Cervical cancer: Updated screening guidelines

■ Age of initial screening is 21 years for all women. Screening intervals are every 2 years for women aged 21 to 29 years and every 3 years for women aged 30 to 70 years who have had three consecutive negative results on liquid-based cytology. Discontinuation of screening is suggested for women aged 65 to 70 years who have had 3 or more consecutive negative results on cytology and no abnormal results within the preceding 10 years.

■ Women who have HIV or are immunocompromised, were exposed to diethylstilbestrol in utero, or have a
history of cervical cancer should be screened more frequently.

■ Women who received the HPV vaccine should be screened following the same protocol used for unvaccinated women.

WHO SHOULD READ THIS?


All PAs who participate in preventive health education, provide women's health care, or educate patients on cancer screening should have knowledge of the most recent guidelines.


WHY IS THIS IMPORTANT?


Over the past 30 years, the number of cervical cancers detected has declined by 50%.¹ According to the American Cancer Society, approximately 11,270 women in the United States received a new diagnosis of cervical cancer in 2009, with an estimate of 4,070 deaths. The majority of these fatalities were attributed to inadequate screening.^1-3 Sirovich and colleagues stated that, in the United States, "cases of invasive cervical cancer are more likely to represent failure to perform appropriate screening than inaccuracies of screening when performed. More than half of women who develop cervical cancer never had cervical cytology, were screened sporadically, or were not screened within the previous five years."³


In November 2009, the American College of Obstetricians and Gyne­col­ogists (ACOG) modified the cer­vical cancer screening guidelines. The goal was to minimize anxiety and expenses related to additional or unneeded testing in adolescents with an abnormal test result while continuing to maximize patient health and outcomes. Adolescents with abnormal test results usually show a spontaneous regression of the lesion(s) and do not require additional procedures. Surveillance Epidemiology and End Results 2002-2006 data show that females aged 15 to 19 years have an incidence of cervical cancer of one to two cases per million screened.³ ACOG states that clinicians should avoid procedures that could affect the cervix and potentially cause problems with childbearing in that population.¹ 


The single largest cause of cervical cancer is infection with certain strains of the human papillomavirus (HPV).¹ In a Canadian cervical cancer screening trial that involved more than 10,000 women, HPV testing had better specificity in women 30 years and older, and sensitivity in detecting cervical intraepithelial neoplasia (CIN) 2 or CIN3 was higher.³ Even though DNA testing for HPV has been available since 2003, it was not incorporated into the ACOG guidelines. The Cytopathology Education and Technology Consortium developed recommendations for HPV testing based on guidelines from the American Society for Colposcopy and Cervical Pathology and the ACS (Table: CETC HPV screening recommendations in the online version of this article). 


Seventy percent of cervical cancer risk is directly related to persistent infection with two strains of HPV: 16 and 18.⁴ Two HPV vaccines are currently available for females aged 9 to 26 years. The bivalent vaccine protects against types 16 and 18 and the quadrivalent protects against types 6, 11, 16, and 18. Continued screening is needed to identify the other 30% of oncogenic HPV types for which the vaccine provides no protection. Some health care providers are evaluating the use of HPV-DNA testing to screen for vaccine failures and to increase the time between screening tests.⁵


WHAT IS THE CURRENT SCREENING METHOD? 


ACOG suggests using the Pap smear or liquid-based cytology. Both methods involve obtaining cells from the squamocolumnar junction, which is the transformation zone or border between the cervical epithelium and the cervical columnar epithelium. For the Pap smear, the cells are placed on a slide and fixed with an alcohol-containing fixative. For liquid-based cytology, the cells are placed in a liquid fixative solution; loose cervical cells are then plated in a monolayer on glass slides. A pathologist examines the specimen for any abnormalities in the cellular characteristics.⁶ 


WHAT ARE THE ACOG's 
KEY RECOMMENDATIONS?


Age of initial screening is 21 years for all women. The previous recommendation was an initial Pap test performed within 3 years of a female becoming sexually active or at age 21 years, whichever occurred first, as cervical cancer rarely develops in younger women. With the previous ACOG guidelines, extensive surveillance was warranted for patients in this age group whose Pap smear showed signs of dysplasia, which resulted in increased cost, greater patient anxiety, and potential implications for childbearing.^1,3 


One risk of screening is adverse health effects related to procedures that are performed based on abnormal Pap smear results. A meta-analysis done in 2006 found an association between cold-knife conization or loop electrosurgical excision procedure and preterm delivery.³ Currently, ACOG recommends against treating most biopsy-confirmed precancerous lesions in women younger than 21 years. Precancerous CIN1 typically resolves on its own.³ Similarly, spontaneous regression frequently occurs with CIN2 lesions. Resolution of low grade lesions is seen after 3 years in 75% of adults and 91% of adolescents.³ CIN3 lesions are rare and may be present for 10 years before becoming invasive. 


Screening intervals are every 2 years for women aged 21 to 29 years and every 3 years for women aged 30 to 70 years who have had three consecutive negative results on liquid-based cytology. Subsequent screening can be performed via Pap smear or liquid-based cytology.¹ More frequent screening should continue in women who are HIV-positive or otherwise immunocompromised, who have been exposed to diethylstilbestrol, or who have a history of cervical cancer.^1,7 However, ACOG does not define a screening frequency for these patients. The previous recommendation was annual screening for all women.


Discontinuation of screening is suggested for women aged 65 to 70 years who have had 3 or more consecutive negative results on cytology and no abnormal results within the preceding 10 years. This recommendation is similar to other published guidelines. ACOG also recommends discontinuing routine Pap smears in women who have had a total hysterectomy for non-cancer-related reasons and have no history of CIN2 or CIN3¹ (Table: Guidelines for cervical cytology screening in the online version of this article). 


Concern is held for women older than 65 years who are deemed to be at low risk for cervical cancer because of previous normal cytology results but who currently have multiple sexual partners and presumably new sexual exposures. The new guidelines recommend continued routine screening for this group. Women older than 65 years who are not sexually active do not need continued screening. Women who present with symptoms of cancer, such as postmenopausal bleeding or pelvic pain, need a gynecologic examination. Women with a history of CIN2 or CIN3 at the time of hysterectomy with removal of the cervix should continue to be screened with a regular gynecologic examination. The frequency of these screenings has not been defined by ACOG.³ High-grade lesions are rare in women in this age group who have previously been screened. According to the previous guidelines, women who had a hysterectomy because of CIN could discontinue screening after three normal Pap smear results.³ Previously, women who had a hysterectomy with removal of the cervix could be at risk for vaginal cancer and therefore screening needed to be continued; however, case studies have proven this theory is incorrect.^3,5 


WHAT IS THE SIGNIFICANCE OF THESE CHANGES?


Controversy exists over the long-term effects of HPV vaccination on screening initiation and screening intervals. ACOG's latest guidelines suggest screening immunized women according to the same protocol used for screening nonimmunized women. Concerns have been raised that HPV-vaccinated women may neglect regular screening because of a sense of protection from the vaccination.⁵ How long immunity from the vaccination lasts is not known, but protection for at least 7.5 years has been seen.⁵ However, 30% of cervical cancer cases continue to be caused by factors other than persistent infection with HPV 16 and/or HPV 18; therefore, such a sense of security from vaccination is inappropriate. 


PAs should discuss these guideline changes with their patients. Patients should be aware that the changes are made to balance potential benefits and avoid the emotional, physical, or financial concerns that result from an abnormal test result. Clinicians should continue to educate all female patients on the importance of Pap smears and offer screening per the recommendations. JAAPA


REFERENCES


1. American College of Obstetricians and Gynecologists. First cervical cancer screening delayed until age 21. Less frequent pap tests recommended. American Congress of Obstetricians and Gynecologists Web site. http://www.acog.org/from_home/publications/press_releases/nr11-20-09.cfm. Accessed June 7, 2010.


2. American Cancer Society. Cancer facts & figures 2009. http://www.cancer.org/downloads/STT/500809web.pdf. Accessed June 7, 2010.


3. Sirovich BE, Feldman S, Goodman A. Screening for cervical cancer. UpToDate Web site [subscription database]. http://www.uptodate.com. Accessed June 16, 2010.


4. Schiffman M, Castle PE, Jeronimo J, et al. Human papillomavirus and cervical cancer. Lancet. 2007;370(9590):890-907.


5. Bauch CT, Li M, Chapman G, Galvani AP. Adherence to cervical screening in the era of human papillomavirus vaccination: how low is too low? Lancet Infect Dis. 2010;10(2):
133-137.


6. Feldman S, Crum CP, Goff B. Cervical cancer screening tests: Techniques for cervical cytology and human papillomavirus testing. UpToDate Web site [subscription database]. http://www.uptodate.com. Accessed June 16, 2010.


7. Sawaya GF. Cervical-cancer screening—new guidelines and the balance between benefits and harms. N Engl J Med. 2009;361(26):2503-2505.