Cytological specimen (ThinPrep) from a patient who was later diagnosed with cervical adenocarcinoma in situ. Cervical cancer is Malignant Cancer of the Cervix uteri or cervical area There is at least one mitosis. Mitosis is the process in which a Eukaryotic cell separates the Chromosomes in its Cell nucleus, into two identical sets in two daughter nuclei

In gynecology, the Papanikolaou test or Papanicolaou test (also called Pap smear, Pap test, cervical smear, or smear test) is a medical screening method, invented independently by Aurel Babeş^[1] and Georgios Papanikolaou, primarily designed to detect premalignant and malignant processes in the ectocervix. Gynaecology or gynecology (see spelling differences) refers to the surgical specialty dealing with health of the female reproductive system ( Uterus Aurel Babeş was a Romanian scientist and one of the discoverers of the vaginal smear as screening test for Cervical cancer. Georgios N Papanikolaou (or George Papanicolaou; Γεώργιος Παπανικολάου) ( May 13, 1883 &ndash February 19, The cervix (from Latin "neck" is the lower narrow portion of the Uterus where it joins with the top end of the Vagina. It may also detect infections and abnormalities in the endocervix and endometrium.

The endocervix may be partially sampled with the device used to obtain the ectocervical sample, but due to the anatomy of this area, consistent and reliable sampling cannot be guaranteed. As abnormal endocervical cells may be sampled, those examining them are taught to recognize them.

The endometrium is not directly sampled with the device used to sample the ectocervix. Cells may exfoliate onto the cervix and be collected from there, so as with endocervical cells, abnormal cells can be recognised if present but the Pap Test should not be used as a screening tool for endometrial malignancy.

The potentially pre-cancerous changes (called dysplasias or cervical or endocervical intraepithelial neoplasia) are usually caused by sexually transmitted human papillomaviruses (HPVs). Dysplasia (from Greek roughly "bad formation" is a term used in Pathology to refer to an abnormality in maturation of cells within a tissue A human papillomavirus ( HPV) is a Papillomavirus that infects the skin and Mucous membranes of Humans Approximately 130 HPV types have been The test aims to detect and prevent the progression of HPV-induced cervical cancer and other abnormalities in the female genital tract by sampling cells from the outer opening of the cervix (Latin for "neck") of the uterus and the endocervix. Cervical cancer is Malignant Cancer of the Cervix uteri or cervical area A sex organ, or primary sexual characteristic, as narrowly defined is any of the anatomical parts of the body which are involved in sexual reproduction and constitute The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called The cervix (from Latin "neck" is the lower narrow portion of the Uterus where it joins with the top end of the Vagina. The uterus (from the Latin word for womb) is the major Female reproductive organ of most Mammals including Humans One end the The sampling technique changed very little since its invention by Georgios Papanikolaou (1883–1962) to detect cyclic hormonal changes in vaginal cells in the early 20th century until the development of liquid based cell thinlayer technology. Georgios N Papanikolaou (or George Papanicolaou; Γεώργιος Παπανικολάου) ( May 13, 1883 &ndash February 19, The test remains an effective, widely used method for early detection of cervical cancer and pre-cancer.

The UK's call and recall system is among the best; estimates of its effectiveness vary widely but it may prevent about 700 deaths per year in the UK.

It is not a perfect test. "A nurse performing 200 tests each year would prevent a death once in 38 years. During this time she or he would care for over 152 women with abnormal results, over 79 women would be referred for investigation, over 53 would have abnormal biopsy results, and over 17 would have persisting abnormalities for more than two years. At least one woman during the 38 years would die from cervical cancer despite being screened. "^[2] HPV vaccine may offer better prospects in the long term. Human papillomavirus (HPV vaccine is a Vaccine that targets certain strains of Human papillomavirus associated with the development of Cervical

It is generally recommended that females who have had sex seek regular Pap smear testing. Guidelines on frequency vary, from annually to every five years. If results are abnormal, and depending on the nature of the abnormality, the test may need to be repeated in three to twelve months. If the abnormality requires closer scrutiny, the patient may be referred for detailed inspection of the cervix by colposcopy. Colposcopy is a medical diagnostic procedure to examine an illuminated magnified view of the Cervix and the tissues of the Vagina and Vulva. The patient may also be referred for HPV DNA testing, which can serve as an adjunct to Pap testing. A human papillomavirus ( HPV) is a Papillomavirus that infects the skin and Mucous membranes of Humans Approximately 130 HPV types have been

About 5% to 7% of pap smears produce abnormal results, such as dysplasia, possibly indicating a pre-cancerous condition. Dysplasia (from Greek roughly "bad formation" is a term used in Pathology to refer to an abnormality in maturation of cells within a tissue Although many low grade cervical dysplasias spontaneously regress without ever leading to cervical cancer, dysplasia can serve as an indication that increased vigilance is needed. Cervical cancer is Malignant Cancer of the Cervix uteri or cervical area Endocervical and endometrial abnormalities can also be detected, as can a number of infectious processes, including yeast and Trichomonas vaginalis. A small proportion of abnormalities are reported as of "uncertain significance".

Technical aspects

Samples are collected from the outer opening or os of the cervix using an Aylesbury spatula and an endocervical brush, or (more frequently with the advent of liquid-based cytology) a plastic-fronded broom. The broom is not as good a collection device, since it is much less effective at collecting endocervical material as the spatula and brush. ^[3] The cells are placed on a glass slide and checked for abnormalities in the laboratory. A laboratory (informally lab) is a facility that provides controlled conditions in which scientific Research, Experiments and

The sample is stained using the Papanicolaou technique, in which tinctorial dyes and acids are selectively retained by cells. In Medicine, a tincture is an Alcoholic Extract (eg of leaves or other plant material or Solution of a non- volatile substance Unstained cells cannot be visualized with light microscopy. The stains chosen by Papanicolau were selected to highlight cytoplasmic keratinization, which actually has almost nothing to do with the nuclear features used to make diagnoses now.

The sample is then screened by a specially trained and qualified cytotechnologist using a light microscope. A microscope ( Greek: ( micron) = small + ( skopein) = to look or see is an instrument for viewing objects that are The terminology for who screens the sample varies according the country; in the UK, the personnel are known as Cytoscreeners, Biomedical scientists (BMS), Advanced Practitioners and Pathologists. The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located A biomedical scientist (or biomedical doctor, biomedician, medical scientist) is a scientist educated in the field of Biological science, especially Pathology (from Greek grc πάθος pathos, "fate harm" and grc -λογία -logia) is the study and The latter two take responsibility for reporting the abnormal sample which may require further investigation.

Studies of the accuracy of conventional cytology report:^[4]

• sensitivity 72%
• specificity 94%

In the United States, physicians who fail to diagnose cervical cancer from a pap smear have been convicted of negligent homicide. The United States of America —commonly referred to as the A physician, medical practitioner or medical doctor who practices Medicine, and is concerned with maintaining or restoring human Health Diagnosis is the identification by Process of elimination, of the nature of anything Negligent homicide is a charge brought against people who by inaction allow others under their care or presence intentionally to die In 1988 and 1989, Karen Smith had received pap smears which were argued to have "unequivocally" shown that she had cancer; yet the lab had not made the diagnosis. Year 1988 ( MCMLXXXVIII) was a Leap year starting on Friday (link displays 1988 Gregorian calendar) Year 1989 ( MCMLXXXIX) was a Common year starting on Sunday (link displays 1989 Gregorian calendar) She died on March 8, 1995. Events 1618 - Johannes Kepler discovers the third law of planetary motion. Year 1995 ( MCMXCV) was a Common year starting on Sunday. Events of 1995 Later, a physician and a laboratory technician were convicted of negligent homicide. These events have led to even more rigorous quality assurance programs, and to emphasizing that this is a screening, not a diagnostic, test, associated with a small irreducible error rate.

Liquid based monolayer cytology

Since the mid-1990s, techniques based around placing the sample into a vial containing a liquid medium which preserves the cells have been increasingly used. The media are primarily ethanol based. Two of the types are Sure-Path (TriPath Imaging) and Thin-Prep (Cytyc Corp). 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 low and high risk HPV testing and reduced unsatisfactory specimens from 4. 1% to 2. 6%. ^[5] Proper sample acquisition is crucial to the accuracy of the test; clearly, a cell that is not in the sample cannot be evaluated.

Studies of the accuracy of liquid based monolayer cytology report:

• sensitivity 61%^[6] to 66%^[4]
• specificity 82%^[6] to 91%^[4]

Some^[5], but not all studies^[4][6], report increased sensitivity from the liquid based smears.

Human papillomavirus testing

The presence of HPV indicates that the person has been infected, the majority of women who get infected will successfully clear the infection within 18 months. A human papillomavirus ( HPV) is a Papillomavirus that infects the skin and Mucous membranes of Humans Approximately 130 HPV types have been It is those who have an infection of prolonged duration with high risk types^[7] (e. g. types 16,18,31,45) that are more likely to develop Cervical Intraepithelial Neoplasia due to the effects that HPV has on DNA. Studies of the accuracy of HPV testing report:

• sensitivity 88% to 91% (for detecting CIN 3 or higher)^[6] to 97% (for detecting CIN2+)^[8]
• specificity 73% to 79% (for detecting CIN 3 or higher)^[6] to 93% (for detecting CIN 3 or higher)^[8]

By adding the more sensitive HPV Test, the specificity may decline. A human papillomavirus ( HPV) is a Papillomavirus that infects the skin and Mucous membranes of Humans Approximately 130 HPV types have been However, the drop in specificity is not definite. ^[9] If the specificity does decline, this results in increased numbers of false positive tests and many women who did not have disease having colposcopy^[10] and treatment. A worthwhile screening test requires a balance between the sensitivity and specificity to ensure that those having a disease are correctly identified as having it and equally importantly those not identifying those without the disease as having it. Screening, in medicine is a strategy used in a Population to detect a Disease in individuals without signs or Symptoms of that disease Due to the liquid based pap smears having a false negative rate of 15-35%, the American College of Obstetricians and Gynecologists and American Society for Colposcopy and Cervical Pathology^[11] have recommended the use of HPV testing in addition to the pap smear in all women over the age of 30. The American College of Obstetricians and Gynecologists ( ACOG) is a Professional association of Medical doctors specializing in Obstetrics and A human papillomavirus ( HPV) is a Papillomavirus that infects the skin and Mucous membranes of Humans Approximately 130 HPV types have been

Regarding the role of HPV testing, randomized controlled trials have compared HPV to colposcopy. A human papillomavirus ( HPV) is a Papillomavirus that infects the skin and Mucous membranes of Humans Approximately 130 HPV types have been A randomized controlled trial (RCT is a type of scientific Experiment most commonly used in testing the Efficacy or Effectiveness of Healthcare A human papillomavirus ( HPV) is a Papillomavirus that infects the skin and Mucous membranes of Humans Approximately 130 HPV types have been Colposcopy is a medical diagnostic procedure to examine an illuminated magnified view of the Cervix and the tissues of the Vagina and Vulva. HPV testing appears as sensitive as immediate colposcopy while reducing the number of colposcopies needed. A human papillomavirus ( HPV) is a Papillomavirus that infects the skin and Mucous membranes of Humans Approximately 130 HPV types have been Colposcopy is a medical diagnostic procedure to examine an illuminated magnified view of the Cervix and the tissues of the Vagina and Vulva. ^[12] Randomized controlled trial have suggested that HPV testing could follow abnormal cytology^[6] or could precede cervical cytology examination. A randomized controlled trial (RCT is a type of scientific Experiment most commonly used in testing the Efficacy or Effectiveness of Healthcare A human papillomavirus ( HPV) is a Papillomavirus that infects the skin and Mucous membranes of Humans Approximately 130 HPV types have been ^[8]

A study published in April 2007 suggested the act of performing a Pap smear produces an inflammatory cytokine response, which may initiate immunologic clearance of HPV, therefore reducing the risk of cervical cancer. Cytokines are a category of signalling Proteins and Glycoproteins that like Hormones and Neurotransmitters, are used extensively in cellular Women who had even a single Pap smear in their history had a lower incidence of cancer. "A statistically significant decline in the HPV positivity rate correlated with the lifetime number of Pap smears received. "^[13]

Automated analysis

In the last decade there have been successful attempts to develop automated, computer image analysis systems for screening. ^[14] Automation may improve sensitivity and reduce unsatisfactory specimens. ^[15] One of these has been FDA approved and functions in high volume reference laboratories, with human oversight.

Practical aspects

The physician or operator collecting a sample for the test inserts a speculum into the patient's vagina, to obtain a cell sample from the cervix. speculum is a medical tool for investigating body cavities with a form dependent on the body cavity for which it is designed The cervix (from Latin "neck" is the lower narrow portion of the Uterus where it joins with the top end of the Vagina. A pap smear appointment is normally not scheduled during menstruation. The procedure is usually painful, because of the neuroanatomy of the cervix. However, this can depend on the patient's anatomy, the skill of the practitioner, psychological factors, and other conditions. Anatomy (from the Greek anatomia, from ana separate apart from and temnein, to cut up cut open is a branch of Biology that is the consideration Results usually take about 3 weeks. Slight bleeding, cramps, and other discomfort can occur afterwards.

Other tests, including the TruTest, an endometrial biopsy used for early detection of uterine cancer, can be performed during the same visit. A biopsy is a medical procedure used to remove a sample of tissue from the patient to be analyzed and diagnosed by a physician The term uterine cancer may refer to any of several different types of Cancer which occur in the Uterus, namely Uterine sarcomas

References

External links

• Jo's Trust - UK's leading cervical cancer charity.
• Imaginis - Pap Smear information
• International Agency for Research on Cancer - Resource about screening, including that of Cervical Cancer. There are digital atlases of coloscopy, histology and cytology, the rationale of screening and setting up of a screening programme.
• The Pap Test: Questions and Answers — National Cancer Institute — from the U. S. 's National Cancer Institute
• Pap Smear — from eMedicineHealth
• MedlinePlus: Cervical Cancer Prevention/Screening — from MedlinePlus
• The Bethesda 2001 Workshop, held April 30 - May 2, 2001, reviewed issues regarding terminology and reporting of cervical cytology
• NCI Bethesda System Web Atlas, with 349 images of different Pap smear morphologic findings — from the American Society of Cytopathology
• Canadian Guidelines for Cervical Cancer Screening - Society of Obstetricians and Gynaecologists of Canada
• The UK's National Association of Cytologists
• British Society for Clinical Cytology
• IBMS — The Institute of Biomedical Science on cellular pathology
• NHS Cervical Screening Programme — from the UK's National Health Service
• EngenderHealth- Cervical Cancer Screening
• Video of taking a smear using a wooden tool - from University of Florida, Department of Obstetrics and Gynecology
• Video of taking a smear using a brush - from University of Florida, Department of Obstetrics and Gynecology