“Much recent literature on cancer of the cervix, both European and American, has been a plea for earlier diagnosis in this common and deadly form of uterine disease. Under present conditions patients so often present themselves too late for operative relief that some hospital records show nearly as many cases turned away as are received.”
Ed Livingston: So said an article in the Feb 2, 1902 issue of JAMA entitled the “Early Diagnosis of Cervical Cancer.” In that era, cervical cancer was common and deadly. However, one of the great successes of disease screening has been for cervical cancer. Aggressive screening via pap smears and other means has made turned cervical cancer into a rare disease. Understanding its origins from HPV virus enabled even better prevention and screening strategies by vaccination against HPV, which causes cervical cancer, or screening for cervical cancer risk by detecting HPV infection.
With these successes come an increase in the complexity in cervical cancer screening strategies. In today’s episode of JAMA Clinical Reviews, we discuss Cervical Cancer Screening.
To review the complexities of cervical cancer screening we talked with an expert in the field who authored an article in the May 28, 2019 issue of JAMA on this topic. Let’s meet him.
GS: I'm George Sawaya. I'm a professor of Obstetrics Gynecology and Reproductive Sciences at the University of California San Francisco.
EL: Could you give us an overview of cervical cancer screening as it's currently recommended in the U.S.?
GS: Yes. So cervical cancer's a relatively uncommon disease in the United States due in part to the success of widespread population-based screening. Now screening works well for this particular cancer because it has a well-defined precancerous state that can be found through screening. And these precancerous changes are largely caused by human papillomavirus or HPV. And they can take many years to become cancerous. So there are lots of opportunities to find these changes through screening and to treat them. And that's how we disrupt the trajectory to cancer. Now we have three major screening strategies in the U.S. The first is familiar to everyone. It's cervical cytology or pap smears performed every three years for women ages 21 to 65. The second is that same strategy up to age 29, but then adding a test for high risk types of HPV beginning at age 30. And the third and most recent strategy is cytology performed for -- from ages 21 to 29. But then just performing the HPV test alone beginning at 30.
EL: Are there any subgroups of women or any particular groups of women that should be screened differently?
GS: Yes. All of the strategies I just mentioned are for average risk women defined as those with no prior cervical precancerous or cancerous lesions. Those who are not immunocompromised such as women living with HIV or those who have undergone solid organ transplantation. And those not exposed in utero to diethylstilbestrol. For these higher risk women, separate screening guidelines apply, and we've summarized these recommendations in a table available in the online supplement that accompanies the article. But there are also women for whom screening is not recommended. All major guideline groups recommend screening be discontinued in average risk women who have had a hysterectomy with removal of the cervix.
EL: So, given all the ways there are to screen, there is probably some confusion about how women with abnormal test results should be managed. What's your advice for clinicians about this problem?
GS: Well, you're right. The follow-up to abnormal screening test has become confusing given the numerous combinations of abnormal and normal test results. The American Society for Colposcopy and Cervical Pathology or ASCCP, has published detailed management algorithms. These can be accessed through the ASCCP website (asccp.org). We have summarized the general recommendations for managing abnormal results in a single figure in the article that we hope clinicians will find useful.
EL: There's now several different screening strategies. So how should a healthcare system or clinician or even a patient choose amongst the various strategies?
GS: Well, you're right. There's a lot to choose from. And the U.S. Preventive Services Task Force suggests that women discuss with their healthcare provider which strategy is best for them. But all busy clinicians know that the process of shared decision making is easy to evoke but can be difficult to implement especially in a time constraining visit. Now unfortunately we don't really have high quality educational tools for clinicians or women to use in understanding the tradeoffs expected with these various strategies. In its recent report, the Task Force summarized the clinical implications of choosing high risk HPV testing with or without cytology compared with choosing cytology alone. They concluded that over a lifetime of screening, the high-risk HPV testing-based strategies could be expected to avert one additional case of cervical cancer per thousand women screened compared with cytologic testing alone but would subject women to more tests and procedures.
Now we must realize that some women will not want to engage in such a deliberate process and may simply want the advice of their clinicians. And clinicians in turn may want to know which strategies are most likely to balance benefits, harms, and costs. A recent cost effectiveness analysis suggested that cytology-based screening strategies offer a good balance of benefits, harms, and costs largely due to the lower cost of cytology compared with HPV tests and the decreased likelihood of false positive testing with cytology tests. Now the U.S. Preventive Services Task Force does not consider costs in this deliberation or its recommendations. But it believes that cytology alone or high-risk HPV testing alone are preferred to using both tests together.
EL: One of the things that I learned in editing your article for JAMA was that things have changed quite a lot. It seems like cervical cancer screenings a moving target. How do you think things will change over the next few years?
GS: Well, you’re right. The field is rapidly evolving, and many changes are expected to emerge over the next few years. Novel ways to manage women with positive HPV tests will emerge to address a long-standing management conundrum. Widespread HPV vaccination is expected to decrease the incidence of cervical cancer precursors and ultimately cervical cancer. And clinicians can further the goals of cervical cancer prevention by recommending appropriate HPV vaccination. Now currently CDC recommends a two dose schedules for girls and boys initiating vaccination at ages 9 to 14. A three-dose schedule is recommended for those initiating the series at ages 15 to 26 and for those who are immunocompromised. Amid all of these exciting new changes we have to remember that many women who develop cervical cancer in the U.S. each year have never been screened or not recently screened. Now that a standalone HPV test has been approved for primary screening, self-sampling may find a place in guidelines and provide a novel way for individuals in vulnerable, marginalized, and underserved populations to have access to screening.
Increasing screening access coupled with widespread appropriate HPV vaccination may be our best approach to decreasing cervical cancer in the U.S. in the coming years.
EL: Thank you, Dr. Sawaya.
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A very special thanks to today’s guest, George F Sawaya. And thanks to Lisa Hardin who scheduled him for the podcast.
Today’s episode was produced by Daniel Morrow. Our audio team here at JAMA includes Michelle Kurzynski, Jesse McQuarters and Mike Berkwits-our Deputy editor for electronic media here at the jamanetwork
Once again I’m Ed Livingston Deputy editor for clinical reviews and education for JAMA. Thanks for listening.