Screening for Cervical Cancer with Human Papillomavirus (HPV) Testing

The American Cancer Society Cancer Action Network (ACS CAN) appreciates the opportunity to provide comments on the Centers for Medicare and Medicaid Services’ (CMS’) proposed decision memo for screening for cervical cancer with human papillomavirus (HPV) testing. CMS proposes that there exists sufficient evidence to add HPV testing once every five years as an additional preventive service benefit under the Medicare program for asymptomatic beneficiaries aged 30 to 65 in conjunction with the Pap test.

ACS CAN, the nonprofit, nonpartisan advocacy affiliate of the American Cancer Society, supports evidence-based policy and legislative solutions designed to eliminate cancer as a major health problem. As the nation’s leading advocate for public policies that are helping to defeat cancer, ACS CAN ensures that cancer patients, survivors, and their families have a voice in public policy matters at all levels of government.

In 2015 an estimated 12, 900 cases of invasive cervical cancer are expected be diagnosed and an estimated 4,100 women are expected to die from cervical cancer.¹ While women over the age of 50 have seen a 1.1 percent decrease in mortality, death rates have stabilized in women younger than 50.

HPV Screening

Screening tests offer the ability to identify and remove precancerous cervical lesions before they turn cancerous as well as to detect cervical cancer at an earlier stage when treatment is most successful. ACS CAN is pleased CMS’ proposed coverage determination will be more in line with the USPSTF recommendations. The USPSTF recommends a grade “A” screening for cervical cancer in women age 21 to 65 years with cytology (Pap test) every 3 years, or for women age 30 to 65 years who want to lengthen the screening interval, screening with a combination of cytology and HPV testing every 5 years.

The American Cancer Society guidelines recommend that beginning at the age of 30 women should receive a Pap smear combined with an HPV test every five years. This “co-testing” should continue until the age of 65.² Studies show that HPV testing detects more cancers, more advanced precancers earlier, and detects a second type of cervical cancer (called adenocarcinoma) that Pap tests usually miss. HPV testing provides added reassurance to women who test negative—compared to Pap tests alone. The number of colposcopies is also less for co-testing than for cytology alone when the screening interval is extended. For this reason, the American Cancer Society recommends co-testing as the “preferred” screening strategy while cytology alone is “acceptable.”³ The American Congress of Obstetricians and Gynecologists has endorsed the same guideline, including recommending co-testing as the “preferred” screening strategy. The guideline recommendations were based on an extensive evidence review including over 12,000 published scientific articles. The Society worked in collaboration with 25 organizations involved in cervical cancer screening as part of the guideline development process.

Cervical Cancer Screening in Older Women

We support CMS’ proposed coverage determination for women aged 30 to 65. Cervical cancer is a problem for older women who have not previously been screened. We urge CMS to consider expanding the proposed coverage determination to include women over age 65, who have a cervix, and who have previously not been adequately screened. Adequate screening is defined by the American Cancer Society, United States Preventive Services Task Force (USPSTF), American Congress of Obstetricians and Gynecologists, and others as follows:

Adequate negative prior screening is defined as three consecutive negative cytology results or two consecutive negative co-tests within the last ten years before ceasing screening, with the most recent test being within the past five years.

Following spontaneous regression or appropriate management of cervical intraepithelial neoplasia grade 2 (CIN2), cervical intraepithelial neoplasia grade 3 (CIN3), or adenocarcinoma in situ (AIS), routine screening should continue for at least twenty years even if this extends screening past age 65.

At the same time, we want to avoid unnecessary screening. The USPSTF recommends against screening for cervical cancer in women older than age 65 years who have been adequately screened and are not otherwise at high risk for cervical cancer. Unfortunately millions of older women continue to be unnecessarily screened each year. Therefore we believe that it is important to not continue screening moderate-risk women age 65 and older who previously have been screened.

Conclusion

On behalf of the American Cancer Society Cancer Action Network we thank you for the opportunity to comment the proposed coverage determination. If you have any questions, please feel free to contact me or have your staff contact Anna Schwamlein Howard, Policy Principal, Access and Quality of Care at Anna.Howard@cancer.org or 202-585-3261.

1 American Cancer Society, Cancer Facts & Figures 2015, available at http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2015/.
2 American Cancer Society Guidelines for the Prevention and Early Detection of Cervical Cancer, available at http:Uwww.cancer.org/cancer/cervicalcancer/ moreinformation/cervicalcancerpreventionandearlydetection/cervical-cancer-prevention-and-early-detection-cervical-cancer-screening-guidelines.
3 Saslow, D., Solomon, D., Lawson, H. W., Killackey, M., Kulasingam, S. L., Cain, J., Garcia, F. A. R., Moriarty, A. T., Waxman, A. G., Wilbur, D. C., Wentzensen, N., Downs, L. S., Spitzer, M., Moscicki, A.-B., Franco, E. L., Stoler, M. H., Schiffman, M., Castle, P. E., Myers, E. R. and ACS-ASCCP-ASCP Cervical Cancer Guideline Committee (2012), 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. CA: A Cancer Journal for Clinicians, 62: 147-172. doi: 10.3322/caac.21139.

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May 11, 2015

Tamara Syrek Jensen, JD
Director, Coverage and Analysis Group
Centers for Medicare & Medicaid Services
7500 Security Boulevard
Baltimore, MD 21244

RE: Screening for Cervical Cancer with Human Papillomavirus Testing (CAG-00442N)

Dear Ms. Syrek Jensen,

On behalf of the American Academy of Family Physicians (AAFP), which represents 120,900 family physicians and medical students across the country, I write in response to the proposed decision memo for screening for cervical cancer with human papillomavirus (HPV) testing posted by the agency on April 16, 2015.

The AAFP strongly supports this proposal and applauds CMS for the speed in issuing it. As stated in our April 24, 2014 letter and December 17, 2014 letter both on this topic, we support Medicare coverage for this important preventive service. This proposed coverage is consistent with the AAFP's recommendation for cervical cancer screening and in agreement with the United States Preventive Services Task Force’s recommendation to cover cervical cancer screening with cytology (pap smear) every 3 years for women 21-65 years of age and an option for women 30-65 to spread screening out to every 5 years with a combination of cytology and HPV testing. The combination of cytology with HPV testing allows women the choice to have less frequent screening without increasing their risk of developing cervical cancer.

The proposal is consistent with the evidence and allows women and their physicians more options for cervical cancer screening.

For any questions you might have please contact Robert Bennett, Federal Regulatory Manager, at 202-232-9033 or rbennett@aafp.org.

Sincerely,

Reid B. Blackwelder, MD, FAAFP
Board Chair

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May 1, 2015

Tamara Syrek Jensen, JD
Director, Coverage and Analysis Group
Joseph Chin, MD, MS
Acting Deputy Director, Coverage and Analysis Group
Centers for Medicaid & Medicare Services
7500 Security Boulevard
Mailstop: S3-02-01
Baltimore, MD 21244

RE: Proposed Decision Memo for Screening for Cervical Cancer with Human Papillomavirus (HPV) Testing (CAG-00442N)

Dear Ms. Syrek Jensen and Dr. Chin:

I am writing on behalf of Roche Diagnostics Corporation (RDC), a member of the Roche Group and a world leader in invitro diagnostics and tissue-based cancer diagnostics. RDC appreciates the opportunity to comment on the proposed decision memo from the Centers for Medicare & Medicaid Services (CMS) on Screening for Cervical Cancer with Human Papillomavirus (HPV) Testing (CAG-00442N). We strongly agree with CMS’ proposed decision to expand coverage for cervical cancer screening to include HPV testing in conjunction with the Pap smear test. We urge CMS to finalize its decision as proposed, including requiring that covered tests be approved or cleared by the U.S. Food and Drug Administration (FDA).

RDC is a committed to developing diagnostic tools that enable tangible improvements in the health, quality of life, and survival of patients and particularly in the area of cervical cancer prevention and women’s health. On April 20, 2011, RDC received approval from the FDA for the cobas®¹ 4800 HPV test (cobas HPV Test), which identifies women at highest risk for developing cervical cancer. The cobas HPV Test is the only FDA-approved cervical cancer screening test that identifies genotypes 16 and 18, the two highest-risk HPV genotypes responsible for more than 70 percent of cervical cancer cases, while simultaneously detecting 12 other high risk HPV genotypes.

In 2011, the FDA approved the cobas HPV Test for screening patients age 21 and older with abnormal cervical cytology results and for use adjunctively with normal cervical cytology in women ages 30 and over to assess the presence or absence of high-risk HPV genotypes. On April 24, 2014, the FDA also approved the cobas HPV Test as a first-line primary screening test for cervical cancer in women age 25 and older.

In its decision memo, CMS proposes to provide Medicare coverage of HPV testing in conjunction with Pap smear testing once every five years as an additional preventive service benefit for asymptomatic beneficiaries aged 30 to 65 years. CMS proposes to cover screening for cervical cancer with the appropriate FDA approved/cleared laboratory tests, used consistent with FDA approved labeling, and in compliance with the Clinical Laboratory Improvement Act (CLIA) regulations. We concur with the proposed decision memo and highly recommend that CMS finalize the national coverage determination as proposed, including limiting coverage to FDA approved/cleared tests. To achieve the benefits expected of cervical cancer screening, we believe it is critical that the test used to screen patients have been demonstrated to provide a correct, reliable result.

We also urge CMS to continue to monitor developments in the field of cervical cancer screening. As noted above, the cobas HPV Test was recently approved for primary screening, the first and only HPV test approved by the FDA for such indication. This approval gives physicians and patients another option to consider in screening for cervical cancer. As the medical community adapts to this and other innovations, we urge CMS to use its statutory authority to ensure beneficiaries have access to latest recommended preventive services.

Thank you for the opportunity to comment. Please contact me at alan.wright@roche.com or Kate Claessens at kathleen.claessens@roche.com if you have any questions.

Sincerely,

Alan T. Wright, M.D., M.P.H.
Chief Medical Officer
Roche Diagnostics Corporation

cc:
Kathleen Claessens, MSN, RN
Senior Director, Health Policy & Reimbursement
Roche Diagnostics Corporation

1 cobas is a trademark of Roche

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I write in support of covering Pap + HPV every 5 years for cervical cancer screening in women 30-65 yo. Please note that if the Pap is normal but the HPV is positive, the follow up recommendation is for repeat Pap + HPV in 12 months, and if that's negative, repeat contesting in 3 years. Policy should allow the recommended follow up intervals, and not just once every 5 years regardless of result. This may require additional coding from the provider to indicate this is follow up of abnormal screening, which is reasonable.

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The DES Community requests that In Utero Exposure to the drug Diethylstilbestrol (DES) be added to the screening for cervical Cancer in this proposed CMS decision memo. Due to in utero exposure to the drug DES, a carcinogen and teratogen, DES Daughters and now DES Granddaughters are at a higher risk for developing cervical cancer as well as other reproductive cancers. I am attaching a NCI reference: http://www.cancer.gov/cancertopics/causes-prevention/risk/hormones/des-fact-sheet

While screening for HPV is important, it is important that the government and the medical community do not forget the millions of DES exposed women in this country and the screening they need. Too many have forgotten the victims of The DES Tragedy!

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As a physician assistant (working in ob/gyn for 11 years) and member of ASCCP (the organization that creates cervical cancer screening guidelines), I feel it is imperative for us to be able to perform high risk HPV testing on our patients who have Medicare. Failure to do so makes us unable to adequately triage and evaluate ASCUS cytology results (a very common result in the postmenopausal population). Because the presence or absence of high risk HPV creates two completely different clinical scenarios, the absence of HPV testing in these women creates a risk of both underevalation and overtreatment. Further, it prevents us from picking up women with a potentially dangerous strain of HPV who continue to have normal cytology. We also see plenty of women under the age of 65 who have Medicare as their primary insurance. In this population where HPV continues to be prevalent, and in our resource rich society, it is truly a failure if we cannot offer these women adequate cervical cancer screening with the addition of HPV testing.

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As a Cytotechnologist, Lab Manager and educator for over 37 I am opposed to Primary HPV screening at 5 year intervals. The HPV vaccination campaign used the motto "Just one." Isn't saving "just one" life with 3 year intervals of Paps and HPV co-testing worth it, too? Here is data to support my argument and plea to endorse pap and HPV co-testing at 3 year intervals:

Comparison of cervical cancer screening results among 256,648 women in multiple clinical practices.
Blatt AJ1, Kennedy R, Luff RD, Austin RM, Rabin DS.
Author information
Abstract
BACKGROUND:
In the United States, human papillomavirus (HPV) and Papanicolaou (Pap) testing (cotesting) for cervical screening in women ages 30 to 65 years is the preferred strategy, and cytology alone is acceptable. Recently, a proprietary automated test for identifying high-risk HPV types for primary cervical screening was approved by the US Food and Drug Administration. The objective of the current study was to document extensive cervical screening among these screening options.
METHODS:
To investigate the sensitivity of various testing options for biopsy-proven cervical intraepithelial neoplasia grade 3 or worse (=CIN3) and cancer, the authors reviewed 256,648 deidentified results from women ages 30 to 65 years at the time of cotest who had a cervical biopsy specimen obtained within 1 year of the cotest.
RESULTS:
A positive cotest result was more sensitive (98.8%; 4040 of 4090 cotests) for diagnosing =CIN3 than either a positive HPV-only test (94%; 3845 of 4090 HPV-only tests) or a positive Pap-only test (91.3%; 3734 of 4090 Pap-only tests; P? CONCLUSIONS:
Compared with HPV-only testing, cotesting was more sensitive for the detection of =CIN3 in women ages 30 to 65 years. The current data suggest that approximately 19% of women with cervical cancer may be misdiagnosed by an HPV-only cervical screen. It is important to consider these data as the guidelines for cervical cancer screening undergo revision. Cancer (Cancer Cytopathol) 2015. © 2015 The Authors. Cancer Cytopathology published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
© 2015 The Authors. Cancer Cytopathology published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Another source:

In conclusion, we believe that the option of screening with: 1) cotesting with cytology and a U.S. Food and Drug Administration–approved HPV test at 3-year intervals or 2) U.S. Food and Drug Administration– approved primary HPV testing at 3-year intervals should be available to all patients and providers who want to maintain a level of cervical cancer protection similar to what was previously available with annual cytology. None of the data that have emerged since the guidelines were published have served to change our opinion that the option of better protection should be an acceptable choice for those who prefer it. Ideally the advent of molecular screening should be used to permit previous levels of cancer protection with fewer visits and procedures rather than heralding an increase in cancer risk.

© 2015 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins.
ISSN: 0029-7844/15
MS NO: ONG-14-1370
VOL. 125, NO. 2, FEBRUARY 2015

Another source:

Obstet Gynecol. 2015 Feb;125(2):311-5. doi: 10.1097/AOG.0000000000000632.
Increased cervical cancer risk associated with screening at longer intervals.
Kinney W1, Wright TC, Dinkelspiel HE, DeFrancesco M, Thomas Cox J, Huh W.
Author information

Abstract

The 2012 national recommendations for cervical cancer screening will produce a lower level of cervical cancer protection than previously afforded by annual cytology or 3-year cotesting. After a single negative cotest result, the risk of cervical cancer is twice as large at 5 years as it is at 3 years. Modeling published since the 2012 guidelines were drafted indicates that extending the cotesting screening interval from 3 to 5 years at ages 30-64 years will result in an additional 1 woman in 369 compliant with screening receiving a cervical cancer diagnosis during her lifetime, and an additional 1 in 1,639 dying of cervical cancer. The authors believe that a significant number of patients and providers would not choose to accept these additional risks if they understood them, despite the recognition of potential harms associated with more intensive screening.

PMID: 25568989 [PubMed - in process]

In conclusion, I believe there is sufficient data to support the continued use of Pap and HPV co-testing at a maximum of 3 year intervals. Please, lets save "just one" more life. Young women in their twenties and thirties will die from cervical cancer leaving behind small children and loved ones and the opportunity to be vital members of our society. Cervical cancer screening is one of the least expensive screening tests we have. Treating cervical cancer will come at a much higher cost. Thank you.

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The work done on this issue is commendable. It seems reasonable that co-testing should be used to continue to decrease ICC mortality. The 5-year period for subsequent testing, however, raises some questions.

According to the data, there were over 4000 deaths from ICC in 2014. That would imply that the number of diagnosed patients was much higher, assuming that everyone diagnosed with ICC does not die from it. But even if it were so, that would mean 50% of those who died were previously screened and that 90% of them were screened within 5 years. This would suggest that co-testing, although a great tool to detect pre-cancerous lesions, can be much more efficient in saving lives if performed more frequently than every 5 years. Unless, of course, 2000 deaths are deemed acceptable or negligible.

The recent study by Quest Diagnostics has shed some light on the accuracy and specificity of HPV testing and pap smear screening. A consideration of their findings might serve as a guide in moving forward with the new recommendations.

Moreover a 5-year period would place high-risk patients at a disadvantage. That is, one could have a negative co-testing (assuming that it is a true negative). She could contract HPV within the same year and would not be treated until 5 years later. No need to mention the adenocarcinomas (EC and EM) that do not shed readily and may not be reflected on a particular Pap-smear.

If these issues can be addressed adequately and one may prove that they do not pose great threats to women, then the recommendations as they are reflect a wise approach to caring for women.

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As a cytotechnologist and patient, I strongly urge CMS to reconsider it's decision and recommend that a 3-year interval is much safer and has a lower cumulative risk for CIN III and ICC than a 5-year interval. If you look at data from Gage, et al JNCL 2014 there is a 54% increase in cumulative risk of CIN III at 5 years compared to 3, and a 50% increase in risk of ICC at 5 years with co-testing. This population is also at increased risk for endometrial cancer and although the pap isn't designed as a screening tool for this disease, every lab finds several every year. As more and more clinicians have been adopting co-testing and using a 3-year interval in recent years the rate of ICC continues to fall. What we're doing is working. Thank you for your consideration in approving a 3-year interval.

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This recent publication is a good rationale for co-testing every 3 years instead of every 5 years as CMS is proposing and and suggested by the USPTF.

http://www.ncbi.nlm.nih.gov/pubmed/25568989
"After a single negative cotest result, the risk of cervical cancer is twice as large at 5 years as it is at 3 years. Modeling published since the 2012 guidelines were drafted indicates that extending the cotesting screening interval from 3 to 5 years at ages 30-64 years will result in an additional 1 woman in 369 compliant with screening receiving a cervical cancer diagnosis during her lifetime, and an additional 1 in 1,639 dying of cervical cancer."

Why would be knowingly put human lives at stake? It was been proven that we can adequately screen and save lives by continuing to co-test for cervical cancer every three years.

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This proposal is, in my medical opinion, criminal.
A woman who changes sexual partners within this age frame (30-65) is subject to HPV infection, both high risk and low risk. To think that she can go for 5 years without a Pap test while being sexually active and exposed- is a very misguided idea.
Are any of the people involved in this decision actually WORKING as OB/GYN's, cytopathologists or nurse practitioners with a high risk population?? I didn't think so.
The rate of CIN III has ALREADY been going up because of the three-year change in screening "guidelines". Also- 19% of lesions are going UNDETECTED because of HPV DNA screening alone.

THE PUBLIC NEEDS TO WAKE UP AND TELL CMS AND INSURANCE COMPANIES TO STOP THIS EROSION OF OUR HEALTH CARE SYSTEM.

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PROPOSAL:

AGREE; I AM PLEASED WITH THIS DECISION, AS THIS WILL HAVE A GREAT IMPACT ON THE FUTURE OF ALL OF OUR CHILDREN, BROTHERS, SISTERS, ETC.

The authors state, “Based on large trials, primary screening using a clinically validated HPV test, such as HC2, appears very promising in women aged 35 years and older, particularly when coupled with reflex cytology to triage positive HPV results before colposcopy.”

AGREE.

REQUIRED TESTS ANNUALLY FOR ALL.

SCREENINGS: PREVENTATIVE CYTOLOGY: 3-5 YEARS IS FAIR.

After age 35, but perhaps for those at even higher risk, lower age to later 20s? Or offer 'exemptions' for special cases? While I believe Cytology to be perhaps the best; I just feel it is also imperative that young women have the knowledge of how it should affect childbearing in the future, etc.

so, yea!

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