This is controversial! Since this is our pathology group website, the following is obviously the opinion of our decision makers and not the same as an official publication in an official medical or scientific journal. It is our "why so?" to our clients who may be aware that there is controversy in things medical. But, I have decided to replace this "blog-like" page with one that is more retrospective...so this page is being retired to our off-line files as of 5 January 2005.

Since the vast majority of Anatomic Pathology is practiced without FDA attention to details of methods, we are focused on the totality of a process and not to focal FDA approvals or non-approvals (although such FDA positions are noteworthy). To give context, the FDA makes no comment or review of the way a physician takes a medical history or performs a physical exam. Yet, Sir William Osler would still tell the FDA and all others that...except for the patient deciding to present for diagnosis and treatment...there are no more important activities in behalf of patients in all of the field of medicine than a "well performed" H&P! 

Because our group/lab was immediately "under attack" by ThinPrep sales reps & a few clinical physicians in 2000 for not immediately switching to (though we were already committed...had already had the instrument...to the AutoCyte methodology for non-Pap specimens)  ThinPrep when they came marketing to Columbia, S. C., we decided to have a web page to keep our rationale available within our lab & 8-pathologists of our pathology group (and to our clinical physicians and their patients using our services at Lexington Medical Center). We decided to keep, and continue to update, this file as the criticism continues.  Continuing examples: Though our decision was made final some 4 years ago, Cytyc (ThinPrep) won't leave our little niche alone & made contact with some of our clients by passing out "standing order" cards to physician offices for them to mail to labs asking to only be provided with ThinPrep Pap test vials (2/25/04). Chillingly, on 12/27/04, I was FedExed a threatening letter from "Deputy General Counsel" for Cytyc demanding that this webpage  be removed from public (our clients are part of "public") view by 4 January 2005 or risk legal remedies in favor of Cytyc. This letter came without any contact ever from Cytyc, itself,  expressing  concern or making any request to link to a similar but alternative and opposing expression of opinion. So, as of 12/27, I am not totally sure that this letter expresses the true position on the part of Cytyc. It is hard to believe that (in a world of professional societies, published expert literature, and experts ready and willing to give expert advice for decision making) that the opinion of our small, very locally focused practice would be seen as so threatening that they would threaten us with the possibility of unlimited legal action if we did not remove our opinion from view. 

Though we continued to show that our data on a greatly decreased volume of conventional Pap smear cervical cytology is equal to or better than "thin layer" (not really monolayer), liquid-based technology (because, regardless of whether Paps were a money maker, we have always treated them with a full-court press mentality), we have acquiesced to market demand & certainly admit that liquid-based preps have screening advantages. We have offered liquid-based Paps in our lab as of the summer of 2001 (having referred the samples elsewhere beginning in 2000)...we got an "SUV" (liquid based methodology) to supplement our "family vehicle" (conventionals).  

Our internal QA data had shown our conventional work to be excellent, and we were content. ThinPrep marketing came into our area (Spring of 2000) and expertly converted the clinical physician market from contented...to "wanting"...to "needing" liquid-based cervical cytology Paps. Of the two competing brands, we picked the SUV "with 4-wheel drive"...we did not want the "2-wheel drive" brand, regardless of what was or was not published "in the literature" as of early 2000. 

Looking back, we admit that the thin-layer cellular presentation is "cleaner", thereby reducing the "fret factor" in the cytotechnologist's slide screening process.

Four years ago (1997) [check history], and to this date, our due diligence evaluation indicates what we believe to be distinct advantages of SurePath (AutoCyte) (TriPath Imaging...TPTH) over ThinPrep (Cytyc Corp....CYTC). There is no financial advantage, either way, to our pathologists (and we are not in any way beholding to any vendor, by personal ties, provision of "loaner" instruments or equipment, "professional speaker" relationship, or any other factor which would keep us from being strictly objective in our decision in favor of the "4-wheel drive brand"). TriPath is so named because it consists of (1) the SurePath (AutoCyte)  cytology prep system, (2) the acquisition of the old, proven NeoPath computerized screener system, and (3) the acquisition of the old PapNet computerized screener system. The choice of SurePath set us also in position to equip our "vehicle" with "airbags": the FocalPoint supplemental computer screening of all cases (we began this in 9/01).

Caution: sales reps, clinical doctors, and many technologists & pathologists fail to keep their eyes on the precise characteristics of: the (1) clinical strategy for choosing the test method in question (Pap smear...and, for example, never miss an invasive cancer vs. the greatest sensitivity for LGSIL); (2) therefore, the particular "gold standard" for looking at sensitivity, specificity, and predictive values (biopsy vs. PCR, etc.); (3) and therefore, the prevalence of the particular disease of most importance (ca/HGSIL vs. ASCUS/LGSIL). So, choices could vary, depending on the game plan of the cytopathology lab.

Conclusion notes:

1. As to the clinical physician's position:
   • the neutral ACOG position: ACOG, in a 27 July 2001 e-mail to us, confirms that Committee Opinion #206 was withdrawn Dec., 2000, and that not enough data existed/exists for an opinion on conventional vs. thin layer, much less ThinPrep vs. SurePath (AutoCyte). The ACOG update of Dec. 2002 & Opinion of August 2003 remains neutral as to vendor⁸.
   • the Liquid-based advantage of better sensitivity for dysplasia: at least in other labs, many reports indicate (as of early 2001) that liquid-based thin-layer techniques increase the yield of  LGSIL and HGSIL by significant margins over conventional techniques (could this be more a recent result of a combination of [a] the intense marketing discussions and educational focus on the fundamental need for the clinicians to take care to obtain adequate samples; and, [b] the reduction...in the production-quota labs...of the cytotechnologist "fret factor" as they now screen "cleaner" smears?)⁷.
   • Adequacy & reduced "call backs": SurePath (AutoCyte) and our conventional Paps reduce call backs for reasons of "inadequate" or "less than optimal" specimens^2-5...especially as to S-C junction sampling...SurePath having 5 times² less call backs than ThinPrep.
   • Bleeding at office visit: No problem...SurePath (AutoCyte) works the best of the two methods with bloody and/or mucoid specimens...the CytoRich media lyses RBCs and does not "clot" mucous (greatly reduced "call backs" due to obscuring blood due to inadvertent menses at time of Pap); ThinPrep has to go around their FDA-approved process and ask labs to pre-process the specimen to lyse blood. RBC lysis removes the obscuring by the dense red color. But, the mucous and RBC membranes tend to clog the ThinPrep filter; whereas this is not a problem with the SurePath gradient enrichment technology.
   • SurePath (AutoCyte) smear taking is quick: their "Rover Cervex-Broom" single-pass collection device is better and "thumbs off" into the liquid container (ThinPrep, by FDA, must obtain two samples, 1 by brush & 1 by spatula); (but our clinicians correctly point out that the Cervex-Broom cannot be flexed into an anteverted uterine cervix...so, they can use a supplemental endocervix brush & detach the brush end into the fluid); and, 
   • Better SurePath sample integrity: this means 100% of a statistically better cell sample actually goes to the lab (ThinPrep sends less than 100% unless you go outside of their FDA-approved process with time consuming supplemental maneuvers).
   • Superior invasive cancer, cell-clusters, and small-cell detection: SurePath (AutoCyte) better than ThinPrep at detecting cell clusters (postmenopausal endometrials, small cell carcinoma & AGUS) & concern for suboptimal detection of invasive cancer¹ and ThinPrep no better than conventional at detecting invasive cancer⁷...reduced danger to patient and clinician of "failure to diagnose". 
   • ThinPrep's false-negative rate (missing important diagnoses) is twice that of SurePath (AutoCyte) and much higher than our own conventional Paps...SurePath has reduced danger to patient of "failure to diagnose" [a 50,000⁺ case study published late 2001]. By 2002, reports can be interpreted with concern that ThinPrep filter clogs with tumor diathesis debris to the point that may fail to produce diagnosable slide preps of frank cancer^1,7!!!
   • HPV: SurePath (AutoCyte) HPV yield better than ThinPrep yield of HPV positivity on referral testing (ThinPrep brush not FDA approved for HPV sampling) and is just as good as a second patient  encounter specifically just to get an HPV sample.
   • adding "airbags": our lab (contract signed 11 Oct. 2001) also added SurePath (AutoCyte) companion computer screener, AutoPap (FocalPoint) , so that all Pap smears [as of August 2002] are afforded (1) expert cytotechnologist manual screening plus (2) computer-aided screening (as our radiologists are also doing with mammograms via the R2). AutoPap/FocalPoint (prior NeoPath) is the only FDA-approved device for conventional Paps and SurePath (AutoCyte)  Paps (not ThinPrep). In a study (Acta Cytol. 45:704-708, 2001) of 14,777 conventional Paps, AutoPap (FocalPoint)  sorted 100% of abnormal Paps into the quintiles that definitely needed  focused human review (giving a screening "heads up" to the screening cytotechnologist). Cytyc got FDA approval for a competitor computer screener, the ThinPrep Imager System, July 2003.
2. For the lab and hospital:
   • general cost per case payment to "the company" is significantly less with SurePath (AutoCyte). 
   • SurePath (AutoCyte) allows walk-away staining of slides; ThinPrep requires more prep-tech time per case.
   • SurePath (AutoCyte) reagent-rental structure ensures an easy, open-door addition of upgrades (no future "capital budget" hurdles).
   • CytoRich® ethanol-based liquid is non-flammable except at high temperatures  & lyses obscuring blood (ThinPrep's  PreservCyt carries a flammable label & does not lyse blood).
   • ethanol-based cell fixation by SurePath (AutoCyte) is the same fixation as in our conventional technique (makes cells/nuclear structure "look" similar to what we have always been used to in cytopathology).
   • ThinPrep users must go outside of ThinPrep's FDA approved methodology to try to clear obscuring red cells and to present 100% of sample to lab.
   • SurePath (AutoCyte) ethanol-based liquid DOES NOT clot or precipitate mucus and red cell membranes (which, due to their methanol-based liquid, clogs the ThinPrep filters & impairs relative efficacy).
   • SurePath (AutoCyte) robotic aspiration-expression, back & forth syringe manipulation of the collected specimen to disaggregate & homogenize the sample, allows a representative aliquot of sample to be deposited into the centrifuge tube over the density gradient material/jell.  The homogenized cell solution is then pulled through a density gradient using centrifugation to remove obscuring artifacts. A robotic processor then places the jell-filtered cell solution onto a lyseine-coated slide for gravity sedimentation enrichment as the suspended cells settle and attach to the slide surface by way of the "charged" slide surface; this enriched smear prep is better than cloggable suction-filter touch prep method of ThinPrep.
   • much better residual specimen for HPV/STD tests out of the single patient encounter (all of which tests will be managed and offered "in house, on campus" at our hospital as of March 2003).
3. Additional Crucially Important Information:
   • Unfortunately, the THREE vastly more important factors (rather than which technology or brand name) in the effort in behalf of women against uterine cancer are being regularly overlooked in the heat of marketing battles:
     1. a higher percentage of women must be recruited to regular Pap screening.
     2. clinical doctors must do their best to get the best sample from the cervix
     3. labs must employ, compensate, and lead competent cytotechnologists who can screen and find the abnormalities
   • SurePath (AutoCyte) came second (6/1999 for Pap smears) to market (ThinPrep thereby gaining the lead in name-brand recognition) after ThinPrep (5/1996), because:
     1. Cytyc sued TriPath (delaying market entry) for patent infringement.....and lost; and,
     2. the FDA required added studies that they had not required of Cytyc...delaying TriPath until 6/99.
   • ThinPrep 2000-2001 Cytyc sales rep marketing ploy: "Trident Hospital lost all of its Pap business because they got SurePath (AutoCyte)!" A lie...they lost a large account because of  hospital administrative conflict with that clinical practice.
   • ThinPrep 2000-2001 marketing ploy: Orangeburg OB-Gyns want ThinPrep so bad they are sending specimens to LabCorp as of 7/30/01...not true.
   • ThinPrep 2000-2001 marketing ploy: local area LabCorp has both SurePath (AutoCyte) and ThinPrep instruments as of 2001...a lie.
   • Fact: S. C.'s DHEC is poised to use two SurePath (AutoCyte) as soon as budget is approved as of 2001 (as of end of 2003, no liquid based yet).
   • we've been in touch with numerous ThinPrep labs who are going to convert to SurePath (AutoCyte) (as of 2002).
   • Cytyc Corp (ThinPrep) is a publicly traded company with Quest Diagnostics, Inc. being a huge stock owner through an agreement to exclusively use ThinPrep brand of liquid-based Pap technology. TriPath Imaging  is a publicly traded company with major share holders being Roche Laboratories, Inc. and Becton-Dickinson, Inc.
   • One of our excellent OB-Gyns pushing for ThinPrep told us on 1 Aug. 2001, "I haven't had any adequacy problems with my ThinPrep cases. Any that were inadequate or less than optimal had reasons why" [is this "taking a position" on the basis of a small and private study?]. So, we studied (in-house QA) a 250+ case series of his Paps...his "less than optimal due to insufficient endocervical component" rate was 300% higher with ThinPrep than with conventional (7 Aug. 2001)!!!!! Can clinicians remain objective about lab methodologies?
   • We continue to be astounded at the "sore loser" attitude of Cytyc marketing as they hysterically commandeer the valuable time of our busy clinicians, even though our hospital has contracted for, and taken delivery of , the SurePath (AutoCyte)!!! Beyond that, rumor from Cytyc rep has it that the decision was in favor of SurePath (AutoCyte)  because of our hospital Lab vendetta (Oct. 18th, 2001 rumor) against ThinPrep. Re-read this page and show us the evidence against the fact of the decision being strictly as to our assessment of what will be the greatest help and advantage (we aren't vendetta people) to patients.
   • ASCUS rate: With any change to interpretation of liquid-based preps, there is a break-in period during which the lab team will have an increased ASCUS rate. By directorate fiat (you are fired if your ASCUS rate is higher than ___%), we could dictatorially reduce that rate (but don't direct our lab in that manner). Though being highly sensitive to clinician chart backlog caused by ASCUS cases, we must keep our prime focus on avoiding any "failure to diagnose" important lesions. We continue to press to reduce the ASCUS rate.

References:

1. Clark SB, et. al., Invasive Squamous Cell Carcinoma in ThinPrep Specimens: Diagnostic Clues in the Cellular Pattern, Diagnostic Cytopathology, 26:1-4, 2002 (Cleveland Clinic...study of 13 SCC cases).

2. Nance KV, SurePath vs. ThinPrep in a Low Prevalence Population, Acta Cytologica 46:953, 2002.

3. Nance KV,  Conversion from ThinPrep to SurePath: How to Validate, Acta Cytologica 46:952, 2002.

4. Bolick DR, Comparison of the Detection Rate of Pap Abnormalities in Autocyte Prep and ThinPrep Pap Test Specimens, Acta Cytologica 45:831-832, 2001.

5. Fite SK, Impact of Converting ThinPrep to SurePath on Overall Sensitivity and Adequacy, Acta Cytologica 46:958, 2002.

6. Nance KV, their lab's (Rex Health Care, Raleigh, NC) Nov. 2002 newsletter, at the American Society of Cytology annual meeting, 2002, Salt Lake City, Utah.

7. Limaye A, et. al., Comparative Analysis of Conventional Pap. Tests and a Fluid-based Thin-layer Method, Archives of Path. and Lab. Medicine, Feb. 2003. (1.4 million cases, Quest Labs, Teteroro, N. J.)

8. ACOG, Technology Assessment in Obstetrics and Gynecology: Cervical Cytology Screening, #2, Dec. 2002.

9. Bolick DR, Comparison of the False Negative Fraction in Autocyte Preps, ThinPrep Pap Tests, and Conventional Pap Smears,

[posted 19 July 2001; latest addition 5 January 2005]