Screening – Cervical

Cancer
 Today’s discussion
• “Why”
• “What” do we achieve -Goals & Objectives
• “How” -Methods of screening
• “When” &
• “Whom” - Guidelines

• Low resource setting

• Management of CIN
India
1,23,907 – NEW CASES (3rd rank)

77,348 – DEATHS (2nd rank)

 Preventable Cancer
• Primary prevention - Vaccine
• Secondary prevention - Screening
• Long precancerous phase - Treatable
• Early stage --- better survival ?Cure

• India has 1/4th of cervical cancer related

deaths worldwide
 Methods
• Cytology - Pap smear – Conventional/LBC

• Visual methods
Visual Inspection with Acetic Acid (VIA)
Visual Inspection with Lugol’s Iodine (VILI)

• HPV detection
 CYTOLOGY VIA/VILI HPV
Sensitivity 47 - 62% 67 - 79% 66- 100%

Specificity 60 - 95% 49 - 86% 62 - 96%

Merits Triaging HPV + • Good method for “single
visit” approach
• HCW workers can do
• Most objective &
reproducible
• Very good for peri &
postmenopausal
women - high accuracy

De-Merits • Lot of • High FP rates (especially • Not recommended for

infrastructure and at the beginning of <30 (Young)
manpower training)
• Quality control • Unreliable in • High FP rates
issues postmenopausal women
• Not suitable for
“single visit”
approach
 Conventional LBC

Sensitivity 47 - 62% Similar

Specificity 60 - 95% Similar

Smear Unsatisfactory Rate High Low

Advantages & • Low cost • Costly but automated

Disadvantages • Overlapping smear • Monolayer smear
• High chance for artifact • No blood & mucus, air
dry artifacts
• Sample left for Anciliary
tests
 Specimen Collection

• At least 48 – 72 hours prior “Avoid”

Douching and tampons
Intravaginal Medications
Intercourse
Preferable to do after 2-3 days of stopping of periods

• During
No Lignocaine jelly
Sample both Ectocervix and Endocervix
No airdrying – fix immediately
 Visual inspection methods

• VIA - 3% - 5% acetic acid, freshly prepared, read at 1 minute

(Acetowhite areas)

• VILI - Lugol’s iodine, read immediately (Iodine negative areas)

Mahogany Brown Vs Mustard Yellow
• Most new HPV infections are cleared within 1 year by host immunity
• Persistent HPV infections - consequently positive results at least 12 months apart
• Women with persistent HPV positive tests - more chances of progression to high grade
lesions
 HPV Tests
• Detecting viral DNA - by PCR
- by Hybridization

• Detecting viral RNA - detecting mRNA for E6/E7 oncoproteins

• Detecting HPV at molecular level - p16 / Ki67 staining in cytology

and histopathology

• Uses - Primary screening by HPV test, Co-testing, Reflex testing

Stoler MH, Wright TC, Parvu V, et al. The Onclarity Human Papillomavirus Trial: design, methods, and baseline results. Gynecol Oncol. 2018;149:498-505.
(ROCHE COBAS)

Zhao C, Weng B, Li Z, Yang H, Austin RM. Follow-up outcomes of a large cohort of low-risk women with negative imaged liquid-based cytology and negative
HPV test results. Am J Clin Pathol. 2013;139:32-38. (BD ONCOCLARITY)
 Various HPV tests
Name of test Method utilized FDA approval

Digene Hybrid Capture 2 High Risk HPV types Cotesting & Reflex testing
(Available in TMH) Nucleic acid hybridization assay using
chemiluminescence

Cobas Roche(Available in HR HPV types; Primary HPV testing

India) type 16 & 18 are reported sepeartely Cotesting & Reflex testing
DNA PCR based

Cervista HR HPV DNA test Cotesting & Reflex testing

Cervista HPV 16/18 Signal amplification method

Aptima HPV assay mRNA of E6/E7 oncoproteins Nucleic acid Cotesting & Reflex testing
Aptima HPV 18, 18/45 amplification test

BD oncoclarity HPV DNA PCR based Primary HPV testing

Type 16, 18, 45 reported separately Cotesting & Reflex testing
Interim Clinical Guidance
Huh WK, et al. Gynecologic Oncology (2015)
 “Point of care” HPV tests
• Results are available in few hours

• Helps in reducing visits - “Single Visit”(screen & treat) approach

• CareHPV (available in India)and Xpert HPV

Estimating the value of point-of-care HPV testing in three low and middle income countries: a modelling study. Campos NG et al. BMC
Cancer 2017

New HPV-DNA test for cervical cancer screening in developing regions: A cross sectional study of clinical accuracy in rural china. Qiao YL,
et al. Lancet Oncol 2008 .
• Screening group - statistically
significant reduction in cervical
cancer mortality - 31% reduction
(RR - 0.69)

• Demonstrates the efficacy of an easily

implementable strategy that could
prevent 22000 cervical cancer deaths in
India and 72600 deaths in resource-
poor countries annually
Conclusion: HPV-based screening provides 60–70% greater protection against invasive
cervical carcinomas compared with cytology. Data of large-scale randomised trials support
initiation of HPV-based screening from age 30 years and extension of screening intervals
to at least 5 years(High NPV)
• In a low-resource setting, a single round of
HPV testing was associated with a
significant reduction in the numbers of
advanced cervical cancers and deaths from
cervical cancer.
 2005

• Cost effectiveness of different screening tests in 5 countries (including

India)
• Most effective - those with fewest visits

• “Once a lifetime” screening at the age of 35 years with “one-visit” or

”two-visit” screening strategies - VIA & HPV testing - reduced the lifetime
time risk of cancer by 25-36%
• “Two screenings” reduced the relative cancer risk by an additional 40%
 FOGSI GCPR 2018

• Different guidelines and protocols for Good resource and Low

resource setting

• Cotesting - Preferred method in 30-65 yrs

• Primary HPV testing - Acceptable method in 30 - 65 yrs

• Single visit approach should be practiced wherever possible -

minimize loss to follow up
• HPV testing - Best -
alone or in
combination with
cytology
• Centers with
established cytology
program with good
quality indicators -
continue to do same
• VIA - Suitable for low
resource setting
• Wherever possible
Colposcopy should be
used to obtain a
guided biopsy
• Else - biopsy can be
guided by VIA
• Start at 25 yrs / 30 yrs -
depending on resource

• Till 65 yrs

• In Low resource setting

VIA - every 5 yrs -
Target is to screen a
woman atleast 1-3
times in a lifetime
• No history of CIN2+ in last
20 yrs and previous
adequate negative
screening  stop at 65
yrs

• Post hysterectomy -
CIN2+ report - continue
screening for 20 yrs from
age of surgery
 Triage positive:

VIA
Genotype 16/18
>/=ASCUS-
 COLPOSCOPY

Triage Negative – F/U at 1yr

 HPV+/PAP –:Genotyping
HPV-/PAP+:ASCUS/LSIL-F/U 1yr
HSIL/ASC-H:COL
HPV+ : COLPOSCOPY
COLPOSCOPY
ASCUS/LSIL:Observe with close
surveillance or COLPOSCOPY
Individualized
COLPOSCOPY
 COLPOSCOPY
Mx:Case to case basis after d/w
pt
R/O Endometrial pathology
TVS/EB
AGC -Evaluate complete genital
tract
COL/TVS/EB/ECC
 Repeat
HPV preferred
VIA+ : COLPOSCOPY or See&Rx
IARC manual
 Screening in pregnant women
• Pregnant women should undergo speculum examination at
the first visit.

• If grossly cervix is normal  defer screening till postpartum

period (6 weeks)

• If speculum examination is abnormal  follow screening

protocols
• Recommended age to start screening - 30 years

• Priority age group is 30 - 49 years

• Screening even “once in a lifetime” – BENEFICIAL

 SINGLE VISIT APPROACH

• WHO recommends - depending on availability of resources –

Screen with HPV test and Treat with Cryotherapy

OR
Screen with VIA and treat with Cryotherapy or LEEP.

• Treated women - post treatment follow up at one year to ensure effective treatment

• Single round of screening in women > 35 yrs 25% reduction in life time risk of cervical
cancer

Goldie SJ, Gaffikin L, Goldhaber-Fiebert JD, Gordillo-Tobar A, Levin C, Mahe C, Wright TC. Cost effectiveness of cervicalcancerscreening in five developing countries. N Engl
Med. 2005;353 (20):2158–68
Vet JNI, Kooijman JL, Henderson FC, et al. Single-visit approach of cervical cancer screening: See and Treat in Indonesia. British Journal of Cancer. 2012;107(5):772- 777.
doi:10.1038/bjc.2012.334
Sankaranarayanan R, Nene BM, Shastri SS, et al. HPV screening for cervical cancer in rural India. N Engl J Med 2009; 360: 1385–94.