cervical cytology

Cervical screening is a way of preventing cervical cancer from developing, and diagnosing the disease at an early pre-cancerous stage.

In the USA, cervical screening is usually performed using the "Pap test" (or ’smear test’), though the UK screening programmes changed the screening method to "liquid-based cervical cytology" in 2008.

Screening tests look for pre-cancerous changes in the cervix that could develop into cervical cancer.

Conventional cytology ("Pap test" or "Pap smear")

In the conventional Pap smear, the physician collecting the cells smears them on a microscope slide and applies a fixative. In general, the slide is sent to a laboratory for evaluation.

Studies of the accuracy of conventional cytology report:
 sensitivity: 72%
 specificity: 94%

Liquid-based monolayer cytology

Since the mid-1990s, techniques based on placing the sample into a vial containing a liquid medium that preserves the cells have been increasingly used.

Two of the types are Sure-Path (TriPath Imaging) and Thin-Prep (Cytyc Corp). The media are primarily ethanol-based for Sure-Path and methanol for ThinPrep. Once placed into the vial, the sample is processed at the laboratory into a cell thin-layer, stained, and examined by light microscopy.

The liquid sample has the advantage of being suitable for high-risk HPV testing and may reduce unsatisfactory specimens from 4.1% to 2.6%.

Proper sample acquisition is crucial to the accuracy of the test, as a cell that is not in the sample cannot be evaluated.

Studies of the accuracy of liquid based monolayer cytology report:
 sensitivity: 61% to 66%
 specificity: 82% to 91%

HPV testing and HPV typing

Human papillomavirus (HPV) infection is a cause of nearly all cases of cervical cancer. Most women will successfully clear HPV infections within 18 months. Those that have a prolonged infection with a high-risk (e.g. types HPV-16, HPV-18, HPV-31, HPV-45) are more likely to develop Cervical Intraepithelial Neoplasia (CIN).

Studies of the accuracy of HPV testing report:
 sensitivity: 88% to 91% (for detecting CIN 3 or higher) to 97% (for detecting CIN2+)
 specificity: 73% to 79% (for detecting CIN 3 or higher) to 93% (for detecting CIN2+)

Regarding the role of HPV testing, randomized controlled trials have compared HPV to colposcopy.

HPV testing appears as sensitive as immediate colposcopy while reducing the number of colposcopies needed.

Randomized controlled trial have suggested that HPV testing could follow abnormal cytology or could precede cervical cytology examination.

HPV testing can reduce the incidence of grade 2 or 3 cervical intraepithelial neoplasia or cervical cancer detected by subsequent screening tests among women 32–38 years old according to a randomized controlled trial. The relative risk reduction was 41.3%. For patients at similar risk to those in this study (63.0% had CIN 2-3 or cancer), this leads to an absolute risk reduction of 26%. 3.8 patients must be treated for one to benefit (number needed to treat = 3.8).

Reporting: The Bethesda system

In the US and in many other countries, cytology is reported according to the Bethesda System.

HSIL or LSIL cytology is the usual trigger to initiate colposcopy and/or diagnostic conization.

The presence of atypical squamous cells of undetermined significance (ASCUS) or atypical glandular cells of undetermined significance (AGUS) cytology, in particular when associated with high-risk human papillomavirus (HPV) and no colposcopic anomaly, also may require the same approach.

Cytologic categories must be distinguished carefully from histologic diagnoses.

Cytology has a high sensitivity for CIN, in general, but a low specificity for its grade. Regrettably, cytologic and histologic diagnostic terms often are used interchangeably. Cytology tends to underestimate the severity of CIN.

As an example, high-grade (grades 2 and 3) CIN was preceded by HSIL in only 31% of cases in data compiled from 6 publications.