Cervical screening

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Cervical screening involves a clinician taking samples of cells from the cervix. 202306 Cervical Cancer Screening.svg
Cervical screening involves a clinician taking samples of cells from the cervix.
Cervical screening assesses cellular abnormalities within the cervix, and/or looking for viral DNA. Diagram showing the transformation zone on the cervix CRUK 375.svg
Cervical screening assesses cellular abnormalities within the cervix, and/or looking for viral DNA.

Cervical cancer screening is a medical screening test designed to identify risk of cervical cancer. Cervical screening may involve looking for viral DNA, and/or to identify abnormal, potentially precancerous cells within the cervix as well as cells that have progressed to early stages of cervical cancer. [1] [2] One goal of cervical screening is to allow for intervention and treatment so abnormal lesions can be removed prior to progression to cancer. An additional goal is to decrease mortality from cervical cancer by identifying cancerous lesions in their early stages and providing treatment prior to progression to more invasive disease. [1]

Contents

Currently available screening tests fall into three categories: molecular, cytologic and visual inspection. Molecular screening tests includes nucleic acid amplification tests (NAAT), which identify high risk human-papilomma virus (HPV) strains. Cytologic tests include conventional Pap smear and liquid based cytology. Visual Inspection tests involve application of a solution to enhance identification of abnormal areas and can utilize the naked eye or a colposcope/magnifying camera. [3]

Medical organizations of different countries have unique guidelines and screening recommendations. The World Health Organization has also published guidelines to increase screening and improve outcomes for all women taking into consideration differences in resource availability of regions. Management of abnormal screening results can include surveillance, biopsy, or removal of the suspicious region via surgical intervention. Diagnosis of more advanced cancer stages may require other treatment options such as chemotherapy or radiation. [2]

General screening procedure

Sample collection for thin-prep-cytology from the cervix uteri of a 39-years-old multiparous woman. The cervical brush is visible just before entering the cervix uteri. Taking pap-smear 1.png
Sample collection for thin-prep-cytology from the cervix uteri of a 39-years-old multiparous woman. The cervical brush is visible just before entering the cervix uteri.
Brush utilized in cervical screening exams to collect samples. Journal.pone.0026395.g001 cervical cytology brushes.png
Brush utilized in cervical screening exams to collect samples.

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. [4]

To take the sample of cells, the health care clinician inserts an instrument, called a speculum, inside the vagina. The speculum has two arms that spread the walls of the vagina apart in order to 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. [4]

Self-collection is also an option when testing by a provider is unavailable or uncomfortable for a patient. When utilizing HPV testing, self-collection has been shown to be as accurate as swabbing by a provider. This equality has not been demonstrated for other testing such as pap smear or liquid-based cytology. [1] [2]

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 into a container of liquid, and analysed for abnormalities. Cervical cells to be tested for HPV are collected in a similar way. [5]

Types of screening

Molecular

Molecular testing identifies an infection called human papillomavirus, or HPV. Human papillomavirus (HPV) infection is a cause of nearly all cases of cervical cancer. [6] 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. [7]

The screening process utilizes nucleic acid amplification testing to look for DNA or RNA of the virus present within cervical cells. Some tests can identify up to 14 different types of high risk strains. [2]

Accuracy of HPV testing report:

Cytologic

Conventional Pap smear

Normal cervical cells in a Pap smear Normal PAP (Cervical) Smear.jpg
Normal cervical cells in a Pap smear

In the conventional Pap smear, the collected cells are smeared on a microscope slide, and a fixative is applied. The slide is evaluated in a pathology lab to identify cellular abnormalities.

Accuracy of conventional cytology report: [10]

Liquid-based monolayer cytology

In liquid based monolayer cytology, the collected cells are placed into a liquid medium. The sample is evaluated in a pathology lab to evaluate cellular abnormalities.

Accuracy of liquid based monolayer cytology report: [10]

Visual inspection

Visual inspection involves the application of ascetic acid or lugol's iodine solution to the cervix. These solutions highlight abnormal areas for easier identification with the naked eye. A magnifying camera called a colposcope can also be utilized for clearer viewing when available. [2]

Combination testing (co-testing)

Combination testing or co-testing, is when individuals receive both molecular high risk HPV testing and cytology. [11] These results can be utilized to calculate the patient's immediate risk for cervical intraepithelial neoplasia grade 3 or cancer (CIN3+). [12]

The calculated risk can be used to recommend appropriate follow-up options.[ citation needed ]

Recommendations

Different countries and medical organizations have specific cervical screening recommendations to guide patient care.

World Health Organization

In 2021 the World Health Organization published the second edition of WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention. Within this publication they outline 23 recommendations addressing differences in guidelines for women living with or without HIV. The quality of evidence is rated strong, moderate, low or very low. Some of the recommendations are included below, this is not a comprehensive list. [2]

Europe

Most countries suggest or offer screening between the ages of 25 and 64. [13] According to the 2015 European guidelines for cervical cancer screening, routine HPV primary screening should not begin under 30 years of age. Primary testing for oncogenic HPV can be used in a population-based programme for cervical cancer screening. [14] In England, the NHS cervical screening programme is available to women aged 25 to 64; women aged 25 to 49 receive an invitation every 3 years and women aged 50 to 64 receive an invitation every 5 years to undergo HPV testing. [15] [16] If there is a positive HPV test result, then patients undergo further cytology (Pap smear). [15]

United States

Screening is recommended for women between ages 21 and 65, regardless of age at sexual initiation or other high-risk behaviors. [17] [18] [19] For healthy women aged 21–29 who have never had an abnormal Pap smear, cervical cancer screening with cervical cytology (Pap smear) should occur every 3 years, regardless of HPV vaccination status. [11] The preferred screening for women aged 30–65 is "co-testing", which includes a combination of cervical cytology screening and HPV testing, every 5 years. [11] However, it is acceptable to screen this age group with a Pap smear alone every 3 years or with an FDA-approved primary high risk HPV test every 5 years. [11] In women over the age of 65, screening for cervical cancer may be discontinued in the absence of abnormal screening results within the prior 10 years and no history of high-grade lesions. [11] Management of screening results is based on recommendations by the American College of Obstetricians and Gynecologists and other professional organizations. [12]

Australia

Screening is offered to women aged 18–70, every two years. This is by Pap smear, and regardless of sexual history. [20] [ needs update ] In Canada, where screening programmes are arranged at provincial level, the general recommendation is not to begin routine screening until the age of 25 in the absence of specific reasons to, then to screen every three years until the age of 69. [21] In Ontario, "The Ontario Cervical Screening Program recommends that women who are or have been sexually active have a Pap test every 3 years starting at age 21." [22]

Thailand

The Ministry of Public Health recommends women from age 30-60 receive primary HPV testing every 5 years. Based on the results of the test, those with higher risk strains of HPV will be referred for colposcopy, while those with lower risk strains will be referred for cytology. [23]

Management of screening results

Screening results are generally categorized as normal or abnormal. Women who receive an abnormal test result will be guided on their next recommended steps by their healthcare provider. Management is significantly impacted based on the type of testing done, and the severity of the abnormality. Some of the follow-up options include surveillance, histological diagnosis via colposcopy/biopsy, or removal of the abnormal tissue via an ablative or surgical method. [2]

The World Health Organization outlines two different approaches to cervical screening and follow-up. They are the Screen and Treat; and the Screen, Triage and Treat. Patient preferences, healthcare access and system resources are factors that play a role in which approach providers will recommend to their patients. [2]

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 abnormal cells. [24]

Emerging technologies

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. [25]

VIA, one of the alternative approaches to conventional testing, has shown to have a low specificity compared to cytology and a high rate of false positives in several studies. [26] [27] [28] [29] Entities such as inflammation, cervical condyloma and leukoplakia can give false positive results of VIA test. [30] There is no permanent record of the test to be reviewed later. Between community centers high variability has been observed, and even in a study of Nigeria of 2013 VIA was not reproducible nor sensitive; this led to discouraging the method in that country. [31]

In addition, p16/Ki-67 are emerging biomarkers that have been used as a triage method for HPV-positive patients. In studies conducted so far, p16/Ki-67 dual staining had a higher sensitivity and specificity compared to cytology. Using these biomarkers may help in reducing the number of false-positive tests and unnecessary examinations. [32]

Assessing DNA methylation patterns in individuals with HPV is also an emerging screening method. There are about 80 methylation patterns that can serve as potential biomarkers for cervical cancer. Molecular testing of DNA methylation patterns is more objective than cytology testing and can be automated, requiring less training with more precision. [32]

Vaginal and urine self-sampling have shown promising results in detecting the signs of cervical cancer. They also offer a more environmentally friendly alternative to in-person screening. [33] [34]

See also

Related Research Articles

<span class="mw-page-title-main">Cervix</span> Lower part of the uterus in the female reproductive system

The cervix or cervix uteri is a dynamic fibromuscular sexual organ of the female reproductive system that connects the vagina with the uterine cavity. The human female cervix has been documented anatomically since at least the time of Hippocrates, over 2,000 years ago. The cervix is approximately 4 cm long with a diameter of approximately 3 cm and tends to be described as a cylindrical shape, although the front and back walls of the cervix are contiguous. The size of the cervix changes throughout a woman's life cycle. For example, during the fertile years of a woman's reproductive cycle, females tend to have a larger cervix vis á vis postmenopausal females; likewise, females who have produced offspring have a larger sized cervix than females who have not produced offspring.

<span class="mw-page-title-main">Pap test</span> Cervical screening test to detect potential cancers

The Papanicolaou test is a method of cervical screening used to detect potentially precancerous and cancerous processes in the cervix or, more rarely, anus. Abnormal findings are often followed up by more sensitive diagnostic procedures and, if warranted, interventions that aim to prevent progression to cervical cancer. The test was independently invented in the 1920s by the Greek physician Georgios Papanikolaou and named after him. A simplified version of the test was introduced by the Canadian obstetrician Anna Marion Hilliard in 1957.

<span class="mw-page-title-main">Cervical cancer</span> Cancer arising from the cervix

Cervical cancer is a cancer arising from the cervix or in the any layer of the wall of the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal vaginal bleeding, pelvic pain or pain during sexual intercourse. While bleeding after sex may not be serious, it may also indicate the presence of cervical cancer.

<span class="mw-page-title-main">Human papillomavirus infection</span> Human disease

Human papillomavirus infection is caused by a DNA virus from the Papillomaviridae family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and results in either warts or precancerous lesions. These lesions, depending on the site affected, increase the risk of cancer of the cervix, vulva, vagina, penis, anus, mouth, tonsils, or throat. Nearly all cervical cancer is due to HPV, and two strains – HPV16 and HPV18 – account for 70% of all cases. HPV16 is responsible for almost 90% of HPV-positive oropharyngeal cancers. Between 60% and 90% of the other cancers listed above are also linked to HPV. HPV6 and HPV11 are common causes of genital warts and laryngeal papillomatosis.

<span class="mw-page-title-main">Cytopathology</span> A branch of pathology that studies and diagnoses diseases on the cellular level

Cytopathology is a branch of pathology that studies and diagnoses diseases on the cellular level. The discipline was founded by George Nicolas Papanicolaou in 1928. Cytopathology is generally used on samples of free cells or tissue fragments, in contrast to histopathology, which studies whole tissues. Cytopathology is frequently, less precisely, called "cytology", which means "the study of cells".

<span class="mw-page-title-main">Colposcopy</span> Medical examination of the cervix

Colposcopy is a medical diagnostic procedure to visually examine the cervix as well as the vagina and vulva using a colposcope.

<span class="mw-page-title-main">Anal cancer</span> Medical condition

Anal cancer is a cancer which arises from the anus, the distal opening of the gastrointestinal tract. Symptoms may include bleeding from the anus or a lump near the anus. Other symptoms may include pain, itchiness, or discharge from the anus. A change in bowel movements may also occur.

<span class="mw-page-title-main">Cervical intraepithelial neoplasia</span> Medical condition

Cervical intraepithelial neoplasia (CIN), also known as cervical dysplasia, is the abnormal growth of cells on the surface of the cervix that could potentially lead to cervical cancer. More specifically, CIN refers to the potentially precancerous transformation of cells of the cervix.

<span class="mw-page-title-main">Koilocyte</span> Type of cell that has been changed by HPV

A koilocyte is a squamous epithelial cell that has undergone a number of structural changes, which occur as a result of infection of the cell by human papillomavirus (HPV). Identification of these cells by pathologists can be useful in diagnosing various HPV-associated lesions.

Vaginal cancer is an extraordinarily rare form of cancer that develops in the tissue of the vagina. Primary vaginal cancer originates from the vaginal tissue – most frequently squamous cell carcinoma, but primary vaginal adenocarcinoma, sarcoma, and melanoma have also been reported – while secondary vaginal cancer involves the metastasis of a cancer that originated in a different part of the body. Secondary vaginal cancer is more common. Signs of vaginal cancer may include abnormal vaginal bleeding, dysuria, tenesmus, or pelvic pain, though as many as 20% of women diagnosed with vaginal cancer are asymptomatic at the time of diagnosis. Vaginal cancer occurs more frequently in women over age 50, and the mean age of diagnosis of vaginal cancer is 60 years. It often can be cured if found and treated in early stages. Surgery alone or surgery combined with pelvic radiation is typically used to treat vaginal cancer.

Colin Robert Andrew Laverty was an Australian medical practitioner and was the first to confirm that the human papillomavirus was much more common in the cervix than previously thought and, in 1978, he suggested that this virus be considered as possibly involved in the causation of cervical cancer. He was also a prolific art collector.

HspE7 is an investigational therapeutic vaccine candidate being developed by Nventa Biopharmaceuticals for the treatment of precancerous and cancerous lesions caused by the human papillomavirus (HPV). HspE7 uses recombinant DNA technology to covalently fuse a heat shock protein (Hsp) to a target antigen, thereby stimulating cellular immune system responses to specific diseases. HspE7 is a patented construct consisting of the HPV Type 16 E7 protein and heat shock protein 65 (Hsp65) and is currently the only candidate using Hsp technology to target the over 20 million Americans already infected with HPV.

An anal Pap smear is the anal counterpart of the cervical Pap smear. It is used for the early detection of anal cancer. Some types of human papillomavirus (HPV) can cause anal cancer. Other HPV types cause anogenital warts. Cigarette smokers, men who have sex with men, individuals with a history of immunosuppression and women with a history of cervical, vaginal and vulval cancer are at increased risk of getting anal cancer. Vaccination against HPV before initial sexual exposure can reduce the risk of anal cancer.

The Bethesda system (TBS), officially called The Bethesda System for Reporting Cervical Cytology, is a system for reporting cervical or vaginal cytologic diagnoses, used for reporting Pap smear results. It was introduced in 1988 and revised in 1991, 2001, and 2014. The name comes from the location of the conference, sponsored by the National Institutes of Health, that established the system.

Cervicography is a diagnostic medical procedure in which a non-physician takes pictures of the cervix and submits them to a physician for interpretation. Other related procedures are speculoscopy and colposcopy. The procedure is considered a screening test for cervical cancer and is complementary to Pap smear. The technique was initially developed by Adolf Stafl, MD, of Medical College of Wisconsin in 1981.

<span class="mw-page-title-main">Cervical cancer staging</span> Medical condition

Cervical cancer staging is the assessment of cervical cancer to determine the extent of the spread of cancer beyond the cervix. This is important for determining how serious the cancer is and to create the best treatment plan.

<span class="mw-page-title-main">Liquid-based cytology</span> Method of preparing samples for cytopathology

Liquid-based cytology is a method of preparing samples for examination in cytopathology. The sample is collected, normally by a small brush, in the same way as for a conventional smear test, but rather than the smear being transferred directly to a microscope slide, the sample is deposited into a small bottle of preservative liquid. At the laboratory, the liquid is treated to remove other elements such as mucus before a layer of cells is placed on a slide.

A well-woman examination is an exam offered to women to review elements of their reproductive health. The exam includes a breast examination, a pelvic examination and a Pap smear but may include other procedures. Hospitals employ strict policies relating to the provision of consent by the patient, the availability of chaperones at the examination, and the absence of other parties.

Microglandular hyperplasia (MGH) of the cervix is an epithelial benign abnormality (lesion) associated with gland proliferation. It can terminate in mature squamous metaplasia, and it is suspected reserve cells are involved in this process, perhaps in the form of reserve cell hyperplasia with glandular differentiation.

<span class="mw-page-title-main">Gynecologic cancer disparities in the United States</span>

Gynecologic cancer disparities in the United States refer to differences in incidence, prevalence, and mortality from gynecologic cancers between population groups. The five main types of gynecologic cancer include cervical cancer, ovarian cancer, endometrial cancer, vaginal cancer, and vulvar cancer. For patients with these and other gynecologic malignancies within the United States, disparities across the care continuum by socioeconomic status and racial/ethnic background have been previously identified and studied. The causes behind these disparities are multifaceted and a complex interplay of systemic differences in health as well as individual patient factors such as cultural, educational, and economic barriers.

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