The document discusses various options for cervical cancer screening including conventional Pap smears, liquid based cytology, and several HPV testing assays. It emphasizes that HPV testing is more sensitive than cytology alone in detecting cervical lesions. HPV co-testing or HPV testing alone are recommended, with triage of positive HPV tests by genotyping. Liquid based cytology allows for both cytology and HPV testing from a single sample. Algorithms are provided for HPV testing in primary screening and for cytology with HPV co-testing. A table compares the available cervical cancer screening tests offered.

1. Dear Colleague,
We offer a suite of diagnostic options for cervical cancer screening. These options include the following:
• Conventional Pap Smear
• Liquid Based Cytology (LBC) – BD SurePath
• HPV PCR Assay – Seegene Anyplex II HPV HR Detection
• HPV HC2 Assay – Digene HC2 HPV DNA Test
• Cervical Self Collection – Delphi Screener (used in conjunction with Digene HC2 HPV DNA Test)
At Quantum, we seek to support and empower doctors through education and by providing the necessary diagnostic tools to
help you make more informed decisions for patients. This article aims to do that by providing you with the latest update on
the increasingly important role of HPV screening in cervical cancer detection and prevention. We believe that to remain
relevant and to help you deliver the best outcomes for patients; we have to continue to innovate and to bring you the most
up to date in actionable diagnostic tests.
Cervical cancer is the third most common cancer in Malaysian women (Malaysia National Cancer Registry Report 2007). 45%
of cases reported were diagnosed at Stages 3-4 which means poorer outcomes and lower survival rates. The expected 5 year
survival rate of patients diagnosed with Stage 4 Cervical Ca is 15%. This survival rate rises to almost 90% in patients diagnosed
at Stage 1. This highlights the importance of early detection in ensuring patients have a better chance of survival.
The introduction of cervical cancer screening programmes and HPV vaccination has not achieved the desired effect of
reducing our cervical cancer mortality rates. There are a number of factors for this, including poor coverage by the national
screening programme as well as very poor recall rates following baseline screening. Our national mortality rate from cervical
cancer remains high at 4.7 ASR deaths per 100 000 (Globocan 2012) – almost double that of Singapore at 2.6 ASR deaths per
100 000. This huge difference in our mortality rates mean that there is still much that can and needs to be done.
The causal association of persistent HPV infection and the development of cervical carcinoma is well established. This
association together with the strong evidence base for HPV as an accurate screening tool is the reason why HPV co-testing has
been introduced into the national screening programmes of Australia and the Netherlands. As more and more studies
continue to add strength to the evidence base of HPV screening in cervical cancer detection, we will continue to see this trend
grow.
Based on the current evidence available, our key messages are as follows:
1. HPV co-testing significantly increases the detection of CIN2+ lesions at screening compared with cytology alone.
Co-testing (vs cytology alone) resulted in a significant 40% increase in detection of CIN2 lesions or worse – early
detection of premalignant CIN allows early monitoring and treatment to prevent disease progression.1
2. HPV testing alone is more sensitive than cytology alone in the detection of CIN 3+ lesions.
HPV testing alone has a 76.1% test sensitivity vs cytology alone which has a 46.8% test sensitivity. The specificities of
both tests are similar.2,3
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2. 3. Triage of positive tests by genotyping (into high and low risk genotypes) strikes an appropriate balance between test
utilization and safety. This increases detection rates of premalignant lesions without increasing unnecessary patient
referrals for colposcopy. ,3
4. HPV testing is significantly more accurate than repeat cytology at triaging patients with ASCUS following cytological
screening. HPV testing produced higher pooled sensitivity with similar specificity – therefore is a useful tool in decision
making when using cytological screening for cervical cancer.4
5. Liquid based cytology as a means of specimen collection allows for both cytology and HPV testing
Please find our suggested algorithms to guide decision making for HPV testing for primary cervical cancer screening and
Cytology with HPV co-testing. Also enclosed is a table of comparison of our available cervical cancer screening products to
guide patient decision making.
ASCUS - Atypical Squamous Cells – Undetermined Significance
CIN – Cervical Intraepithelial Neoplasia
References:
1. Co-testing for detection of high-grade cervical intraepithelial neoplasia and cancer compared with cytology alone: a meta-analysis of randomized controlled
trials. Bouchard-Fortier et al, J Public Health (Oxf). 2014 Mar;36(1):46-55. doi: 10.1093/pubmed/fdt057.
2. Primary cervical cancer screening with human papillomavirus: End of study results from the ATHENA study using HPV as the first-line screening test. Wright et al,
Gynecol Oncol (2014), http://dx.doi.org/10.1016/j.ygyno.2014.11.076
3. Use of primary high risk human papillomavirus testing for cervical cancer screening: Interim clinical guidance. Huh et al, Gynecol Oncol (2015),
http://dx.doi.org/10.1016/j.ygyno.2014.12.022
4. Human papillomavirus testing versus repeat cytology for triage of minor cytological cervical lesions. Arbyn et al, Cochrane Database Syst Rev. 2013 Mar
28;3:CD008054. doi: 10.1002/14651858.CD008054.pub2.
• Seegene HPV PCR uses multiple real time PCR technology to detect and identify 19 high-risk HPV genotypes (including HPV 16 and 18) and 9 low-risk HPV
genotypes
• Digene HPV Test uses Hybrid Capture 2 (HC2) technology to test for 13 high-risk HPV genotypes (including HPV 16 and 18) and 5 low-risk genotypes
Disclaimer of Medical Liability
Quantum Diagnostics Sdn Bhd and the author are not responsible or liable for any advice, course of treatment, diagnosis or any other information, services or
products that an individual obtains through this document. This document is not for use in medical emergencies and users should exercise their own clinical
judgment in their practice.
Produced by Dr. Tan Shih Yang, Medical Affairs
sytan@quantumdxs.com

3. HPV Testing
Cytology - HPV Co-testing
Repeat HPV
testing in 3 years
Positive
Colposcopy
Repeat HPV
testing in
12 months
Triage by Cytology
Triage by HPV Genotyping
Atypical Squamous Cell -
Unknown Significance
(ASC-US)
HPV 16/18 Positive
Other HrHPV
Positive
Negative for Intraepithelial
Lesion or Malignancy
(NILM)
Negative
Routine
screening in
3 years
Repeat
Co-testing
12 Months Colposcopy
Cyto-ve
HPV-ve
Cyto-ve
HPV+ve
Cyto ASC-US/LSIL
HPV-ve
Cyto ASC-US/LSIL
HPV+ve
Suggested algorithm for Cytology with HPV Co-testing
Suggested algorithm for HPV testing as
Primary Cervical Cancer Screening

4. TABLE OF COMPARISON: CERVICAL CANCER SCREENING TESTS
Conventional
Pap Smear
Method
of collection
Collection done with spatula/brush
and placed on slide for analysis
Collection done with brush and
placed in preservation solution
for analysis
Self-collection done with
Delphi Screener device
and sent for analysis
• Conventional technique – familiar
to patient/doctor
Cytology only
RM 70
3 days 10 days
Cytology or HPV (or both)
RM 120 (Cytology alone)
RM 400 (HPV PCR alone)
RM 500 (Cytology + HPV PCR)
3 days (Cytology alone),
10 days (including HPV PCR)
Advantages
Disadvantages
Test Type
Recommended Price
Turnaround Time (TAT)
SurePath
(Liquid Based Testing)
Delphi Screener (Vaginal
Self-sampling) + Digene HPV Test
• Smaller proportion of cells captured
resulting in less representative
sample
• Collected sample can only be
tested for cytology
• High rate of repeat collection due to
inadequate samples, air drying
artefacts, overlapping material and
debris
• More expensive than conventional
Pap Smear
• Sample can be used for both
cytology and HPV testing – refer
algorithms
• Almost all collected cells captured
– more representative sample for
analysis
• Lower rate of inadequate samples
(vs conventional Pap) - less repeat
collections
• Minimises air drying artefact,
obscuring, overlapping cellular
material and debris (common
problems with conventional Pap)
• Easier collection for practitioner
• Self-collection – done at patient
convenience and does not have to
be performed in a clinical setting
• Minimally invasive – does not
require speculum insertion
• Collected sample can only be used
for HPV testing
HPV only
RM 425