Liquid-based Pap tests and Conventional Pap Smear

Studies have shown that Liquid Based Pap Tests increase detection of precancerous cells over the conventional smear based glass slide Pap smear.

The Liquid Based Pap Test is the most widely used method for cervical cancer screening in the United States. It was developed to address the limitations of the conventional Pap smear, and after rigorous clinical trials, it was approved by the U.S. Food and Drug Administration (FDA) as a replacement for the conventional Pap smear. The Liquid Based Pap Test is a cytology method approved by the FDA found to be "significantly more effective" than the conventional Pap smear for detection of cervical abnormalities.

Most importantly, since FDA approval, more than 170 studies have been published, in peer-reviewed medical journals, demonstrating a wide range of clinical benefits of the Liquid Based Pap Test including increased disease detection, reduction of equivocal diagnoses, improved specimen adequacy and the ability to perform additional tests out of the same vial. Liquid based Pap Tests , after proper validation, are currently approved by the FDA for a variety of out of the vial tests, including HPV, CT, NG, and HSV as well as any potential agent that is DNA based and can be identified using sophisticated DNA testing.

To date there have been more than 30 studies published in peer-reviewed journals, reporting on nearly 400,000 patients that show a significant increase in the detection of both low grade and high grade lesions using the Liquid based Pap Tests compared to the conventional Pap smear.

Liquid Based Process ThinPrep® Process
1. Dispersion: Randomizes/homogenizes patient population within the vial.
2. Cell Collection: software monitors the flow rate and senses when pores are blocked by material (red blood cells [RBCs], white blood cells [WBCs], and epithelial cells).
3. Cell Transfer: Cylinder is inverted and filter comes in contact with glass slide. Air pressure from behind the filter aids the cell's natural attraction to the glass slides.

Clinical Studies

Meta-analysis of 25 articles published between 1990-2000 comparing diagnostic cytology and specimen adequacy of the two tests for 67,484 patients.

Odds ratios favored the Liquid Based Pap Tests over the conventional Pap smear in regard to the diagnosis of LSIL and HSIL; adequacy was improved in the Liquid Based Pap Test group in all trials.

* Bernstein SJ, Sanchez-Ramos L, Ndubisi B. Liquid-based cervical cytologic smear study and conventional Papanicolaou smears: A metaanalysis of prospective studies comparing cytologic diagnosis and sample adequacy. Am J Obstet Gynecol. 2001;185:308-317.

Conventional Pap Smear

Conventional Pap Slide

Microscopically, the uneven distribution of cellular material associated with the Conventional Pap Smear pattern is evident.

Liquid Based Pap Test

Liquid Based Pap Slide
This slide is the from the same patient as the slide above. Tissue architecture is maintained. Liquid based technology rearranges the relationship of cell groups on the glass slide. A group/sheet of endocervical cells present represents this.

ThinPrep® Characteristics

Common changes associated with ThinPrep® morphology

  • Key difference is the wet fixation
  • Cell size, related to the cells placed into solution
  • Smear Pattern, no longer smearing cellular material across the glass slide
  • Specimen Background, unique characteristics

Wet Fixation

  • Enhanced cytoplasmic detail
  • Enhanced nuclear detail. Optimized fixation, no longer smearing the cells onto a dry glass slide. Sample rinsed directly into a fluid solution.
  • Wet fixation allows for more variability in nuclear staining. The chromatin detail is more readily appreciated and can appear as hypo- and hyperchromatic nuclei with the same case.

Cell Size

  • "Proportionally" smaller cells: inherent difference with alcohol fixation eliminated air-drying artifact.
  • Single cells are more prominent: Single cell populations are not created, just more noticeable in the background.
  • Cells round up in solution: physical properties, similar to non-gyn presentation.

Smear Pattern

  • Mechanical artifacts associated with pulling the cells across the slide have been eliminated
  • Cellular material is not pulled out in mucus - chance to establish new pattern recognition for ThinPrep®. Endocervical cells will be distributed throughout cell deposit and not caught up in mucus.
  • Tissue architecture is maintained throughout the slide processing. Architecture is not destroyed, only the relationships of the cell groupings have been altered.

Specimen Background

  • Specimen background is cleaner as a result of the filtration process. Microscopically you will see more light passing through the slide.
  • Fluid collection causes the cellular debris to clump
  • Background provides clues. Initially, ThinPrep® takes more vigilance when screening. More information per field. Information is typically obscured on the Conventional Pap Smear but is more easily identified in the background on a ThinPrep® slide.
  • "Ratty" background can be advantageous during diagnosis: infectious agents, cytolysis, disease should be considered. Tumor diathesis, blood, cytolysis will be still be present on the slide and should be used in the differential diagnosis.

Historic Validation of the ThinPrep® Pap Test

  • Over 15,000,000 samples processed
  • Over 282,000 specimens evaluated in peer-review studies
  • Over 16,500 US physicians rinsing
  • Over 700 US laboratories processing
  • Over 200 US health plans cover the ThinPrep Pap Test

Improved sensitivity in clinical trail: 65% increase in screening population, and 6% increase in high-risk population.

Improved specimen adequacy with routine use: 35% reduction in "Satisfactory by limited by" specimens and 73% reduction in "Unsatisfactory" specimens.

Human papilloma viruses (HPV) are clinically regarded as the most important pathogens of the human anogenital tract and the main factor in the development of cervical and anal cancer. HPVs are a diverse group of DNA viruses involved in human disease, with more than 100 different types identified. The identification and typing of HPVs (Human Papilloma Viruses) has become increasingly challenging, due to the numerous viral types that must be detected and their role in the process of cervical neoplasia. A Pap test only indicates the possibility of infection with HPV and the possibility of changes associated with cervical cancer. For a more direct diagnosis, a molecular diagnostic system for HPV typing accurately detects different HPV subtypes, some of which are particularly aggressive and directly associated with high grade dysplasia and malignancy. Precancerous changes are found in all age groups but are particularly frequent in younger women. These changes as well as cervical cancer are some of the most successfully treated cancers when detected early.

Type-specific identification of HPV DNA and the genotyping of the virus is important for disease prevention, prognosis, and treatment. Until now, an efficient method for HPV typing was not available. HPV types are categorized as “high risk” or “low risk” based on their relative risks of oncogenesis. There are over 45 different types of HPV that cause genital infections. Co-infections by multiple HPV types are likely to occur in more than 30% of HPV patients. Certain combinations of these co-infections may be more prone to cause cancer than others. Information regarding HPV co-infections can be an essential part of determining treatment options and immunotherapy. Our molecular diagnostic system identifies over 40 HPV types, especially those associated with high grade dysplasia (HSIL) and provides the necessary information for managing disease and improving patient care.

Guidelines for Women Age 30 and Older

A February 2004 article in Obstetrics & Gynecology was published detailing the consensus reached on management guidelines for women age 30 and older based on results from a combination of cervical cytology with High-Risk HPV DNA testing, modified by West Coast Pathology Laboratories

Cytology negative
HPV negative
Cytology negative
HPV positive
Cytology ASC-US
HPV negative
Cytology ASC-US
HPV positive
and HPV result
Routine Screening
at Routine Interval
Repeat both tests at
12 months or
Repeat cytology at
12 months or
Colposcopy Colposcopy
Both negative Cytology ASC-US
HPV negative
HPV negative
Cytology ASC-US
HPV positive
Routine Screening
at 3 years or sooner
Rescreen with Cytology
and HPV at 12 months
or sooner
Colposcopy Colposcopy

 Cytology negative and High-Risk HPV DNA negative: Take into consideration health and risk factors. Screen at routine interval.

 Cytology negative and High-Risk HPV DNA positive: Repeat both cytology and High-Risk HPV DNA test 12 months or sooner. If repeated test results are negative, rescreening at routine interval. If either repeated result is positive, a colposcopy should be performed for a more careful evaluation. If colposcopy is normal, rescreening with both tests should be performed at 12 months or sooner.

 ASC-US result and High-Risk HPV DNA negativeA cytology test should be repeated in 12 months or sooner.

 ASC-US result and High-Risk HPV DNA positive: A colposcopy should be performed for a more careful evaluation.

 Cytology results ASC-HLSIL or HSIL and High-Risk HPV DNA negative or positive: A colposcopy should be performed for more careful evaluation

The combined test results should be used in conjunction with other clinical information when making patient management decisions.