Pap, ASCUS, and HPV testing
On hearing that your Pap smear or HPV test is positive,
you need to avoid any angry confrontations with your doctor! The
ancient Greeks were known to kill the messenger who brought bad
news. True, your doctor may be giving you some upsetting news;
but, he/she did not cause your situation! Calm down!
If you blew up at your doctor because of this news, send him/her
a note of apology. He/she is there to HELP you. [how
you caught your HPV]
First of all, in today's litigeous climate, the medical system MUST be almost overly sensitive to any Pap smear finding which seems (is visually interpreted) "not quite right"..."a little unusual"..."atypical"..."not quite normal"..."abnormal". That is, there is a shade of gray between "normal" and "abnormal". In the 1970s, that gray zone was considered trivial and was diagnosed as "class II Pap, probable inflammatory change". Today, if there is any finding which is not strictly "typical" (that is, it is "atypical"), then a decision is made to either (1) "follow" the patient or (2) reflexly determine...using residual lquid specimen from that Pap smear sample...the "HPV status" by doing an HPV test (there are a number of different ways to test).
Less than 5% of women
infected with HPV who receive no medical intervention ultimately
develop cervical cancer3.
A high percentage of women under 30 who get HPV have body systems
which can clear the virus within about 2 years.
There are more than 100 virotypes of HPV & approximately
50 of these commonly infect the urogenital tract3.
Since cancer of the uterine cervix is so strongly associated with
HPV, there is a developing view that there are total-system efficiencies
and cost savings if the HPV-test status can be known in women with
a "not normal" (ASCUS, ASC-US, or SAUS or AGUS) Pap smear
report (or HPV high-risk clinical situation). In an average practice,
about 5-6% (some give a national average of 3%2)
of Pap cases are "not normal'. So, many of our doctors want
us to "reflexly" test for at least the high risk group
of HPV. As a rule (and theoretically...theory being that HPV causes
all squamous cancers of the cervix), cases with a precancerous
Pap or biopsy diagnosis of "dysplasia" will be already
be HPV-test positive (therefore no need to test). But, low and
high risk HPV-test groups can be HPV-test negative if there is
only a very small area of cervix dysplasia...such a small area
not providing sufficient HPV-virus-containing cells (in the Pap
sample) to trigger a positive test result. And, there may actually
be some cases of cervical dysplasia in which HPV is never demonstrated.
Liquid-based Pap smear specimens (SurePath [AutoCyte]
or ThinPrep) have set up a situation where the HPV test can be
done out of the residual specimen, thereby saving the patient another
office visit. The HPV testing might be ordered regardless of the
Pap smear result if the physician and patient consider that there
is an elevated risk that she harbors HPV. Otherwise, the HPV test
may be reflexly performed if the Pap smear interpretation is in
that borderline zone referred to as ASCUS/SAUS/AGUS. Reflex HPV testing is considered advantageous for triage of these cases in women aged 20 or older8. Currently,
the ratio of ASCUS cases that turn out to be any degree of SIL
(squamous intra-epithelial lesion) is about 1.7-1.9.
Stated conservatively, about 50,000,000 Pap smears
are performed each year in the USA, and about 4% are interpreted
as ASCUS/SAUS (2,000,000 cases per year).
Initial 2001 findings1 from
the National Cancer Institute's ALTS review (ASCUS/LGSIL Triage Study)
showed that the hc2 method reflex testing of about a third of 3488
participating patients found that HPV molecular testing was 96.3%
sensitive for detecting CIN III or higher. [go
to NCI and drop ALTS into
the site search engine] And, it could alternately be said
that high risk HPV negativity gives 99.5% certainty that the patient
does not have HGSIL or worse.
The American Society of Colposcopy and Cervical Pathology
(ASCCP) met 9/2001 & has
published recommendations relative to ALTS in the 24 April, 2002,
issue of JAMA4 recommending that atypical squamous
cells be divided into (a) those that are ASC-US and (b) those that
are ASC-H (ASC, cannot exclude high-grade dysplasia) & that
cases be followed up for clarification of significance of each
case by one of 3 methods:
|2002 ASCCP TRIAGE GUIDES:
2006 ASCCP TRIAGE UPDATES8:
repeat Pap smear in 4-6 months & to colposcopy & biopsy
if dysplasia detected & repeat at a second interval if first
was non-dysplastic...for ASC-US only.
proceed to colposcopy and biopsy...for ASC-H, ASC-US,
LGSIL, HGSIL, and AGUS (atypical glandular).
HPV testing triage...for ASC-US only (...see publications
area of Dr. Bolick's site
- continue to use 2001 Bethesda terminolgy.
- use a two-tiered grade for histology: low grade (CIN1) & hi-grade (CIN2-3).
- attempt to two-tier grade in ECC specimens.
- follow CIN1 for up to 2 years without treatment.
- in adolescents, separate CIN2 & CIN3 if you can...CIN2 is initially followed conservatively.
Our lab (as of 14 Oct. 2001) utilizes the SurePath
(AutoCyte) liquid-based Pap sample processor (which
we consider superior to ThinPrep). Our pathology group signed,
on 11 Oct. 2001, the commitment to obtain and utilize the
AutoPap (FocalPoint) artificial intelligence computer image
analysis screener which is applied to all of our Pap cases...followed
by manual rescreening of all cases by our cytotechnologists. Our
cytotechnologist-and-pathologist team has parallel data to show
that their detection performance is equally good whether working
with cytopreps made by old-style conventional methods or the liquid
based SurePath (AutoCyte) method. With that manual team plus supplementary
computer screening, we intend to find all of the "abnormals" displayed/contained
on the cytoprep slides. That will insure maximum detection of ASCUS/SAUS/AGUS
or cancer. Then we will send cases for HPV testing as indicated/requested
(individually or by standing order) by the physician. The ALTS
thought in 2003 that HPV-only primary cervical screening was reasonable
for women over 306.
Prior to 1 Feb. 2003 (when we began our own in-house
testing), we sent liquid Pap samples
to Molecular Pathology Laboratory in
Maryville, Tenn. for the Digene (Digene Corp. maintains an HPV
web site) Hybrid Capture 2 (hc2) signal-amplification
DNA cocktail assays (CPT code 87621). Lexington Medical Center
currently performs this Digene test in-house:
low risk panel: HPV 6, 11, 42, 43, and 44
high risk (oncogenic) panel: HPV 16, 18, 31,
33, 35, 39, 45, 51, 52, 56, 58, 59, and 68 (the
five that are bolded account for 80% of cases of cervical dysplasias
and cancers3)...with 16 & 18 being by far the most important8.
If biopsies of
various types need testing for HPV, we do IHC at our LML; alternatively, we can send them
to PhenoPath Laboratories in
Seattle, Washington for their preferred method using the Enzo DNA
probe cocktail assays (in 2001, about about a $175 charge direct to patient):
HPV 6, 11, 16, 18, 31, and 33.[S-01-11199].
There are PCR DNA-amplification test methods.
There is an in situ hybridization (ISH) technique (2001) on the
horizon (Kreatech for HPV 1, 2, 6, 11, 16, 18, 31, 33). Now it
is here (2003).
Ventanna has come out (3/2003) with a slide-based
chromogenic in-situ hybridization (CISH) assay (INFORM HPV) that
produces a permanent-record slide for viewing under the microscope: HPV-low 6,
11, 42, 43, 44; HPV-high 16, 18, 31, 33, 35, 45, 51, 52,
56, 58, 59, 68, and 70. Our lab checked this system out between
Nov. '03 and Feb. '04 but did not acquire it. [HPV
testing methods comparison]
- CPT-4 code: 87621 if Digene hi-risk only (one panel); 87621
x2 if both high and low risk panels done.
- ICD-9 codes:
smear topic list & links page
within this website
CAP Today May 2001
Baunoch DA, In Search of a Paradigm, Advance
for Administrators of the Laboratory, page 69, 1 May 2001.
Qureshi MN, et. al. Role of HPV DNA Testing
in Predicting Cervical Intraepithelial Lesions: Comparison
of HC HPV and ISH HPV, Diagnostic Cytopathology 29(3):149-155,
Wright TC, et. al., JAMA 287:2120-2129, 2002.
Volk EE & Wilbur DC, CAP Today, January
Moriarty AT, Q&A of CAP TODAY, July 2004
p. 142 (referring to ASCCP in Arch. Path. & Lab Med 127:959-968,
Wright TC & Cox JT, "Clinical Uses
of Human Papillomavirus (HPV) DNA Testing", a booklet
by ASCCP, 2004 (EBS's office).
- CAP Today November 2007...ASCCP 2006 Consensus Guidelines.
(posted Oct. 2001; latest addition 16 October 2010)