Cervical screening
Encyclopedia
Cervical screening is a way of preventing cervical cancer
from developing, and diagnosing the disease at an early 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 cytology in 2008.
Screening tests look for pre-cancerous changes in the cervix
that could develop into cervical cancer. If the abnormal tissue or cells can be removed, then the disease can be prevented from developing and causing problems. The tests can also diagnose the disease by identifying cancer cells that are already present.
Studies of the accuracy of conventional cytology report:
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:
(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 type (e.g. types 16, 18, 31, 45) 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:
By adding the more sensitive HPV Test, the specificity may decline. However, the drop in specificity is not definite. If the specificity does decline, the result is increased numbers of false positive tests and, for many women that did not have disease, an increased risk for colposcopy 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 those without the disease are not identified as having it.
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.
A study published in April 2007 suggested that 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. Women that 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."
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). Click here to adjust these results for patients at higher or lower risk of CIN 2-3.
With HPV testing, there was a 50 percent reduction in the number of deaths from cervical cancer compared to unscreened women. Compared to other methods, the research showed the HPV testing reported the fewest false negatives.
Visual inspection of the cervix, using acetic acid (white vinegar; VIA) or Lugol’s iodine (VILI) to highlight precancerous lesions so they can be viewed with the "naked eye", shifts the identification of precancer from the laboratory to the clinic. Such procedures eliminate the need for laboratories and transport of specimens, require very little equipment and provide women with immediate test results. A range of medical professionals—doctors, nurses, or professional midwives—can effectively perform the procedure, provided they receive adequate training and supervision. As a screening test, VIA may perform as well as or better than cervical cytology in accurately identifying pre-cancerous lesions. This has been demonstrated in various studies where trained physicians and mid-level providers correctly identified between 45% and 79% of women at high risk of developing cervical cancer. By comparison, the sensitivity of cytology has been shown to be between 47 and 62%. Cytology provides higher specificity (fewer false positives) than VIA. Like cytology, one of the limitations of VIA is that results are highly dependent on the accuracy of an individual's interpretation. This means that initial training and on-going quality control are of paramount importance. Increased false positives are particularly important in a screen-and-treat setting, since over-treatment and resulting impairment of fertility is more likely.
VIA can offer significant advantages over Pap in low-resource settings, particularly in terms of increased screening coverage, improved follow-up care and overall program quality. Due to the need for fewer specialized personnel and less infrastructure, training, and equipment, with VIA public health systems can offer cervical cancer screening in more remote (and less equipped) health care settings and can achieve higher coverage. Furthermore, providers can share the results of VIA with patients immediately, making it possible to screen and treat women during the same visit. This helps ensure that follow-up care can be provided on the spot and reduces the number of women who may miss out on treatment because they are not able to return to the clinic at another time. In a "screen and treat" project in Peru, for example, only 9% of women who screened positive failed to receive treatment in the single-visit approach, compared with 44% of women who were lost to treatment using a multi-visit model.
VIA has successfully been paired with cryotherapy, a relatively simple and inexpensive method of treating cervical lesions that can be performed by primary care physicians and mid-level providers.
To take the sample of cells, the doctor or nurse puts an instrument called a speculum inside the vagina. The speculum has two arms that spread the sides of the vagina apart so that the doctor or nurse can see the cervix. Then they scrape the surface of the cervix with a spatula or small brush. This collects a sample of cells from the outer layer of the cervix.
With a Pap smear, cells collected using a spatula are smeared onto a slide for examination under a microscope. In liquid-based cytology, a sample of cells is taken using a small brush. The cells are put it into a pot of liquid, and analysed for abnormalities. Cervical cells to be tested for HPV
are collected in a similar way.
), or CIS (carcinoma in situ
) - these terms describe different levels of abnormality found in the cervical cells. Abnormal cells can be removed or destroyed using one of several different procedures.
Laser ablation and cryotherapy
treat just the part of the cervix that contains abnormal cells. Laser ablation uses a laser to burn away the abnormal cells, while cryotherapy uses a cold probe to freeze the cells away. These procedures allow normal cells to grow back in their place. The loop electrical excision procedure
(called LLETZ or 'large loop excision of the transformation zone' in the UK), cervical conization
(or cone biopsy) and hysterectomy
remove the whole area containing the cells that could become pre-cancerous or develop into cervical cancer.
Cervical cancer
Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. One of the most common symptoms is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer is in its advanced stages...
from developing, and diagnosing the disease at an early 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 cytology in 2008.
Screening tests look for pre-cancerous changes in the cervix
Cervix
The cervix is the lower, narrow portion of the uterus where it joins with the top end of the vagina. It is cylindrical or conical in shape and protrudes through the upper anterior vaginal wall...
that could develop into cervical cancer. If the abnormal tissue or cells can be removed, then the disease can be prevented from developing and causing problems. The tests can also diagnose the disease by identifying cancer cells that are already present.
Conventional cytology
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 (CytycCytyc
Cytyc Corporation was a company engaged in the design, development, manufacture, and marketing of clinical products that focus on women’s health. Its products covered a range of women's health applications, including cervical cancer screening, breast cancer risk assessment, treatment of excessive...
Corp). The media are primarily ethanol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
-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%, (although some studies report increased sensitivity from liquid-based smears)
- specificity 82% to 91%
Human papillomavirus testing
Human papillomavirusHuman papillomavirus
Human papillomavirus is a member of the papillomavirus family of viruses that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes...
(HPV) infection is a cause of nearly all cases of cervical cancer
Cervical cancer
Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. One of the most common symptoms is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer is in its advanced stages...
. Most women will successfully clear HPV infections within 18 months. Those that have a prolonged infection with a high-risk type (e.g. types 16, 18, 31, 45) are more likely to develop Cervical Intraepithelial Neoplasia
Cervical intraepithelial neoplasia
Cervical intraepithelial neoplasia , also known as cervical dysplasia and cervical interstitial neoplasia, is the potentially premalignant transformation and abnormal growth of squamous cells on the surface of the cervix. CIN is not cancer, and is usually curable...
, due to the effects that HPV has on DNA.
Studies of the accuracy of HPV
Human papillomavirus
Human papillomavirus is a member of the papillomavirus family of viruses that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes...
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+)
By adding the more sensitive HPV Test, the specificity may decline. However, the drop in specificity is not definite. If the specificity does decline, the result is increased numbers of false positive tests and, for many women that did not have disease, an increased risk for colposcopy and treatment. A worthwhile screening
Screening (medicine)
Screening, in medicine, is a strategy used in a population to detect a disease in individuals without signs or symptoms of that disease. Unlike what generally happens in medicine, screening tests are performed on persons without any clinical sign of disease....
test requires a balance between the sensitivity and specificity to ensure that those having a disease are correctly identified as having it and those without the disease are not identified as having it.
Regarding the role of HPV
Human papillomavirus
Human papillomavirus is a member of the papillomavirus family of viruses that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes...
testing, randomized controlled trials have compared HPV
Human papillomavirus
Human papillomavirus is a member of the papillomavirus family of viruses that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes...
to colposcopy
Colposcopy
Colposcopy is a medical diagnostic procedure to examine an illuminated, magnified view of the cervix and the tissues of the vagina and vulva. Many premalignant lesions and malignant lesions in these areas have discernible characteristics which can be detected through the examination...
. HPV
Human papillomavirus
Human papillomavirus is a member of the papillomavirus family of viruses that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes...
testing appears as sensitive as immediate colposcopy
Colposcopy
Colposcopy is a medical diagnostic procedure to examine an illuminated, magnified view of the cervix and the tissues of the vagina and vulva. Many premalignant lesions and malignant lesions in these areas have discernible characteristics which can be detected through the examination...
while reducing the number of colposcopies needed. Randomized controlled trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
have suggested that HPV
Human papillomavirus
Human papillomavirus is a member of the papillomavirus family of viruses that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes...
testing could follow abnormal cytology or could precede cervical cytology examination.
A study published in April 2007 suggested that the act of performing a Pap smear produces an inflammatory cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
response, which may initiate immunologic clearance of HPV, therefore reducing the risk of cervical cancer. Women that 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."
HPV testing can reduce the incidence of grade 2 or 3 cervical intraepithelial neoplasia
Cervical intraepithelial neoplasia
Cervical intraepithelial neoplasia , also known as cervical dysplasia and cervical interstitial neoplasia, is the potentially premalignant transformation and abnormal growth of squamous cells on the surface of the cervix. CIN is not cancer, and is usually curable...
or cervical cancer detected by subsequent screening tests among women 32–38 years old according to a randomized controlled trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
. The relative risk reduction
Relative risk reduction
In epidemiology, the relative risk reduction is a measure calculated by dividing the absolute risk reduction by the control event rate.The relative risk reduction can be more useful than the absolute risk reduction in determining an appropriate treatment plan, because it accounts not only for the...
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
Absolute risk reduction
In epidemiology, the absolute risk reduction or risk difference is the decrease in risk of a given activity or treatment in relation to a control activity or treatment. It is the inverse of the number needed to treat....
of 26%. 3.8 patients must be treated for one to benefit (number needed to treat
Number needed to treat
The number needed to treat is an epidemiological measure used in assessing the effectiveness of a health-care intervention, typically a treatment with medication. The NNT is the average number of patients who need to be treated to prevent one additional bad outcome...
= 3.8). Click here to adjust these results for patients at higher or lower risk of CIN 2-3.
Testing in resource-poor areas
Many resource-poor areas cannot provide regular screening, and must rely on infrequent screening. A study of cervical cancer screening of 131,746 women in rural India found that a single DNA test reduced the number of advanced cervical cancers and deaths over 8 years, while a single acetic acid examination or a single Pap screening did not. However, the DNA test cost US $30–40, which was unaffordable in many regions, it is time-consuming, and requires a sophisticated laboratory infrastructure. A simple, affordable, and accurate test is being evaluated in China and other countries. The new test may become available on the market in 2010 at significantly lower cost than current tests.With HPV testing, there was a 50 percent reduction in the number of deaths from cervical cancer compared to unscreened women. Compared to other methods, the research showed the HPV testing reported the fewest false negatives.
Other options
The Bill and Melinda Gates Foundation has funded an eight-year study of a DNA test for the virus that causes cervical cancer. The test manufactured by Qiagen for a low cost per test with results available in only a few hours may allow reduction in use of annual Pap smears. The test has been shown to work "acceptably well" on women who take the swabs themselves rather than allowing a physician to test. This may improve the chances of early diagnosis for women who are unwilling to be screened due to discomfort or modesty.Visual inspection to detect pre-cancer or cancer
In areas where Pap smear screening is not available or affordable, other methods of testing have been evaluated.Visual inspection of the cervix, using acetic acid (white vinegar; VIA) or Lugol’s iodine (VILI) to highlight precancerous lesions so they can be viewed with the "naked eye", shifts the identification of precancer from the laboratory to the clinic. Such procedures eliminate the need for laboratories and transport of specimens, require very little equipment and provide women with immediate test results. A range of medical professionals—doctors, nurses, or professional midwives—can effectively perform the procedure, provided they receive adequate training and supervision. As a screening test, VIA may perform as well as or better than cervical cytology in accurately identifying pre-cancerous lesions. This has been demonstrated in various studies where trained physicians and mid-level providers correctly identified between 45% and 79% of women at high risk of developing cervical cancer. By comparison, the sensitivity of cytology has been shown to be between 47 and 62%. Cytology provides higher specificity (fewer false positives) than VIA. Like cytology, one of the limitations of VIA is that results are highly dependent on the accuracy of an individual's interpretation. This means that initial training and on-going quality control are of paramount importance. Increased false positives are particularly important in a screen-and-treat setting, since over-treatment and resulting impairment of fertility is more likely.
VIA can offer significant advantages over Pap in low-resource settings, particularly in terms of increased screening coverage, improved follow-up care and overall program quality. Due to the need for fewer specialized personnel and less infrastructure, training, and equipment, with VIA public health systems can offer cervical cancer screening in more remote (and less equipped) health care settings and can achieve higher coverage. Furthermore, providers can share the results of VIA with patients immediately, making it possible to screen and treat women during the same visit. This helps ensure that follow-up care can be provided on the spot and reduces the number of women who may miss out on treatment because they are not able to return to the clinic at another time. In a "screen and treat" project in Peru, for example, only 9% of women who screened positive failed to receive treatment in the single-visit approach, compared with 44% of women who were lost to treatment using a multi-visit model.
VIA has successfully been paired with cryotherapy, a relatively simple and inexpensive method of treating cervical lesions that can be performed by primary care physicians and mid-level providers.
How women are screened
The procedures for testing women using Pap smear, liquid-based cytology, or HPV testing are similar. A sample of cells is collected from the cervix using a spatula or small brush. The cells are then checked for any abnormalities.To take the sample of cells, the doctor or nurse puts an instrument called a speculum inside the vagina. The speculum has two arms that spread the sides of the vagina apart so that the doctor or nurse can see the cervix. Then they scrape the surface of the cervix with a spatula or small brush. This collects a sample of cells from the outer layer of the cervix.
With a Pap smear, cells collected using a spatula are smeared onto a slide for examination under a microscope. In liquid-based cytology, a sample of cells is taken using a small brush. The cells are put it into a pot of liquid, and analysed for abnormalities. Cervical cells to be tested for HPV
Human papillomavirus
Human papillomavirus is a member of the papillomavirus family of viruses that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes...
are collected in a similar way.
How abnormal cells are removed
Women may be told that they have CIN (cervical intraepithelial neoplasiaCervical intraepithelial neoplasia
Cervical intraepithelial neoplasia , also known as cervical dysplasia and cervical interstitial neoplasia, is the potentially premalignant transformation and abnormal growth of squamous cells on the surface of the cervix. CIN is not cancer, and is usually curable...
), or CIS (carcinoma in situ
Carcinoma in situ
Carcinoma in situ is an early form of cancer that is defined by the absence of invasion of tumor cells into the surrounding tissue, usually before penetration through the basement membrane. In other words, the neoplastic cells proliferate in their normal habitat, hence the name "in situ"...
) - these terms describe different levels of abnormality found in the cervical cells. Abnormal cells can be removed or destroyed using one of several different procedures.
Laser ablation and cryotherapy
Cryosurgery
Cryosurgery is the application of extreme cold to destroy abnormal or diseased tissue. The term comes from the Greek words cryo and surgery meaning "hand work" or "handiwork"....
treat just the part of the cervix that contains abnormal cells. Laser ablation uses a laser to burn away the abnormal cells, while cryotherapy uses a cold probe to freeze the cells away. These procedures allow normal cells to grow back in their place. The loop electrical excision procedure
Loop electrical excision procedure
The loop electrosurgical excision procedure is currently one of the most commonly used approaches to treat high grade cervical dysplasia discovered on colposcopic examination. In UK it is known as "large loop excision of the transformation zone" . The procedure has many advantages including low...
(called LLETZ or 'large loop excision of the transformation zone' in the UK), cervical conization
Cervical conization
Cervical conization refers to a biopsy of the cervix in which a cone-shaped sample of tissue is removed from the mucous membrane. Conization may be used either for diagnostic purposes, or for therapeutic purposes to remove pre-cancerous cells.Types include:* cold knife conization...
(or cone biopsy) and hysterectomy
Hysterectomy
A hysterectomy is the surgical removal of the uterus, usually performed by a gynecologist. Hysterectomy may be total or partial...
remove the whole area containing the cells that could become pre-cancerous or develop into cervical cancer.