In the 1940s, cervical cancer was a principal cause of death of childbearing women in the United States. Dr. George Papanicolaou was a Greek immigrant who initially began his academic career studying the reproductive cycles of guinea pigs. After moving to the United States, he held a position in the anatomy department at Cornell University. He changed his focus of study to human physiology and began collaborating with gynecological pathologist Dr. Herbert Traut. While working together at Cornell University, they published Diagnosis of Uterine Cancer by the Vaginal Pap Smear in 1943. This significant work detailed how normal and abnormal vaginal and cervical cells could be viewed under a microscope and how they should be classified. Not long after that, the Pap Smear became the gold standard in cervical cancer screening, and it is still the primary screening tool for cervical cancer today.
In the United States, death due to cervical cancer has declined by more than 60% since the 1950s. Once, one of the most frequent cancers affecting women of childbearing age, it now ranks 14th. In 2010, approximately 12,000 women were diagnosed with cervical cancer with about 4000 resulting in death. From 2002 through 2012, the rate of cervical cancer decreased by 1.3%, and deaths from cervical cancer decreased by 0.9%. In 2014, Hispanic women were reported to have the highest rate of getting cervical cancer, while African-American women had the highest rate of death from the disease.
Cervical cancer is much more common in countries without widespread screening programs. More than 80% of cervical cancer cases are found in developing countries. Cervical cancer is still the third most common cause of cancer in women worldwide. Annually, there are approximately 528,000 new cases of cervical cancer annually with 266,000 deaths. These statistics make it the second most common cause of cancer-related death in women.
In the 1980s, researchers discovered that virtually all cases of cervical cancer were caused by human papillomavirus (HPV). There are more than 100 types of HPV, and 40 can be transmitted sexually, while 15 are considered "high-risk HPV" or cancer-causing. There are two subtypes of HPV, 16 and 18, which cause about 70% of cervical cancers worldwide.
Cervical infection with high-risk HPV is usually required for the development of cervical cancer. However, HPV infection alone is not sufficient for progression to neoplasia. Most infections with high-risk HPV are transient and do not progress to cervical intraepithelial neoplasia (CIN). A small portion of women infected with high-risk HPV will develop cervical cancer. Cigarette smoking, a compromised immune system, and HIV infection are all cofactors in HPV persistence.
In 2009, the American College of Obstetricians and Gynecologists (ACOG) recommended that women begin having pap smears at the age of 21. ACOG also recommends women ages 21 to 29 should have Pap smear testing every three years. The organization noted that women ages 30 to 65 should have pap smears with HPV testing every 5 years and screening should stop after age 65. There are special populations of women who should be screened more frequently for cervical cancer than the general population. They include women infected with HIV, immunocompromised women (such as organ transplant patients), women exposed to diethylstilbestrol while in utero, and women previously treated for CIN 2, CIN 3, or cervical cancer.
In 2018 the United States Preventive Services Task Force (USPSTF) revised its recommendations. The USPSTF recommends screening for cervical cancer every 3 years with cervical cytology alone in women aged 21 to 29 years. (A recommendation) The USPSTF recommends screening every 3 years with cervical cytology alone, every 5 years with hrHPV testing alone, or every 5 years with hrHPV testing in combination with cytology (co-testing) in women aged 30 to 65 years. (A recommendation) The USPSTF recommends against screening for cervical cancer in women younger than 21 years. (D recommendation) The USPSTF recommends against screening for cervical cancer in women older than 65 years who have had adequate prior screening and are not otherwise at high risk for cervical cancer. (D recommendation) The USPSTF recommends against screening for cervical cancer in women who have had a hysterectomy with removal of the cervix and do not have a history of a high-grade precancerous lesion or cervical cancer. (D recommendation)
Women with epithelial cell abnormality on pap smear should be further tested with colposcopy and biopsy. A colposcope is a binocular microscope that allows visual inspection of the cervix. Gross abnormalities visualized on colposcopy can then be biopsied for further classification.
There are two acceptable techniques for collecting the Pap Smear: liquid-based and conventional. A clinician will place a speculum into the woman's vagina and identify the cervix. The liquid-based method involves collecting cells from the transformation zone of the cervix by using a brush and transferring the cells to a vial of liquid preservative. The conventional technique involves collecting cells from the transformation zone of the cervix by using a brush and spatula, transferring the cells to a slide, and fixing the slide with a preservative. The liquid-based technique allows testing for HPV, gonorrhea, and chlamydia from a single collection. Theoretically, the liquid-based technique has the advantages of easier interpretation, fewer unsatisfactory results, and filtering of blood and debris.
Vaginal discharge, blood, and lubricants can interfere with the interpretation of Pap smears. When performing Pap smears, many providers use either water or a small amount of water-based lubricant to minimize patient discomfort.
Since 1988, the Bethesda System for Reporting Cervical Cytology has been the accepted reporting system in the United States. The 2014 revision is the most recent.
Specimen type: Indicates whether it is conventional or liquid-based
Specimen adequacy: Indicates if it is satisfactory for evaluation or unsatisfactory for evaluation
Epithelial Cell Abnormalities
With features suspicious for invasion (if invasion suspected)
Squamous cell carcinoma
Other malignant neoplasms
Since the discovery of HPV subtypes causing most cases of cervical cancer, two vaccines have been created to decrease the number of new cervical cancer cases in the future. There is a bivalent vaccine which offers protection from HPV subtypes 16 and 18. The quadrivalent vaccine also protects users from HPV 16 and 18 but also subtypes 6 and 11 which cause 90% of genital warts. There is continuing research on vaccines for cervical cancer prevention.
A computer-aided automated device can interpret Pap smear specimens. The Bethesda System for Reporting Cervical Cytology requires documentation of the device and result if using a computer-aided system.
|The Bethesda System for Reporting Cervical Cytology: A Historical Perspective., Nayar R,Wilbur DC,, Acta cytologica, 2017 [PubMed PMID: 28693017]|
|Human Papillomavirus and Its Testing Assays, Cervical Cancer Screening, and Vaccination., Zhu Y,Wang Y,Hirschhorn J,Welsh KJ,Zhao Z,Davis MR,Feldman S,, Advances in clinical chemistry, 2017 [PubMed PMID: 28629588]|
|Cervical, Dysplasia, Cooper DB,McCathran CE,,, 2017 Jun [PubMed PMID: 28613609]|
|Cervical cytology screening among low-income, minority adolescents in New York City following the 2009 ACOG guidelines., Tsui J,Hofstetter AM,Soren K,, Preventive medicine, 2014 Jun [PubMed PMID: 24650625]|
|Cost-effectiveness of human papillomavirus vaccination in Germany., Damm O,Horn J,Mikolajczyk RT,Kretzschmar MEE,Kaufmann AM,Deleré Y,Ultsch B,Wichmann O,Krämer A,Greiner W,, Cost effectiveness and resource allocation : C/E, 2017 [PubMed PMID: 28878573]|
|Optical techniques for cervical neoplasia detection., Novikova T,, Beilstein journal of nanotechnology, 2017 [PubMed PMID: 29046833]|