Pathologist’s Corner – Dr. KB Wall on Recent Changes in Guidelines For Cervical Cancer Screening

Published October 10, 2014 – Carolyn KB Wall, M.D., FCAP

kbThe guidelines for the prevention and early detection of cervical cancer were updated in 2012. The Papanicolaou (Pap) smear or Pap test, as it should now be called since it is not only done by smear method, is a proven screening test that has saved many lives from cervical cancer death since it was implemented as part of women’s healthcare in the 1960’s.

Although the Pap test is not perfect, as no test is perfect, it has been responsible for the reduction of cervical cancer deaths. Cervical cancer used to be the most frequent cause of cancer death in American women, but now it is ranked #14 for cancer death in American women, according to cancer statistics published in 2012. It is estimated that about half of women who get cervical cancer have never had a Pap test, and another 10% did not have a Pap test within the last 5 years of their diagnosis of cervical cancer. The Pap test prevents cervical cancer by detecting the precancerous cells in the cervix so that a woman can be treated to destroy the precancerous cells before they can progress to invasive cancerous cells. Although there are other types of cervical cancer, the Pap test is most successful at preventing the squamous cell type of cervical cancer.

Medical science has shown that the high risk subtypes of the Human Papilloma Virus (HPV), especially HPV 16 and HPV 18, are the cause of cervical cancer, if the infection is persistent, and not cleared naturally by the body or by treatment. Therefore, with the development of tests for HPV that can be combined with and performed from the Pap test (“ThinPrep and SurePath” liquid-based methods), testing for HPV is part of cervical cancer screening in certain age groups of women.

When the Pap smear was first used as a screening test, there was no research to provide evidence for the best time and how often to perform the Pap, so it was arbitrarily performed every year as part of an annual visit to the gynecologist. The new guidelines are based on many years of research and the current understanding of the natural biology of HPV. They make recommendations for different screening methods and intervals according to a woman’s age group. HPV is very common in young, sexually active women, and most of the abnormal cells found on the Pap from HPV infection will resolve without treatment. When HPV is found in women aged 30 or older, it may indicate a persistent HPV infection, which puts the woman at a higher risk for developing cervical cancer. When HPV is persistent, the virus takes over the machinery of the cell and changes the cell to a dysplastic or precancer cell. The precancer is referred to as CIN3, which means Cervical Intraepithelial Neoplasia, grade 3, and also HSIL, which means High Grade Squamous Intraepithelial Lesion. If these precancerous cells are not treated, cervical cancer (squamous cell type) will eventually develop.

The purpose of the newest guidelines is to provide a strategy that is most optimal to detect cervical precancer and thereby prevent cervical cancer, but at the same time, avoid the detection of abnormal cells related to HPV infections that will resolve without treatment. Unnecessary treatment of the cervix is expensive and can lead to complications, such as premature birth, because the process of destroying the precancerous cells can increase the risk for the cervix to become incompetent to hold a pregnancy.

The following are the recommendations made by the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology to be used as guidelines for the prevention and early detection of cervical cancer and are taken verbatim from the paper with the same title (Reference: Saslow, D, Solomon, D, Lawson, HW, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology Screening Guidelines for the Prevention and Early Detection of Cervical Cancer.  American Journal of Clinical Pathology, 2012; volume 137; pages 516-542). These guidelines are only guidelines that your doctor or health care provider may take into consideration. They are not mandates or absolute requirements.  After more evidence is gathered, in the future, these guidelines will be reviewed and probably changed or updated.

Age to begin cervical cancer screening:

Should begin at age 21. Women aged younger than 21 years should not be screened regardless of the age of sexual initiation or other risk factors.

Note: Adolescents should still have access to appropriate health care. Cervical cancer prevention should focus on universal HPV vaccination.

Screening periodicity (time between screening):

Women at any age should not be screened annually by any screening method; rather,   recommended screening intervals for women are based on age and clinical history.

Women aged 21 to 29

Screening with cytology alone every 3 years is recommended.

Note: HPV testing should not be used to screen women in this age group, either as a stand-alone test or as a cotest with cytology. (This is because of the high prevalence of HPV in women younger than 30).

Women aged 30 to 65

Should be screened with cytology and HPV testing (“cotesting”) every 5 years (preferred)   or

May be screened with cytology alone every 3 years (acceptable)

Note: Cotesting has increased sensitivity for detecting CIN3+ compared with cytology alone. Women screened with cotesting also have a lower subsequent risk of CIN3+ and invasive cancer, permitting a lengthening of screening intervals (to 5 years). Extending the screening interval to 5 years reduces the detection of transient HPV infections and related lesions (HPV infections and related lesions that would resolve without treatment). Taken together, women who cotest negative are at very low risk for CIN 3 and cancer for 5 years after the negative cotest (Pap and HPV test).

Note:  The addition of HPV testing to cytology also enhances the identification of women with adenocarcinoma of the cervix (a different type of cervical cancer other than squamous cell type) and its precursors.

Management of Women with HPV-Positive, Cytology-Negative Cotests (Discordant cotest results)

HPV+Pap-

Option 1: Repeat cotesting in 12 months    or

Option 2: Immediate HPV genotype-specific testing for HPV 16 alone or for HPV16/18

Note: Women cotesting HPV positive, cytology negative should not be referred directly to colposcopy.

There are more recommendations that can seem quite complicated when there are discordant results of the “cotest”. This article will not get into the management recommendations for all of the possible abnormal results of Pap and HPV testing. One may refer to another paper for this (Reference: Massad, LS, Einstein, MH, Warner, KH, et al.  2012 Updated Consensus Guidelines , the Management of Abnormal Cervical Cancer Screening Tests and Cancer Precursors, published simultaneously in Obstetrics & Gynecology and Journal of Lower Genital Tract Disease). This paper provides your doctor or health care provider with algorithms to follow for all of the different management options as related to all of the different possible abnormal results of cervical cancer screening.

Women aged older than 65 years

No screening following adequate negative prior screening and

Once screening is discontinued it should not resume for any reason, even if a woman reports having a new sexual partner.

Note: Women with a history of CIN2 or a more severe diagnosis (CIN3 or Adenocarcinoma in situ) should continue routine screening for at least 20 years, even if this extends screening past age 65.

Note: Adequate negative prior screening is defined as 3 consecutive negative cytology results or 2 consecutive negative cotests within the 10 years before ceasing screening, with the most recent test occurring within the past 5 years.

Note: A new carcinogenic HPV infection in a woman aged 65 years or older with a cervix should clear spontaneously in most cases, and only a small percentage of women should have a persistent infection. Since the transformation zone of older women is smaller and less accessible than in younger women, and because cervical cancer develops many years after an incident infection, screening this population would detect a very small number of new cases of CIN2+ and prevent very few cervical cancers and even fewer cancer deaths.

Women who have Undergone Hysterectomy and Have No History of CIN2+ or more severe diagnosis

Women at any age following a hysterectomy with removal of the cervix who have no history of CIN2+ or a more severe diagnosis should not be screened for vaginal cancer. Evidence of adequate negative prior screening is not required. Once screening is discontinued, it should not resume for any reason, including a woman’s report of having a new sexual partner.

Note: Women who discontinue screening should continue to obtain age-appropriate preventive health care.

Screening Following HPV Vaccination

Follow age-specific recommendations (same as unvaccinated women)

Recommended screening practices should not change on the basis of HPV vaccination status.

Again, the changes in the guidelines for cervical cancer screening are not mandates or absolute requirements for your health care provider. Clinical judgment on how any individual patient should be screened, even if it deviates from the newest guidelines, is appropriate.

Note: The views and recommendations presented are not necessarily the views of the submitting author of this article.

 

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