of age in their target populations.

If a woman can be screened only once in her lifetime, the best age is between 35 and 45 years

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How to take a Pap Smear ?

Patient in dorsal position

Good illumination is necessary

Cusco’s speculum is inserted to visualise & fix the cervix

Inspection of cervix done & findings are noted

Ayres spatula is inserted first. It is placed at cervical os so that longer end goes into cervical canal and smaller end rests on ectocervix

19

How to take a Pap Smear

Spatula is rotated through 360 degrees maintaining contact with ectocervix

Do not use too much force [bleeding /pain]

Do not use too little force [inadequate sample]

Sample is smeared(both sides of spatula) evenly on the slide and fixed immediately

20

How to take a Pap Smear

Endocervical sample is collected using

an endocervical brush

Insert the cytobrush into canal, so that

last bristles of brush are visible

Rotate the brush through 180 degrees.

[ more rotations increase the chance of

bleeding ]

Sample is rolled on the slide and fixed .

21

FIXATION OF SMEAR

Fixation is done immediately with fixative like 95% alcohol or cytofix spray to avoid air drying

Spray should be kept at 10 inches, to avoid destruction of cells by propellent in the spray

Smear should be monolayer for proper penetration of cell surface by fixative

22

Interpretation Of PAP’S Smear

In menopausal women not taking estrogen replacement therapy, the presence of endometrial cells is an abnormal finding and should be followed up with an endometrial biopsy to try to determine the reason for the presence of these cells.

Koilocytosis This finding is often based on the presence of "koilocytes" having enlarged nuclei, surrounded by a clear "halo" of cytoplasm. Koilocytes often (but not invariably) point to the presence of of human papilloma virus (HPV) in the cells.

23

Interpretation Of PAP’S Smear

Inflammation merely means the cervix is irritated for some

reason. In the absence of any symptoms or any other significant

abnormality on the Pap, it can be safely ignored.

If inflammation is severe enough, it may interfere with the ability

of the cytologist to accurately read the Pap. In such cases, it is wise

to repeat the Pap at more frequent intervals (6-9 months) rather

than the usual once a year.

Inflammation by itself need not be treated. If other abnormalities

are identified in addition to the inflammation, you may treat the

other problems and the inflammation will probably go away.

24

CERVICAL SMEAR

Percentage reduction in Invasive Ca

– Annual : 93%

– 3 Yrly : 91%

– 5 Yrly : 84%

False Pos : Rare False Neg : 10-35%

Specificity : 94% Sensitivity : 52%

Shortcomings

25

LIMITATIONS

Difficulty in preserving & transporting

Lack of trained technicians to analyze

Problems in getting women back for results, follow-up,

referral, and treatment when necessary.

26

VIA

Speculum exam

Application of 3-5% acetic acid

Viewing the cervix with the naked eye to identify

colour changes

Abnormal tissue appears white

Positive, Negative or Suspicious for cancer

27

VIA RESULTS

NEGATIVE POSITIVE

28

VIA RESULTS

SUSPICIOUS FOR CANCER

29

STRENGTHS OF VIA

Simple, easy-to-learn approach

Low start-up & sustaining costs

All types of health care providers can perform test

Results available immediately

Possible to integrate VIA into PHC

30

LIMITATION

Post menopausal women

Not suitable as SCJ inside canal

Results not as reliable

IMS Clinical Practice Guidelines on Menopause 2013

31

HPV

Primary cause of cervical cancer

Most women with high-grade CIN have detectable HPV DNA

HPV positive, Pap smear normal women are at increased risk of CIN

Lorinz A et al. Human papilloma virus infection of the cervix. Relative risk association of 15 common anogenital types. Obstet Gynecol 2000, 79:328-337

32

HPV DNA CERVICAL SAMPLERand LBC Sampler

33

Low Risk + or HPV–

ASCUS

HPV TEST

HPV +

Repeat Pap and/or HPV Test in 6 mo. or return to routine screening at discretion of clinician

COLPOSCOPYBIOPSY / ABLATION

HPV TRIAGE FOR ASCUS

34

STRENGTHS OF HPV

High-risk HPV DNA testing

For triage management of post-menopausal women

with unequivocal cytology results

Once in 5 yrs till age 65

IMS Clinical Practice Guidelines on Menopause 2013

35

LIMITATIONS OF HPV

High cost

Not easily available

Lower specificity than cytology

Samples to be sent to a special lab

Follow-up visit required for report

36

INDICATIONS FOR COLPOSCOPY

HSIL or Invasive Ca on Smear

Persistent LSIL on Smear

Positive VIA / VILI

Positive HPV DNA test

LSIL in a non compliant woman

Suspicious looking cervix

Therapeutic

37

CIN as Seen in Colposcopy

CIN 1: Mild dysplasia; includes condyloma (anogenital warts)2

CIN 2: Moderate dysplasia2

CIN 3: Severe dysplasia; cancer in situ (CIS); FIGO Stage 02,3

CIN 1 CIN 2 CIN 3

1. Wright TC Jr, Cox JT, Massad LS, et al, for the ASCCP-Sponsored Consensus Congress. JAMA. 2002;287:2120–2129. 2. Bonnez W. In: Richman DD, Whitley RJ, Hayden FJ, eds. Washington, DC: American Society for Microbiology Press; 2002:557–596. 3. Canadian Cancer Society. Cervical Cancer: What you need to know. Available at: http://www.cancer.ca/vgn/images/portal/cit_86751114/63/40/151140772cw_library_wyntk_cervical_en.pdf. Accessed March 13, 2006. 4. Reprinted with permission from Sellors JW, Sankaranarayanan R, eds. Colposcopy and Treatment of Cervical Intraepithelial Neoplasia. A Beginner’s Manual. Lyon, France: International Agency for Research on Cancer; 2003.

Photo courtesy of Dr. J. Monsonego Photo courtesy of Dr. J. Monsonego From IARC, 2003.4

Colposcopy findings confirmed by histology1

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BREAST CANCER : INDIA

28/100,000 Urban, 6/100,000 Rural

More than doubled over last 20 yrs

100,000 new cases annually

43 - 46 years

Late marriage, small families

Shorter lactation

Obesity

39

BREAST CANCER

Breast self examination monthly

Clinical exam annually

Annual mammograms from age 40

High risk screening to start 10 yrs earlier than

youngest affected family member

40

BREAST SELF-EXAMINATION

A women checks her own breasts & can look for

irregularities, lumps, changes in breast size or shape,

nipple discharge, or irregular tissue thickening.

Not much data to show a statistically significant

reduction in detection of breast cancer

However in India, increases awareness and may detect

and downstage the cancers

41

CLINICAL BREAST EXAMINATION

A clinical breast examination (CBE) is a physical examination of

the breast performed by Clinician.

Aim – main goal of CBE is to differentiate normal physiologic

nodularity from a discrete breast mass If a discrete mass is

identified , evaluation in this case is mandatory to exclude breast

cancer. CBE is able to identify 10 to 25% of breast cancer which

are missed by mammography . Specificity of CBE is 85 to 99% but

Predictive value is its major limitation. Lesion detected by CBE

only 6 to 46 % are malignant depending on the age of the patient.

42

MODALITIES OF BREAST IMAGING

USG

Mammography

MRI

43

USG

Commonly used in young females

Increases the sensitivity of mammography

Operator dependent

Not approved for screening

Useful to distinguish solid from cystic lesions

Useful in guiding aspiration and biopsies

Findings suspicious of malignancy on usg- solid mass, irregular, taller than wider, > 4 lobulations

44

MAMMOGRAPHY

Highly sensitivity, older women

Findings suspicious of malignancy-

Irregular, spiculated mass

Clustered microcalcifications (< 5 mm in diameter)

Solid mass with ill defined borders

Architectural distortion

Enlarging, solid well circumscribed mass

Focal asymmetric density

Enlarged axillary nodes with loss of architecture

45

BREAST CANCER SCREENING

Screening by mammography results in reduction of

mortality by 30% in women> yrs.

Mammographic screening programme is not

sustainable in developing countries.

Physical Examination of breast by trained personnel

has sensitivity of 75% and specificity of 90%.

BSE may help but there is no evidence that it improves

survival.

46

MALIGNANCY LEFT BREAST

47

MAGNIFICATION VIEW

48

USG OF MALIGNANT LESION

49

MRI BREAST

Dedicated breast coil

Highly sensitive, poorly specific

Leads to unnecessary biopsies

Does not visualize calcifications

Has no place in routine evaluation of breast lumps

50

MRI BREASTOnly indications-

Occult primary with positive axillary nodes

To distinguish scar from recurrence in operated breast cancer patients

Residual tumour- positive margins

Invasive lobular carcinoma

To know extent of disease – multifocal/ multicentric

Contralateral cancers

Discordant clinical exam, mammography/ usg findings

Implants

Screening of high risk women

51

ENDOMETRIAL CANCER

No screening programme : opportunistic

Categorize the high risk group and counsel

Pap Smear : Sensitivity 40%

USG : TAS : No Value

TVS : Effective, non-invasive

52

Risk of endometrial cancer

Obesity,

Nulliparity,

Hypertension,

Diabetes,

Polycystic ovarian syndrome,

Endometrial hyperplasia,

Early menarche,

Late menopause,

Unopposed estrogen therapy,

Family history of cancer, past history of breast cancer and

Tamoxifen therapy

53

Risk of endometrial cancer

Decreased by Prolonged use of OCPs and

progestins.

Reduced risk by HRT specially in obese women

54

ENDOMETRIAL THICKNESS

Post-menopausal Bleeding

Must investigate promptly

ET : > 4mm

Sensitivity : 96% for Endo Ca

HT : 4mm

Tamoxifen : 8mm

55

Interpret the findings

4x4cms

What is the incidence of Endometrial Ca at 50 yrs?

56

Pipelle

Sensitivity in detecting

Endmetrial caner ?

What percentage need

further investigation?

57

OVARIAN CANCER

No effective screening

No recognised pre-invasive stage

Inaccessible for visualisation or sampling

60-70% diagnosed in Stage III

58

Risk factors for ovarian cancer

Increasing age,

Nulliparity,

Use of fertility-enhancing drugs such as clomiphene

citrate for more than 1 year,

Family history of ovarian, breast or colorectal cancer,

and past history of breast cancer.

Obesity might increase some types but not all, whereas

59

Decreased risk of ovarian cancer

Use of oral contraceptive pills is a very potent way to

decrease ovarian cancer risk.

Certain gynecological surgeries like tubal ligation,

hysterectomy and cure of endometriosis are protective

against ovarian cancer

Exercise could help to decrease the risk

60

OVARIAN CANCER

CA 125

> 35u/ml in 80% Epithelial cancers

Raised in Endometriosis, PID, Koch’s

Other tumour markers: CA602 & CA546

TVS

Colour Doppler

61

STOMACH CANCER

In women aged 30–69 years, the second most common fatal cancers was stomach (14.1%). Stomach cancer rates were higher in rural than in urban areas of India due to increased prevalence of chronic H. pylori infection.

Million death study cancer mortality in India: a nationally representative survey 2012. This may include stomach and primary liver cancer.

Prevalence of hepatitis B virus in India was less than 1.9% in 72,000 pregnant women aged 15–49 years who were tested in 2002.

Million death study 2012

62

PREVENTION

Thirty seven percent of all female cancer deaths were from infection-related cervical, stomach, and liver cancers and 18.3% were from tobacco-related cancers.

This underscores the importance of vaccination, control of infection.

Vaccination against hepatitis B virus would reduce future liver cancer deaths and cirrhosis.

Use of tobacco in pan and beedi should be strongly discouraged.

IMS Clinical Practice Guidelines on Menopause 2013

63

HBV Screening Algorithm for At-Risk Patients

HBsAg and anti-HBS test

HBsAg +

HBsAg -

Anti-HBs +

Anti-HBs -

Collect baseline data • ALT • HBeAg, anti-Hbe • HBVDNA level and • Go to evaluation and

monitoring algorithm

Immune to HBV, no follow-up needed

HBV Evaluation and Monitoring Algorithm

LokASF, et al. Hepatology. 2009:50:1-36

Vaccinate

64

ORAL CANCER

Oral examination every 3 years

High risk group annually

Detect precancerous lesions

65

COLORECTAL CANCER

50 years

Stool for occult blood annually

5 yearly: Flexible sigmoidscopy or

Double contrast Barium enema

Colonoscopy every 10 years

66

Preventive strategies for all cancers

Stop smoking

Control weight

Exercise (vigorous exercise for at least 2–3 h/week)

< 15 g/day alcohol intake

Diet rich in vegetables, fibers and fruits (five fruit and

vegetables/day but only two fruits, maximum three),

low intake of animal fat, and a low proportion of

carbohydrates

67

When should women report

Abnormal vaginal bleeding, abdominal or pelvic pain, distension, abnormal vaginal discharge, hematuria, or rectorrhagia can reveal an endometrial, ovarian or colon cancer.

Breast nipple discharge or palpation of a lump, induration of a localized zone of the breast, a skin abnormality on the area of the breasts (skin or nipple retraction, 'peau d’orange') can indicate breast cancer.

Unusual cough, dyspnea, hemoptysis or thoracic pain can reveal a lung cancer.

Occurrence of venous thrombosis in women without a family history can reveal a cancer and needs some complementary investigations.

68

CASE

51 yr old, post menopausal 3 yrs

Routine screening

Smear : LSIL

Refd for management

What would you advise?

Vaginal estrogen for 1 month and rpt

Anxious, refer for Colposcopy

69

70

CASE

Smear : HSIL

What would you do?

Refd for Colposcopy

71

72

What would you do?

LLETZ

HPE : HSIL

Follow up?

Smear after 6 mths : Normal

Smear after 12 mths : ASC-H

Advise?

Rpt Colposcopy

73

74

Diagnosis?

Healed cervix after LLETZ

Rpt Smear after 12 months

75

CASE

45-year-old P2 complains of amenorrhea one year with 15-20 hot flashes/day

History of Lt radical mastectomy for breast cancer 7 years ago with complete cure

BP 130/85, Wt 60 kg. Ht 163cm

Right Breast, abdominal & pelvic examinations revealed no abnormal findings

Fasting sugar 95 mg/dl & lipid profile WNL

Treatment?

76

TREATMENT

For hot flushes

Non-hormonal : Lifestyle modification

Venlaflaxine 37.5 mg twice a day

For Osteoporosis

Bisphosphonates and others

77

BREAST CANCER SURVIVORS

Inc incidence of Ca Breast

Improved survival times after treatment

Induce early menopause & climacteric symptoms

More breast cancer survivors with vasomotor

symptoms

78

Hormone Therapy and Breast CancerEstrogen Alone

Estrogen alone increases percentage mammographic density, not as much as estrogen and progesterone together (Level A).

Estrogen increases the risk of breast cancer after more than 5 years of use, particularly in recently postmenopausal women (Level B).

The attributable or excess risk for 5 years usage is 0/1000 to 2.59 per 1000 (Level C).It falls under the rare category.

Increased risk dissipates within 5 years of discontinuing the HT (Level B).

Tumors in HT used women are usually ER positive and lobular type (Level C).

IMS Clinical Practice Guidelines on Menopause 2013

79

Hormone Therapy and Breast CancerEstrogen + Progesterone

E + P increases percentage mammographic density significantly (Level A).

E + P particularly with synthetic progesterones increases the risk of invasive breast cancer within 3–5 years of initiation and increases progressively beyond that time (Level B).

Emerging data from 2 independent studies report that micronized progesterone/dydrogesterone does not increase the risk if given for less than 5 years (Level C).

The risk returns to approximately that of non-users within 3 years of cessation (Level B).

IMS Clinical Practice Guidelines on Menopause 2013

80

BREAST CANCER SURVIVORS

Consider HT in some women whose quality of life

impaired by estrogen deficiency, after adequate

counselling

Risk of recurrence must be explained

Fair trial with alternative therapies given prior to

starting HT/Tibolone

Lowest effective dose for shortest duration

81

All these are possible with screening except

a) Early detection of disease

b) Improving the treatment results

c) Decreasing mortality due to disease

d) Eradication of disease