Category Archives: Cervical Cancer & HPV

Cervical Cancer Screening Options: What Is Best For You?

Jared Hirschfield & Varuna Srinivasan, MBBS, MPH, National Center for Health Research


Smiling womenCervical cancer is cancer in the cells lining the cervix, the narrow passage between the uterus and vagina. This cancer is usually diagnosed in women between the ages of 35 and 44.1 Each year in the United States, approximately 13,000 women are diagnosed with cervical cancer and 4,700 women die from cervical cancer.1With regular screening and follow-up, however, cervical cancer is one of the easiest cancers to prevent and is highly curable if found early.

Almost all cases of cervical cancer are caused by the human papillomavirus (HPV), most commonly by two high-risk strains called HPV-16 and HPV-18.2 However, nine out of ten HPV infections go away on their own without treatment and do not result in cancer or any other health problems.

In addition to exposure to HPV-16 and HPV-18, there are other factors that put you at an increased risk for cervical cancer, including:3

  1.     Smoking
  2.     Multiple sexual partners and sexual intercourse at an early age
  3.     Obesity
  4.     In utero exposure to DES, a hormonal medication banned by the FDA in 1975
  5.     Long-term use of oral contraceptive pills
  6.     Multiple pregnancies
  7.     Other sexually transmitted diseases, such as HIV and chlamydia
  8.     Poor dietary habits or low consumption of fruits and vegetables
  9.     Family history of cervical cancer

Screening for cervical cancer

There are three screening methods to help detect and diagnose cervical cancer early when it is easy to treat. These include Pap smears, HPV tests, and a combination of both Pap smears and HPV tests (cotesting).

The United States Preventive Services Task Force (USPSTF) is a group of experts that recently updated its recommendations for cervical cancer screening.  They recommend no screening for women under 21 and a Pap smear every three years for women 21-29 years old. For women between the ages of 30 and 65, they recommend a Pap smear every 3 years or a high-risk HPV (hrHPV) test every 5 years.  As an “alternative,” USPSTF recommends Pap smear-HPV cotesting every 5 years. They do not recommend any screening for women over 65 or women who have had a hysterectomy.4

USPSTF Cervical Cancer Screening Recommendations (Updated August 2018)4

Women younger than 21 years
  • No screening of any kind
Women aged 21 to 29 years
  • Pap smear alone every 3 years
Women aged 30 to 65 years Preferred:

  • Pap smear alone every 3 years
  • hrHPV testing alone every 5 years

Alternative:

  • Pap smear-hrHPV cotesting every 5 years
Women older than 65 years
  • No screening of any kind
Women who have had a hysterectomy*
  • No screening of any kind

*with removal of the cervix

What is a Pap smear?

A Pap smear is used to evaluate abnormal cells in the cervix that can be diagnosed as pre-cancer or as cervical cancer. When a woman undergoes a Pap smear, a doctor or nurse collects cells from the outer layer of the cervix with a special stick, swab or a soft brush. The sample is then sent to a lab, where a pathologist checks for signs of abnormal cells. If the test is “positive,” the woman has abnormal cells, and those are graded, from least severe to most severe, as ASC-US (atypical squamous cells of undetermined significance), LSIL (low-grade squamous intraepithelial lesion), ASC-H (atypical squamous cells, cannot rule out HSIL), or HSIL (high-grade squamous intraepithelial lesion). Based on this grade, your doctor might recommend further testing, such as a colposcopy (a procedure in which the cervix is examined with a magnifying instrument) or a cervical biopsy.

What is an hrHPV test?

In a high-risk HPV test, also known as an hrHPV test, cells collected from the cervix are tested for the presence of HPV-16 and HPV-18, types of HPV that are most likely to cause cervical cancer. Keep in mind, however, that unlike the Pap smear, the HPV test does not tell you whether you have cervical cancer or are likely to develop cervical cancer.  Instead, it can only tell you if you currently have the virus that can be dangerous now or in the future.2

Which screening test is better?

The goal of both screening tests is to detect cervical cancer as early as possible while keeping the risks to women at a minimum. Pap smears and HPV testing accomplish this in different ways. Whereas Pap smears identify abnormal cells currently in your body, HPV testing indirectly measures your risk of precancer or cancer by identifying the presence of the virus.  HPV testing itself is not harmful, but testing for a virus that usually goes away by itself can lead to a very high rate of false positives.5 This means that people who may never actually develop cervical cancer may undergo expensive and painful invasive procedures to test for cancer and will experience the stress and fear of a cancer diagnosis.

Women with more than one sexual partner in recent years or whose sexual partner has other sexual partners are especially likely to have HPV. For that reason, the National Center for Health Research (NCHR) recommends a Pap smear every 3 years rather than an hrHPV test for these women. Alternatively, NCHR recommends combining a Pap smear and hrHPV test every 5 years.  In addition, we recommend that women over 65 who have recently had more than one sexual partner or have had a sexual partner who has had other sexual partners should continue regular Pap smears until age 75.

Bottom line: What is the best screening option for screening and how can cervical cancer be prevented?

The USPSTF recommendations are based on assumptions about the sexual activity of women at different ages. On average, women over 30 tend to have fewer sexual partners and more monogamous relationships than women under 30, and women over 65 have even fewer.  However, the National Center for Health Research recommendation is focused more on the number of sexual partners, and the fact that women in a monogamous relationship do not necessarily know if their sexual partner has had any other sexual partners. For that reason, we recommend Pap smears every 3 years or Pap smear-hrHPV cotesting every 5 years as the preferred methods of cervical cancer screening for most sexually active women aged 30 to 75. Pap smears directly determine the presence of cancerous or precancerous cells in your body. Cotesting can provide the added benefit of identifying high-risk HPV infection and allow for more vigilant follow-up if HPV-16 or HPV-18 is diagnosed.

In addition to monogamous relationships, women can reduce their chances of cervical cancer by using condoms. Other ways of reducing the risk include regular screening and follow-up with your physician, exercising, maintaining a healthy weight and balanced diet, and avoiding tobacco products.

 

[1] American Cancer Society. “Key Statistics for Cervical Cancer.” 04 January 2018. https://www.cancer.org/cancer/cervical-cancer/about/key-statistics.html.

[2] Centers for Disease Control. “Cervical Cancer.” December 2016. https://www.cdc.gov/cancer/cervical/pdf/cervical_facts.pdf.

[3] American Cancer Society, What Are the Risk Factors for Cervical Cancer?, www.cancer.org, https://www.cancer.org/cancer/cervical-cancer/causes-risks-prevention/risk-factors.html, October 3rd 2018

[4] US Preventive Services Task Force. “Screening for Cervical Cancer US Preventive Services Task Force Recommendation Statement.” JAMA2018;320(7):674–686. doi:10.1001/jama.2018.10897

[5] Rebolj, M. et al. “The Problem of False-Positive Human Papillomavirus DNA Tests in Cervical Screening.” Current Pharmaceutical Design(2013) 19: 1439. https://doi.org/10.2174/1381612811319080011

NCHR Comment on the USPSTF’s Draft Recommendations for Cervical Cancer Screening

2015

The National Center for Health Research is dedicated to improving the health and safety of adults and children by scrutinizing medical and scientific research. Based on our detailed analysis of currently available data, the Center strongly supports the existing USPSTF guidelines on cervical cancer screening which recommend Pap smears every 3 years starting at age 21, with the option of replacing that regimen starting at age 30 with a combination of a Pap smear and HPV test.

In response to the key systematic question regarding “the effectiveness of HPV testing, with or without cytology, as a primary screening strategy for reducing cancer mortality and incidence,” we strongly believe that this critical question must be divided into four questions: Is HPV testing effective with or without cytology (Pap smear) for women below 30 and for women above 30? Based on current data, the answers to those four questions seem to differ dramatically and more research will help answer those questions for different racial and ethnic groups.

Based on the research to date, HPV test without cytology should not be used as a screening tool. The HPV test by itself isn’t useful for women under 30 because many young women have HPV that will disappear without any treatment. Being objectively correct about whether HPV is present does not accurately predict whether infection with HPV will lead to cervical cancer.  On the contrary, the vast majority of women with HPV will never develop cervical cancer.   The only question is the extent to which HPV screening is useful for women over 30 and whether that is related to marital status or other measures associated with the number of sexual partners.

Positive results of an HPV test performed instead of a Pap smear, especially for women under 30, will add anxiety and lead to additional testing, as physicians follow a positive result on the HPV test with a colposcopy, an expensive and invasive procedure that could result in much lower compliance. Undergoing an HPV test without Pap smear is going to scare many women who are not at high or even moderate risk of cervical cancer.

The HPV test can only detect the presence of the virus, which in many cases will not result in cervical cancer; it cannot identify abnormal cells and it also cannot detect cancers of the cervix  that are not caused by HPV.

Although the FDA approved the use of the HPV test without cytology in 2014, it did not recommend replacing the safe and effective, well-established Pap screening regimen that has successfully prevented cervical cancer in the U.S.  FDA approval does not mean the HPV test is as good as the Pap smear, it only means it is better than placebo.

There has been little comparative effectiveness data comparing HPV-alone screening with HPV and cytology tests, known as co-testing. A new study published last month, conducted by scientists from the Quest Diagnostics laboratory and Magee-Women’s Hospital, analyzed data for over 256,000 women over 30[end Blatt AJ, Kennedy R, Luff RD, Austin RM, Rabin DS. Comparison of cervical cancer screening results among 256,648 women in multiple clinical practices. Cancer Cytopathol. 2015 May;123(5):282-8. Epub 2015 Apr 10.], and found that “approximately 19% of women with cervical cancer may be misdiagnosed by an HPV-only cervical screen.”  We urge the USPSTF to carefully review those data, and compare them to co-testing for women under 30 and those over 30.

The study data support co-testing in women ages 30 to 65 years as more effective at detecting pre-cancers and cancers. In addition, the study states that, “Co-testing performed better than HPV-alone or Pap-alone for cervical adenocarcinoma, a form of cervical cancer that is known to be harder to detect”.  It is important to consider and carefully scrutinize these data as the guidelines for cervical cancer screening undergo revision. We ask that USPSTF includes this study in its Proposed Research Approach — Evidence Review.

Current data indicate that HPV testing alone is likely to be much less accurate on women under 30, making the benefits of co-testing less likely for that age group.

In conclusion, based on current data and an excellent track record in the U.S., we believe Pap smear is an important screening tool, and that women should continue to rely on it every 3 years starting at age 21. Pap smears identify abnormalities in the cervix, which is useful by itself or together with an HPV test for women over 30. Most U.S. women who get cervical cancer did not have Pap smears within the last 5 years. In fact, some never had Pap smears. For that reason, women should continue to rely on Pap smears to screen for cervical cancer.  At the age of 30 or older, women may want to also be tested for HPV at the same time.

No more Pap smears?

By Diana Zuckerman, PhD
2014

If you’re a woman over 21, that headline probably got your attention. After all, who likes Pap smears? Wouldn’t it be great to never need one again?

Well, don’t get too excited because the alternative could be worse, if a Food and Drug Administration (FDA) advisory committee gets its way. The committee proposes replacing Pap smears with an equally invasive but less conclusive test, the HPV test, when women reach the age of 25. And then, if the HPV test indicates the presence of HPV (or human papillomavirus, which is very common in sexually active young women and usually goes away by itself), the committee proposes following up the test with an even more invasive procedure called a colposcopy. Patients describe a colposcopy as being like a Pap smear that takes 20 minutes instead of a few seconds.

The purpose of a Pap smear is to test for abnormal cells in your cervix that could eventually turn into cervical cancer. Two strains of HPV virus are responsible for 70 percent of cervical cancers. It’s very common for sexually active women to be infected with HPV, but usually the body gets rid of the virus within a year or two all on its own. HPV can only cause cancer when it lingers in the body for several years and starts to damage the cervix.

Even if a woman has had an HPV vaccine, she could still potentially develop cervical cancer, so experts advise women to get a Pap smear every three years, starting at age 21 and ending at age 65.  Starting at age 30, women are given the option of asking their doctor to use the same sample for a Pap smear and the test for HPV. If nothing suspicious is found, they can get screened using both tests every five years instead of every three for the Pap smear alone.

Current guidelines recommend that if a woman has an abnormal Pap smear and an HPV test indicating that she has the types of HPV that can cause cervical cancer, she should undergo a colposcopy to see if she needs surgery. Most women get Pap smears to screen for problems, and typically only get an HPV test if their Pap results indicate abnormal cells.

That’s why not many women currently get the HPV test. The company that makes HPV tests would like to sell more of them. So it’s asked the FDA to change the agency’s instructions for using the HPV test to screen healthy women. Instead of an optional use with Pap smears, it wants FDA approval to use the HPV test on its own to screen all healthy women starting at age 25.

Unfortunately, the HPV test by itself isn’t very useful because so many young women have HPV that will disappear without any treatment. Having an HPV test without also getting a Pap smear to check for problems is going to scare a lot of women who are not developing cervical cancer.  Instead of waiting a few months to see if the HPV goes away by itself (which it typically does), the company wants those women to get a colposcopy, which is as painful as a Pap smear but the pain lasts longer and the procedure costs more. And like a Pap smear, the test isn’t always accurate.

Otherwise, it’s a great idea.

We’re not the only ones who believe that the current guidelines should not be changed. The unbiased experts at the U.S. Preventive Services Task Force recommend that the HPV test only be used on women 30 and over, and only in combination with a Pap smear. They point out that if the HPV test is used on younger women, the results can’t distinguish between HPV that would go away on its own and HPV that could cause cancer. This would lead to unnecessary worry for young women and many unnecessary colposcopies.

At an FDA Advisory Committee meeting this month, Anna Mazzucco, PhD, from our staff expressed her concerns about replacing Pap smears with HPV tests. She pointed out that Pap smears provide inexpensive and and effective screening. In fact, the women who get cervical cancer are usually women who did not regularly get Pap smears or follow-up.

Research indicates that the way to save lives is to help women get screened with Pap smears, not to put them through unnecessary follow-up procedures. The American College of Gynecologists—the doctors who do Pap smears, HPV tests, and colposcopies—also expressed concerns about changing current policies, since there is no evidence that the proposed changes would save as many lives.

In addition, we believe that the more expensive and painful procedures would discourage women from getting screened or following up after receiving suspicious results.

What is going on at the FDA? Why are they choosing advisors who ignore the research evidence in favor of a new, unproven screening strategy? The FDA needs advisors who focus on scientific evidence and who make recommendations based on facts, rather than embracing every new “innovation” in health care, regardless of whether it will work.

When the “old ways” are effective, let’s not throw them out unless there is proof that the new, more expensive way is better.

 

A version of this post appeared in Huffington Post and Maria’s Country Kitchen.

Cervical Cancer Screening: The Key to Prevention

Padma Ravichandran, Danielle Pavliv and Brandel France de Bravo, MPH, Cancer Prevention and Treatment Fund

Cervical cancer and the Human Papilloma Virus (HPV)

The cervix is the lowest part of a woman’s uterus, connecting the uterus to the vagina. During childbirth, the baby leaves the uterus where he or she has been growing and squeezes past the cervix to pass through the vagina or birth canal.

Cancer of the cervix (cervical cancer) is the third most common form of cancer among women worldwide after breast cancer. In the initial stages of the disease, there often aren’t any symptoms, and the symptoms that do appear can be mistaken for other health conditions. These symptoms include: continuous vaginal discharge, vaginal bleeding between periods or after intercourse, vaginal bleeding after menopause, or heavier and longer periods. In the later stages of the cancer, a woman might have any of the following symptoms: weight loss, loss of appetite, fatigue, pelvic pain, back pain, leg pain, one swollen leg, heavy vaginal bleeding, urine or feces leaking from the vagina, or bone fractures.[1]

Almost all cervical cancer is caused by infection with the Human Papilloma Virus (HPV).[2] It is very easy to get infected with HPV because it spreads by skin to skin contact of the genitals or genital contact with mucous membranes (such as in the vagina, anus, or mouth). At least half of all sexually active men and women have been infected with HPV at some point in their lives.[3]

Although about 95 % of women diagnosed with cervical cancer show evidence of HPV infection, the vast majority of women who have been infected with HPV do not develop cervical cancer.[4] There are at least 40 strains of sexually transmitted HPV that affect the genitals, but HPV strains 16 and 18 cause approximately 70% of all cases of cervical cancer.[5]

Women exposed to HPV in their twenties or earlier are able to clear the virus more quickly than women exposed later in life. As women get older, it takes longer for their body to get rid of the infection, which increases their chance of developing cervical cancer.[6] Our bodies clear most HPV infections within 1-2 years, but the longer an infection lingers, especially strains 16 and 18, the more likely it will progress to pre-cancer. HPV can cause the cells of the cervix to grow abnormally, and abnormal cells can sometimes become pre-cancerous.[7]

Abnormal or precancerous cells often go away on their own (becoming normal cells again) without treatment. Since it is impossible to predict whether treatment is needed or not, the Pap smear test screens for abnormal and precancerous cells on the cervix.

About 6% of all Pap smears find abnormal cells or pre-cancers requiring follow-up, and those are surgically removed so that they won’t become cancerous.[8]

Cancers take years to develop, but cervical cancer tends to develop earlier in life than other cancers because HPV exposure often happens in late adolescence or early adulthood when people are most likely to have more than one sexual partner. Doctors have diagnosed precancerous growths or lesions on the cervix in women as young as 25 years old, but cervical cancer is usually diagnosed in women between the ages of 35-55.

Although HPV is the main cause of cervical cancer, smoking, having multiple births, and long-term use of oral contraceptives each increase the risk.[9]

Screening Tests

In order to identify any precancerous or cancerous cells before they become life-threatening, doctors encourage women to get routine Papanicolaou (Pap Smear) tests. Depending on a woman’s age, the doctor may also recommend one of the HPV tests.[10]

Pap Smear

The Pap smear, also known as cytology screening, is done in a doctor’s office, along with a pelvic exam. The gynecologist will take a sample of the cervical mucus and cervical cells and send them to the lab for testing. There, they look for abnormal cells or precancerous cells that might eventually become cancerous.[11] The Pap smear has long been used to screen for cervical cancer. In countries where this screening test is widely available, the number of cases of cervical cancer and the number of deaths from the disease have dropped dramatically.[12] In the United States, there has been a 70% reduction in cervical cancer incidence and mortality since the introduction of Pap smears.[13]

Researchers have found that women who have never gotten a Pap smear are three to ten times more likely to develop invasive cervical cancer than women who get routine screening.[14] Though precancerous cells can sometimes progress to cancer in as little as a year, that is rare and expert guidelines do not recommend annual screening for most women.

How Often Should You get a Pap Smear?

Not everyone agrees on when a woman should first get screened for cervical cancer and how often she should get screened. Recommendations given by different organizations over the years have varied. The one thing everyone seems to agree on is that there should be a minimum age and that beginning to screen too early is ineffective and even harmful. Young women often have abnormal cells on the cervix that the body can get rid of naturally. Positive Pap smear results, indicating the presence of abnormal cells, may lead a woman to undergo unnecessary treatment procedures that could cause emotional distress and physical discomfort.[15] Also, as a result of unnecessary treatment, these young women are more likely to have premature babies and babies with low-birth-weight.[16]

In 2012, the United States Preventive Services Task Force and a coalition consisting of the American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology released guidelines for screening for cervical cancer. [17,18] While the two sets of guidelines were created separately, they are consistent with one another. The chart below lists the newest recommendations for women as developed by these agencies and organizations. Cervical cancer screening guidelines are different if you have HIV/AIDS or have a suppressed immune system, if your mother took DES (diethylstilbestrol) when she was pregnant with you, or if you have already been told you have, or have been treated for, abnormal cells, precancerous cells, or cervical cancer.

Age group USPSTF and ACS/ASCCP/ASCP guidelines
Under 21 years Should not be screened regardless of the age of sexual initiation or other risk factors
21-29 years Recommends screening with cytology alone every 3 years
30-65 years Screening with cytology and HPV testing (known as “co-testing”) every 5 years is preferred, but cytology screening alone every 3 years is acceptable
Older than 65 years Women who have had negative screenings for the past 20 years and are not otherwise at high risk for cervical cancer should not be screened.*ACS/ASCCP/ASCP adds that screening should not be resumed for any reason, even if a woman reports a new sexual partner
After hysterectomy(surgery to remove the uterus) Women of any age who have had a hysterectomy   with removal of the cervix and who do not have a history of a high-grade precancerous lesion or cervical cancer should not be screened.

HPV Tests

The HPV test is done on the same sample of cervical cells and cervical mucus. When checking for abnormal or cancerous cells, the laboratory specialist can also check the cells for the HPV virus. There are two types of high risk HPV tests:  the Digene hc2 High Risk HPV Test and Cervista HPV HR test. The company that makes the Cervista HPV HR test recently developed a test that specifically looks for strains 16 and 18.

The Digene hc2 High Risk HPV Test has been around for some years and checks for thirteen high risk strains of HPV, including HPV 16 and 18. While this test can determine if a woman is infected with a high risk strain, it is not that effective at identifying which high risk HPV strain she has.[19] The second high risk HPV test, Cervista HPV HR is similar to the Digene hc2 High Risk HPV Test in that it screens for high risk strains of HPV. The difference between these two tests is that the Cervista HPV HR screens for fourteen strains compared to the thirteen that the Digene hc2 High Risk HPV Test screens for. Both tests are approved by the Food and Drug Administration (FDA) to screen for high risk strains of HPV in women over the age of 30. This means that the test is not approved for women under 30, even if they have an abnormal Pap smear. Women under 30 who are given this HPV test have a good chance of getting a false positive reading [20] (the test falsely says that she has HPV), which is why it is not approved for this age group.

The newest test, Cervista HPV 16/18, is a test that checks specifically for HPV 16 and 18, which are the strains responsible for most cases of cervical cancer. The drawback to this particular test is that it must be administered together with the Cervista HPV HR test.   Similar to the high risk HPV tests, the Cervista HPV 16/18 can only be administered on women above the age of 30. [21]

The HPV tests are helpful to physicians whose patients over 30 have had Pap smears with abnormal or precancerous cells. A woman who has precancerous cells and a positive HPV test is more likely to develop cervical cancer. The HPV test confirms that the woman has strains of HPV that could cause cancer. [22] The doctors are more likely to recommend immediate follow-up or treatment for these women than women with precancerous cells and no evidence of a high risk strain of HPV.

Women under 30 must rely exclusively on Pap smears once every three years for detecting and keeping a watchful eye on changes in cervical cells. The HPV test is of no use for women in this age group, because even if they are infected with one or more types of HPV most will be able to rid themselves of infection relatively quickly. If young women with abnormal Pap smears were given the HPV test, they would be likely to receive unnecessary treatment which could harm their reproductive system. [23]

The Bottom Line

Cervical cancer screening is simple, low-cost, and saves lives. Women should start getting Pap smears at 3-year intervals at age 21, and women over 30 whose Pap smear showed abnormal cells or pre-cancers may want to also get one of the HPV tests.

References:

  1. U.S. National Library of Medicine and National Institutes of Health. (2008). Cervical Cancer. Retrieved 18 February 2010, from the MedLine Plus Web Site:     http://www.nlm.nih.gov/medlineplus/ency/article/000893.htm
  2. zur Hausen, H. (2009). Papillomaviruses in the causation of human cancers-a brief historical account.  Virology, (384). 260-265.
  3. Center for Disease Control and Prevention. (2009). Genital HPV Infection-CDC Fact Sheet. Retrieved 9 February 2010 from the Center for Disease Control and Prevention Web Site: http://www.cdc.gov/STD/HPV/STDFact-HPV.htm
  4. National Cancer Institute. (2009). PDQ cancer information summaries: Cervical cancer. Retrieved 2 February 2010, from the National Cancer Institute Web Site:                 http://www.cancer.gov/cancertopics/pdq/screening/cervical/healthprofessional/allpages
  5. National Cancer Institute. (2008). Human papillomaviruses and cancer: Questions and answers. Retrieved 3 February 2010, from the National Cancer Institute Web Site:  http://www.cancer.gov/cancertopics/factsheet/Risk/HPV
  6. chiffman, M., Castle, P.E., Jeronimo, J., Rodriguez, A.C. & Wacholder, S. (2007). Human papillomavirus and cervical cancer. Lancet (370). 890-907.
  7. Schiffman, M., Castle, P.E., Jeronimo, J., Rodriguez, A.C. & Wacholder, S. (2007). Human papillomavirus and cervical cancer. Lancet (370). 890-907.
  8. National Cancer Insitute. Pap Test Fact Sheet. http://www.cancer.gov/cancertopics/factsheet/Detection/Pap-test . Retrieved 17 February, 2010.
  9. Schiffman, M., Castle, P.E., Jeronimo, J., Rodriguez, A.C. & Wacholder, S. (2007). Human papillomavirus and cervical cancer. Lancet (370). 890-907.
  10. Center for Disease Control and Prevention. (2009). Cervical cancer screening. Retrieved 1 Feb 2010  from the Center for Diseases Control and Prevention Web Site:   http://www.cdc.gov/cancer/cervical/basic_info/screening.htm
  11. Center for Disease Control and Prevention. (2009). Cervical cancer screening. Retrieved 1 Feb 2010, from the Center for Diseases Control and Prevention Web Site:   http://www.cdc.gov/cancer/cervical/basic_info/screening.htm
  12. National Cancer Institute. (2009). PDQ cancer information summaries: Cervical cancer. Retrieved 2 February 2010, from the National Cancer Institute Web Site:                 http://www.cancer.gov/cancertopics/pdq/screening/cervical/healthprofessional/allpages
  13. Baseman, J.G., Kulasingam, S.L., Harris, T.G., Hughes, J.P., Kivat, N.B., Mao, C., Koutsky, L.A. (2008). Evaluation of primary cervical cancer screening with an oncogenic human papillomavirus DNA test and cervical cytologic findings among women who attended family planning clinics in the United States. American Journal of Obstetrics and Gynecology(26). E1-E8.
  14. National Cancer Institute. (2009). PDQ cancer information summaries: Cervical cancer. Retrieved 2 February 2010, from the National Cancer Institute Web Site:                 http://www.cancer.gov/cancertopics/pdq/screening/cervical/healthprofessional/allpages
  15. National Cancer Institute. (2009). PDQ cancer information summaries: Cervical cancer. Retrieved 2 February 2010, from the National Cancer Institute Web Site:                 http://www.cancer.gov/cancertopics/pdq/screening/cervical/healthprofessional/allpages
  16. Samya, G.F. (2009). Cervical cancer screening-New guidelines and the balance between benefits and harms. New England Journal of Medicine (361). 2503-2505.
  17. Saslow D, Solomon D, Lawson HW, Killackey M, Kulasingam SL, Cain J,…Myers E. (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. American Journal of Clinical Pathology. (137).516-542.
  18. Whitlock EP, Vesco KK, Eder M, Lin JS, Senger CA, Burda BU. (2011). U.S. Preventive Services Task Force. Liquid -based cytology and human papillomavirus testing to screen for cervical cancer. Retrieved 4 June 2012 at: http://www.uspreventiveservicestaskforce.org/uspstf11/cervcancer/cervcancerupd.htm
  19. National Cancer Institute. (2009). PDQ cancer information summaries: Cervical cancer. Retrieved 2 February 2010, from the National Cancer Institute Web Site:                 http://www.cancer.gov/cancertopics/pdq/screening/cervical/healthprofessional/allpages
  20. Food and Drug Administration. (2003). Summary of safety and effectiveness data: Digene hybrid capture 2 high-risk HPV DNA test. Retrieved 8 Feb 2010, from the Food and Drug Administration Web Site: http://www.accessdata.fda.gov/cdrh_docs/pdf/P890064S009b.pdf
  21. Food and Drug Administration. (2009). Summary of safety and effectiveness data: Cervista HPV 16/18. Retrieved 8 February 2010, from the Food and Drug Administration Web Site:               http://www.accessdata.fda.gov/cdrh_docs/pdf8/P080015b.pdf
  22. Naucler, p. et al. (2009). Efficacy of HPV DNA testing with cytology triage and/or repeat HPV DNA  testing in primary cervical cancer screening. Journal of the National Cancer Institute (101). 88-99.
  23. National Cancer Institute. (2009). PDQ cancer information summaries: Cervical cancer. Retrieved 2 February 2010, from the National Cancer Institute Web Site: http://www.cancer.gov/cancertopics/pdq/screening/cervical/healthprofessional/allpages

Lowering the Cost of Cancer Treatment

Krista Brooks, Cancer Prevention and Treatment Fund

The number of new cases of the four most common types of cancers (prostate, breast, lung, and colorectal) have been declining since 1998, but Americans are still spending billions in cancer care costs.[1] In 2006, cancer care accounted for an estimated $104.1 billion in medical care spending in the United States and that number will continue to increase in the upcoming years.[1] The National Cancer Institute found that if incidence (which means the number of new cases), survival, and treatment costs stay the same, cancer costs in 2020 will show a 27% increase from 2010 solely based on the growing and aging population in the U.S.[2] As cancer treatment becomes more effective, the increasing number of cancer survivors will require additional care, which will also contribute to overall cost increases.[2] While these trends reflect a changing U.S. population and the increase in cancer survivors, they do not explain why each individual must pay so much for cancer care and treatment.

A survey conducted by the Kaiser Family Foundation found that one in four families affected by cancer say the experience used up all or most of the patient’s  savings, and one in eight say they borrowed money from relatives.[3] For the uninsured, the burden was even higher: “one in four delayed or decided not to get treatment because of its cost.”[3] These treatments are often essential, but the high costs are often not sustainable for individuals, families, or for the U.S. healthcare system.

Why do Cancer Treatment Costs Continue to Rise at Astronomical Rates?

Pharmaceutical companies, physician practices, and cancer screenings all play a role in the rising costs of treating cancer patients.  The treatment costs could be reduced, however.  Fortunately, there are now a variety of treatment options from which most patients can choose.  One problem is that pharmaceutical companies tend to charge higher prices for their new drugs; for example, Provenge, used to fight prostate cancer, is $93,000 for just one course of treatment.[4] Avastin typically costs stage 4 breast cancer patients more than $80,000, but the latest research indicates that for most patients it does not increase survival and is likely to harm quality of life.[5,6] Some cancer medications range from $5,000 to $10,000 per month, which over several years really adds up.[7] Many of these new drugs work for relatively few people, while most patients pay thousands of dollars and do not benefit or may even be harmed.  The companies have no incentive to determine which patients are most likely to benefit, if they can instead sell the drugs to most patients, including those who won’t benefit.  That leaves doctors and patients trying many expensive treatments until they find one that works for each individual.  Insurance companies, Medicare, and sometimes the individual must pay these exorbitant costs during this trial and error treatment.

Another factor that contributes to the high cost of cancer treatments can be a physician’s own treatment recommendations.  Physicians are there to help their patients, but research has shown that physicians who have financial ties to specific companies tend to recommend medical products made by those companies.[8,9] Many patients also rely on Medicare, which is not allowed to deny or limit cancer treatment based on cost.  As a result, Medicare patients and their doctors often have no incentive to choose equally effective but less expensive medications and treatments.[10,11] Doctors and patients also have little incentive to question high-priced treatments.[12] Unfortunately, physicians frequently do not adhere to evidence-based guidelines, leading them to sometimes prescribe and perform tests that may be more expensive than beneficial to patients.[13]

Cancer costs can add up-even before cancer is actually diagnosed.  Cancer screenings are designed to increase the number of patients who are diagnosed early, before they have any symptoms. When performed according to recommended guidelines, screening can help patients get a much earlier start on treatment. However, cancer screening tests often identify abnormalities that may or may not be cancer, which can result in expensive testing, unnecessary treatment, and added costs.  These costs can’t always be avoided, but they are increased when screening guidelines are not followed.  For example, a recent study found that a large number of elderly men were being screened for prostate cancer even though they were beyond the target age range for testing.[14] Prostate cancer screening tests can cause serious harm, exposing men to unnecessary treatments as well as unnecessary costs.  Similar results have been found for cervical cancer screening in women.  Certain types of HPV (Human Papillomavirus) have been linked to cervical cancer, so physicians like to determine the type of HPV as a method to screen for cervical cancer.  Unfortunately, a Center for Disease Control (CDC) study found that physicians are performing unnecessary and expensive routine HPV tests.[15] When HPV tests were initially developed, two types of tests were run together: one to detect HPVs that can cause cancer, and one for HPVs that don’t cause cancer.  However, now that an HPV test that focuses only on cancer-causing HPV has been available, that is the only HPV test recommended for physicians to use.  This recommended test should only be done for women over 21 who have inconclusive pap smear results, or women over 30 who are undergoing pap smears. The problem is that many physicians and clinics are using the cervical cancer HPV test routinely for all patients, or are using both the recommended HPV test and the non-recommended test for non-cancerous HPV; either of these inappropriate uses results in a doubling of medical bills, without any additional benefit to the patient.[16] Screening mammograms for women above or below the recommended age range, or given more frequently than recommended, also result in unnecessary anxiety, treatment, and medical expenses, which outweigh the benefits for most women.[17]

Is There Any Way to Reduce These Costs?

The skyrocketing cost of cancer treatments has brought the issue to public attention, as politicians, doctors, and organizations speak out about ways that we can work together to reduce these costs   Dr. Howard Brody’s “Call to Action” in the New England Journal of Medicine challenged physicians to name five high-priced treatments that are commonly used in practice, but have not been shown to be highly effective in patients.  He pointed out that if physicians can exchange these practices for low-cost, more effective treatments, a small dent could be made in rising healthcare costs.[18] Two oncologists responded to Brody’s request with five ways to reduce costs for cancer treatments.  They include using imaging and tests only where benefits to patients have been shown, limiting chemotherapy for people that are very weak and would not benefit from this additional treatment, and a greater coordination of care.  Additionally, they suggest an increased focus on palliative care, which has been found to make patients more comfortable, have better health outcomes, and reduce the number of costly and often ineffective treatments tried during the patient’s final months.[19,20]

To combat the rising costs of medications and medical devices, the 2010 health care reform law encourages more comparative effectiveness research through the formation of a non-profit Patient Centered Outcomes Research Institute.[21] This institute will help ensure that new medical treatments are studied to determine if they are better or worse than ones already on the market.  Similarly, two researchers are proposing a new type of regulation called “reference pricing” to ensure that patients are getting more out of these new treatments.  Reference pricing would require that medical products paid for by Medicare be tested to compare them to similar products that are already on the market. The companies would have 3 years to prove that their new product is better than the ones already on the market. If tests do not show that the product is safer or more effective, it could not be sold at a higher price than the older products on the market.  While reference pricing is not required as part of the health care reform law, it could be used as a strategy under the law to encourage medical product manufacturers to finance comparative effectiveness research.[22]

Changing physician and pharmaceutical company practices might seem like a daunting task, but there are some small steps that you as an individual can do to help lower costs associated with cancer treatments.  It is important that you discuss your financial and medical situation with your doctor. Make sure that you fully understand your illness and make sure your doctor fully understands your financial situation.  In some cases, your doctor may be able to prescribe less expensive, but just as effective, drug treatments that could save you money.[23] Additionally, it is important to talk to your doctor about regular cancer screenings and your family’s history of certain cancers or diseases.  You might be in the target age-range or at risk for other reasons that meet the standards of some screenings, but not for others.  This will help to maximize the benefits you will receive from these health screenings and help to eliminate unnecessary costs or treatments.[24]

Patients deserve a high standard of quality of care. Fortunately, it is possible to lower costs while maintaining or even improving the quality of care. We can do this with unbiased research to determine which treatments are most effective and by creating regulatory methods to ensure that the cost of medications must reflect their effectiveness.

If you or a loved one has been diagnosed with cancer and would like to learn about financial assistance options, please visit The National Cancer Institute (NCI) web site https://www.cancer.gov/about-cancer/managing-care/track-care-costs.  They offer a wide variety of resources to help with cancer treatment costs for those with and without health insurance.

References:

  1. National Cancer Institute, NIH, DHHS (2010) Cancer Trends Progress Report – 2009/2010 Update, Bethesda, MD, http://progressreport.cancer.gov.
  2. Mariotto AB, Yabroff KR, Shao Y, Feuer EJ, and Brown ML. (2011). Projections of the Cost of Cancer Care in the United States: 2010-2020., Journal of the National Cancer Institute 103(2). Retrieved from http://jnci.oxfordjournals.org/content/103/2/NP.2.full
  3. USA Today/Kaiser Family Foundation/Harvard School of Public Health National Survey of Households Affected by Cancer. November 20, 2009.http://www.kff.org/kaiserpolls/pomr112006pkg.cfm. Accessed February 10, 2010
  4.  No Author, (2011) The costly war on cancer. The Economist. Retrieved from http://www.economist.com/node/18743951
  5. Twombly, R. (2011). Avastin’s uncertain future in breast cancer treatment . Journal of the National Cancer Institute, 103(6), Retrieved from http://jnci.oxfordjournals.org/content/103/6/458.full
  6. Ranpura, V, Hapani, S, and Wu, S. (2011). Treatment-related mortality with bevacizumab in cancer patients. The Journal of the American Medical Association, 305(5), Retrieved from http://jama.ama-assn.org/content/305/5/487.full
  7. Goozner, M. (2011) Health care reform: Prove it works and CMS will pay. The Fiscal Times. Retrieved from http://www.thefiscaltimes.com/Articles/2010/10/05/Health-Care-Reform-CMS-Wants-Proof-to-Pay.aspx
  8. Elkin EB and Bach PB (2010). Cancer’s next frontier: Addressing high and increasing costs. The Journal of the American Medical Association, 303(24). Retrieved from http://jama.ama-assn.org/content/303/11/1086.short?home
  9. Jost, TS. (2010). Oversight of marketing relationships between physicians and the drug and device industry: a comparative study. American Journal of Law and Medicine, 36. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20726399
  10. Weight, CJ, Klien, EA, and Jones, JS. (2008). Androgen deprivation falls as orchiectomy rates rise after changes in reimbursement in the U.S. Medicare population. Cancer, 112(10), Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/18393326
  11. Goozner, M. (2011) Health care reform: Prove it works and CMS will pay. The Fiscal Times. Retrieved from http://www.thefiscaltimes.com/Articles/2010/10/05/Health-Care-Reform-CMS-Wants-Proof-to-Pay.aspx
  12. No Author, (2011) The costly war on cancer. The Economist. Retrieved from http://www.economist.com/node/18743951
  13. Brody, H. (2009). Medicine’s ethical responsibility for health care reform – the top five list. New England Journal of Medicine. Retrieved from http://healthpolicyandreform.nejm.org/?p=2616
  14. American Society of Clinical Oncology (2011). Many elderly men are undergoing unnecessary PSA screenings, researchers find. ScienceDaily. Retrieved June 20, 2011, from http://www.sciencedaily.com­/releases/2011/03/110328161848.htm
  15. Lee, JW, Berkowitz, Z, and Saraiya, M. (2011). Low-risk human papillomavirus testing and other nonrecommended human papillomavirus testing practices among U.S. health care providers. Obstetrics & Gynecology, 118(1), doi: 10.1097/AOG.0b013e3182210034
  16. Lee, JW, Berkowitz, Z, and Saraiya, M. (2011). Low-risk human papillomavirus testing and other nonrecommended human papillomavirus testing practices among U.S. health care providers. Obstetrics & Gynecology, 118(1), doi: 10.1097/AOG.0b013e3182210034
  17. Quanstrum, KH and Hayward, RA. (2010). Lessons from the mammography wars. New England Journal of Medicine, 363. Retrieved from http://www.nejm.org/doi/full/10.1056/NEJMsb1002538
  18. Brody, H. (2009). Medicine’s ethical responsibility for health care reform – the top five list. New England Journal of Medicine. Retrieved from http://healthpolicyandreform.nejm.org/?p=2616
  19. Mariotto AB, Yabroff KR, Shao Y, Feuer EJ, and Brown ML. (2011). Projections of the Cost of Cancer Care in the United States: 2010-2020., Journal of the National Cancer Institute 103(2). Retrieved from http://jnci.oxfordjournals.org/content/103/2/NP.2.full
  20. Smith TJ and Hillner BE. (2011). Bending the cost curve in cancer care. New England Journal of Medicine. Retrieved from http://healthpolicyandreform.nejm.org/?p=14541&query=home
  21. Kaiser Family Foundation. (2011, April 19). Summary of new health reform law. Retrieved from http://www.kff.org/healthreform/8061.cfm
  22. Goozner, M. (2011) Health care reform: Prove it works and CMS will pay. The Fiscal Times. Retrieved from http://www.thefiscaltimes.com/Articles/2010/10/05/Health-Care-Reform-CMS-Wants-Proof-to-Pay.aspx
  23. Consumers Union of U.S. (2009, March). 10 ways to reduce your drug costs. Retrieved from http://www.consumerreports.org/health/prescription-drugs/10-ways-to-reduce-your-drug-costs/overview/10-ways-to-reduce-your-drug-costs.htm
  24. Quanstrum, KH, and Hayward, RA. (2010). Lessons from the mammography wars. New England Journal of Medicine, 363. Retrieved from http://www.nejm.org/doi/full/10.1056/NEJMsb1002538

A Closer Look at HPV and the HPV Vaccine

Megan Cole, Diana Zuckerman, PhD, Brandel France de Bravo, MPH, and Janet A. Phoenix, MD, Cancer Prevention and Treatment Fund

What is HPV?

The human papillomavirus virus, also known as HPV, is the most common sexually transmitted infection-both in the U.S. and around the world. In fact, approximately 20 million Americans are currently infected with HPV, and another 6 million become newly infected every year.[1] By age 50, 70-80% of all women will have contracted at least one strain of HPV. The virus is transmitted through skin-to-skin contact and is usually sexually transmitted-vaginally, anally, or sometimes, orally. However, many of the HPV types can be transmitted through non-sexual contact as well.

This virus may lead to several types of cancers in women, including cancers of the cervix, vulva, vagina, and anus. However, a person is much more likely to get cervical cancer than the other three cancers combined. There are approximately 130 strains of HPV, some of which may cause warts and others which may cause cancer. Of these strains, two types cause 70% of cervical cancer cases (strains 16 and 18) and two types cause 90% of genital warts cases (strains 6 and 11).[1] Most HPV infections in adolescents are short term-70% of infections disappear within a year and 90% disappear within two years. However, while most HPV infections go away on their own, it is possible for abnormal cells to develop on the cervix, vulva, vagina or anus when high-risk types of HPV persist over time. If those high-risk abnormal cells (CIN 2, CIN 3 or HSIL, which stands for “high-grade squamous intraepithelial lesions”) are not detected and treated, they can eventually cause cancer.[2]

It takes about 15-20 years for this to happen, and meanwhile, the women are unlikely to have symptoms. That’s why HPV can go undetected and cause cancer, especially for those without access to regular Pap smears or other medical care.[3]

Although HPV and cervical cancer are a concern for all women, in the U.S., the women with the highest rates of cervical cancer are minority and low-income women. While far fewer women die of cervical cancer in the U.S. compared to many other countries, it is still a deadly disease for thousands of women every year.  African-American women are twice as likely to die from cervical cancer as white women. One study found that cervical cancer rates for whites were 9.2 per 100,000, compared to 12.4 for African Americans and 16.8 for Hispanics. The same study reported death rates of 2.7 per 100,000 for whites, compared to 5.9 for African Americans and 3.7 for Hispanics.[4]

When women die of cervical cancer, it is usually because they have not had a Pap smear in many years, if ever, and their cancer is caught very late. Pap smears detect cervical cell changes early on, helping to save lives. In fact, having a regular screening every 2 to 3 years greatly reduces a woman’s risk of getting cervical cancer. The widespread use of the Pap test has reduced cervical cancer in the U.S. by more than half over the past 30 years.[5]

Poverty is a risk factor as well: a 2007 study showed that 23% of women living below the poverty line tested positive for high-risk HPV (strains 16 and 18), while only 12% of women living at least three times above the poverty line tested positive for high-risk HPV.[6] This is probably due to lower-income women having fewer Pap smears.

To reduce your risk of death from HPV causing cervical cancer, the best strategies are:

1.  Get regular Pap smears. They detect changes in the cervix caused by HPV.

2.  Use condoms. They reduce your chances of getting infected with HPV but they don’t eliminate your risk, because skin-to-skin contact still occurs when a condom is used.

3.  Limit your number of sex partners.

4.  Get an HPV vaccine. HPV vaccines help protect against the most common types of HPV. The first HPV vaccine became available in 2006.

The HPV Vaccine

Gardasil was approved by the Food and Drug Administration (FDA) in June 2006 and received a lot of publicity as “the first cancer vaccine.” Gardasil is approved to protect girls and women, ages 9 through 26, from the two types of HPV infection that are responsible for 70% of cervical cancer cases and two other types of HPV infection that are responsible for 90% of genital warts cases. It has very limited effectiveness, however, against other types of HPV that cause approximately 30% of cervical cancers. For that reason, girls and women who are vaccinated with Gardasil will still need regular Pap smears to detect cervical cancer in its early stages when treatment is most effective. In 2008, Gardasil was also approved to protect against vaginal and vulvar cancers.[7]

The Gardasil vaccine is administered in three doses over a six-month period. The vaccine data so far are short-term, and vaccine producer Merck states very clearly on the home page of its Gardasil website (www.Gardasil.com) that: “The duration of protection of Gardasil has not been established.”

Several clinical trials have been conducted, but most for under five years and none for 10 years or longer.  We still cannot be certain whether Gardasil will be effective for all women for 5 years, nor do we know what percentage of women will be protected for longer than 5 years. Because cancers take so long to develop, we will not know the true impact of Gardasil on cervical cancer for several decades. It is important to know if Gardasil will require a booster shot in order for it to offer long-term protection, but those studies have not yet been conducted.

A second HPV vaccine, known as Cervarix, was approved by the FDA in October 2009. It is produced by GlaxoSmithKline and became available in May 2010. Cervarix was approved for use in girls ages 10 to 25, and like Gardasil, is given as a three dose series over six months. Cervarix costs about the same as Gardasil: on average, $385 for the three doses of the vaccine. Unlike Gardasil, Cervarix only protects against two HPV strains-types 16 and 18, which are the leading causes of cervical cancer. Like Gardasil, the long-term effectiveness is still unknown and the need for a booster shot to maintain protection is uncertain.

What’s the Difference Between the Two Vaccines? Are They Both Safe?

While no head-to-head studies have been done comparing the overall effectiveness of Cervarix and Gardasil, we do know about some differences. In clinical trials, Cervarix was shown to be 93% effective in preventing cervical pre-cancers associated with HPV 16 or HPV 18 in women-this means that it protects against abnormal cervical changes that could lead to cervical cancer. It may also provide protection against other strains of HPV, including types 45 and 31, which also cause cervical cancers. In clinical trials, Cervarix was 75% effective at protecting against three cancer-causing types of HPV that are not part of the vaccine, while Gardasil is only 50% effective at protecting against other cancer-causing HPV types.

As with any vaccine, it is important to consider the vaccine’s safety and potential side effects. The safety of the HPV vaccine was studied in clinical trials before it was licensed. For Gardasil, over 29,000 males and females participated in the trials, while Cervarix studied over 30,000 females from around the world.

In addition to clinical trials, safety information is available through the Vaccine Adverse Event Reporting System (VAERS).  As of September 30, 2010, of the 32 million doses of Gardarsil that have been distributed in the U.S., 17,160 adverse events have been reported. Of these reports, 92% were considered non-serious, which includes fainting, pain and swelling at the injection site, headache, nausea, and fever. It should be noted that fainting is common following most injections and vaccinations. In addition, 8% of the reported events were considered serious. All of these serious reports have been carefully reviewed by medical experts and no common medical problems caused by the vaccine were found. However, there have been some reports of individuals getting blood clots after receiving the vaccine, although these individuals had other blood clot risk factors such as using birth control pills, smoking, and obesity. As of September 30, 2010, there have been 56 U.S. reports of death among females who have received the Gardasil vaccine, with 30 of the reports confirmed. Of the confirmed reports, there was no unusual pattern to suggest that the deaths were caused by the vaccine.[8]

In spite of this finding, there has been some concern about a link between Gardasil and a rare nervous system disorder known as Guillain-Barré syndrome (GBS). In a 2010 study in Vaccine, Nizar Souayah and co-authors looked at the VAERS database between June 2006 and September 2009 and compared the occurrence of Guillain-Barré syndrome after vaccination with Gardasil to the occurrence after vaccination with Menactra and influenza.[9] The researchers concluded that the average weekly reporting rate of GBS for the six weeks after vaccination was 6.6 events per week per 10 million subjects, which is double what it was for Menactra (also administered to children 11 and up), and about five times the weekly reporting rate for flu vaccine. When limited to the first two weeks after vaccination, the average weekly reporting rate of GBS jumped to 14.5 cases per week per 10 million subjects vaccinated with Gardasil as compared to 5.7 cases among subjects vaccinated with Menactra.

Three CDC researchers have criticized Souayah’s study, pointing out that the VAERS database has numerous shortcomings and that the authors used as their denominator the number of doses distributed, divided by 3, even though not everyone receives all three doses. They also maintain that being a new vaccine, adverse reactions to Gardasil were over-reported.

There are, in fact, problems with VAERS-it is a passive system-but usually the problem is under-reporting. Most parents don’t know how to report problems or don’t find the time to do so, and many doctors under-report as well. If there was extensive under-reporting of problems associated with Gardasil, then that may have partly offset Sourayah’s overestimation of the number of people getting all 3 doses. Clearly, more research will need to be done to determine if Gardasil slightly increases the very low risk of GBS.

Cervarix has only been linked to 3 adverse event reports so far. This low number is due to the fact that the vaccine was only recently approved in the U.S., and relatively few individuals have received it so far.

National Recommendations

On June 29, 2006, the CDC Advisory Committee on Immunization Practices (ACIP) recommended that Gardasil be given routinely to all 11-12 year old girls. The recommendation was based on less than two years of efficacy, safety and immunogenicity data provided to the FDA from clinical trials with 16-23 year-olds, combined with safety and immunity studies in 9-15 year old girls.[10] In October of 2009, the CDC’s ACIP also recommended Cervarix for 11-12 year old girls, but this too was based on short-term data. However, Cervarix’s approval was based on several studies where subjects were followed for an average of 3 to 7.5 years-a longer period than the Gardasil studies, but still not long enough to know the longer-term effects of the vaccine.

If the goal is to prevent cervical cancer in females, either Cervarix or Gardasil may be used, said the committee, which further noted that one vaccine could be substituted for the other, if needed, to complete the three-dose series.

Who should get it? Who should not?

The data that Merck presented to the FDA in 2006 indicated that Gardasil would not be effective against strains of HPV that the women were currently infected with at the time of vaccination. This finding has often been misunderstood. What it means is that the vaccine will not treat existing infections. However, data show that having a previous HPV infection that has cleared by the time you get the vaccine will not interfere with the vaccine’s effectiveness. But, if you have an ACTIVE infection that has not cleared, the vaccine will not be as effective against that type of HPV in the future.

At what Age is it Most Effective?

Because HPV exposure may occur even in the first 10 years of life through non-sexual skin-to-skin contact, or while being born, there is no age at which the vaccine will always be effective for everyone. According to the Centers for Disease Control (CDC), “the best way a person can be sure to get the most benefit from HPV vaccination is to complete all three doses before beginning sexual activity.”[11] While researchers still do not understand or agree on the level of antibody titers necessary to have protection from HPV, there are data to indicate that most teenagers and women who are vaccinated after being previously exposed to HPV have even more antibodies than those who are vaccinated before they become sexually active.[12]

So, is it a good idea to vaccinate girls as young as 12? It is difficult to answer that question because we don’t know how long the vaccines last. A few years from now, the vaccine manufacturers may announce that booster shots are needed. If that’s the case, will young adults who were vaccinated as children actually get them?  What if the booster is expensive and they don’t have coverage for it?

In spite of these unknowns, several states are considering laws requiring HPV vaccines for school attendance. In Virginia and Washington, D.C., for example, all girls entering sixth grade in the fall of 2009 were required to be vaccinated against HPV unless a parent specifically requested a waiver. While the vaccine may be safe for girls as young as 12, we do not yet have enough data on how effective it is or how long it lasts to justify this policy, particularly given the high cost of the vaccine to working class and middle class parents and to government health programs for the poor. The vaccine’s safety and antibody response was tested on girls as young as 9 and 10, but the impact on lesions or disease was not studied in girls under 16. Since data show that the antibodies protecting vaccinated girls and women against HPV 18, a major cause of cervical cancer, appear to decrease over time, many girls vaccinated at age 12 could possibly lose much of their immunity against HPV 18 just as they are becoming more sexually active at ages 16 or 17.

As with any sexually transmitted disease, all it takes is exposure to one infected partner to acquire HPV. The chances of HPV and cervical cancer increase with the number of sexual partners, and the number of sexual partners of their sexual partners. Research is now underway to evaluate the effectiveness of Gardasil among women 27 to 45, and also in boys and men.

To view statements and testimony on NCHR’s opinions and recommendations for the HPV vaccine, visit http://www.center4research.org/2009/04/testimony-of-dr-diana-zuckerman-before-dc-health-committee-on-hpv/ or http://dev.stopcancerfund.org/p-cervical-cancer-hpv/hpv-q-a/

How Do I Get an HPV Vaccine?

The retail price of the vaccine is about $125 per dose (or $375 for full series), but most large insurers cover the costs of the vaccine, which may be administered by your doctor.

It is estimated that 85-89% of children with health insurance are covered for the HPV vaccine and other routine vaccinations.[13,14,15] The CDC Committee has also recommended that the HPV vaccine be included in the Vaccines for Children (VFC) Program, the federal program which provides free vaccinations to children 18 years of age and under who are uninsured, on Medicaid, protected by the Indian Health Services Act, or underinsured.[15] Children enrolled in the VFC program receive the vaccine free of charge. Approximately 41% of all childhood vaccines in the United States are purchased by and administered through the VFC Program.[16] However, the CDC recommendation does not include a booster shot, and even if it did, once girls are older than 18 years, the VFC Program would not cover the cost of the HPV vaccine or a booster.

Additional details regarding the Vaccines for Children Program, including what it is, who is eligible, what it covers, and how to enroll, may be found at http://www.center4research.org/vaccines-children-program-vfc/

The Great Debate: Is it Worth it?

There are certainly both benefits and drawbacks for the HPV vaccine, with some people benefiting more than others. From a broad perspective, the vaccine may not be cost effective because long-term effectiveness is unknown and we don’t yet know if booster shots are necessary to sustain protection against the virus. According to a modeling analysis done by Ruanne Barnabas, a cervical cancer vaccine must last at least 15 years in order to prevent cancer and not just postpone it.[18]

Getting regular Pap smears and screenings and limiting your number of sexual partners are effective strategies whether you are vaccinated or not, so spending money on Pap smears may be the most economical way to protect women against HPV and cervical cancer. However, for women who are less likely to undergo regular Pap smears, and especially for women at highest risk for getting HPV and cervical cancer (such as Hispanics and blacks), the HPV vaccine reduces risk.

Who’s Getting Vaccinated?

According to the CDC, in the general U.S. population of adolescents 13 to 17 years old, 37% have received at least one dose of the three-dose vaccination and 18% have received all three doses of the vaccination, as of 2008. Given that the vaccination was relatively new at the time of data collection, it’s safe to assume that these rates have increased over the past two years.[17] Also, as of 2008, 42% of adolescents living at or above poverty received at least one dose of the vaccine, with 36% receiving all three doses. In comparison, for those living below poverty, 41% have received at least one dose of the vaccine, while 46% have received all three doses of the vaccine. Girls and women living below poverty were fully vaccinated at a higher rate than those living at or above poverty. When looking at coverage by race/ethnicity, 35% of white adolescents have been covered by the vaccine, in comparison to 36% of blacks, 44% of Hispanics, 53% of American Indian/Alaska Natives, and 41% of Asians.[16] High rates of coverage among those at or below poverty level, and among American Indian/Alaska Natives, can be partly explained by the VFC program (see our article “The Vaccines for Children Program (VFC)”).

Effect of Vaccine and VFC on Racial and Social Differences in HPV and Cervical Cancer Rates

Because the HPV vaccination is provided under VFC, this may eventually reduce differences in HPV and cervical cancer rates by protecting the most at-risk individuals against the four primary HPV types. When looking at racial statistics about who is getting the vaccine, Hispanics and American Indians/Alaska Natives are receiving the vaccine at much higher rates than whites and blacks. Because Hispanics have higher rates of cervical cancer in comparison to whites and blacks, the VCF Program could narrow this gap.  The VFC Program can reach out to the medically underserved, who are less likely to receive regular cancer-prevention screenings. Assuming that the vaccine is effective in the long-run (which is still unknown), the VFC program could potentially prevent 70% of HPV cases in those who are vaccinated. As a result, expensive follow-ups to abnormal pap smears may also be avoided. However, even with the vaccine, it is still very important to get regular pap smears to stay healthy and prevent cervical cancer.

The Bottom Line

Like any public health strategy, a vaccine’s risks must be weighed against its benefits. That is why it is so important to determine how effective the vaccine is against preventing HPV and cervical cancer, and for how long. If the vaccine is offering less protection than it promises or is wearing off by the time most girls are becoming sexually active, then some people may decide that the cost and risks of the vaccine simply aren’t worth it. It’s important to remember that whatever you decide, you still need to get regular Pap smears. But for women who can’t or don’t get annual Pap smears and who can get the HPV vaccine at low or no cost through their insurance or through the VFC Program, the HPV vaccines (Gardasil or Cervarix) provide needed protection.

References:

  1. Centers for Disease Control and Prevention (CDC) (2009) Genital HPV Infection Fact Sheet. Retrieved from http://www.cdc.gov/STD/HPV/STDFact-HPV.htm.
  2. Cullins M. (2009) HPV: Planned Parenthood. Retrieved from http://www.plannedparenthood.org/health-topics/stds-hiv-safer-sex/hpv-4272.htm.
  3. Schiffman M and Castle PE (2003 Aug.) Human papillomavirus: epidemiology and public health. Archives of Pathology and Laboratory Medicine 127(8):930-934. Retrieved from (PMID 12873163) http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=127&page=930.
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HPV: Q & A

Brandel France de Bravo, MPH, Maushami DeSoto, Ph.D., and Krystle Seu, Cancer Prevention and Treatment Fund

Q: What do I need to know about HPV?

A: Human Papilloma Virus (HPV) is the name for a group of viruses that cause cervical cancer, genital warts and several other diseases. There are more than 120 different types of HPV. Many of them are spread through sexual contact and affect the genital areas of men and women. Although most types of HPV do not increase the risk of cancer, some types spread through sexual contact can cause cancers in male or female genitals, the anus, or the throat area. In fact, two types-HPV 16 and HPV 18-are responsible for approximately 70% of all cases of cervical cancer. You should also know that HPV infections are usually asymptomatic, meaning people who are infected don’t even realize they have the virus. Most of the time HPV infections clear up by themselves the same way a person with a cold virus gets better with time. Nine out of ten people are “over” their HPV, regardless of the type, in less than two years.

Q: What is this HPV vaccine, Gardasil?

A: Gardasil is the first vaccine ever sold in the U.S. to prevent cancer: cervical cancer. It was approved by the FDA in June 2006 for use among girls and women between the ages of 9 and 26. It helps protect them from 4 of the more than 120 types of HPV. It provides protection against HPV 6 and HPV 11, which cause 90% of genital warts, and against HPV 16 and HPV 18, which are responsible for 70% of cervical cancer cases. In addition to protecting girls and women who were never before exposed to HPV, it can also protect a sexually active girl or woman who was previously exposed to HPV from getting re-infected. If a girl or woman is actively infected with HPV at the time of vaccination, however, the vaccine would not protect her against cervical cancer. The vaccine does not protect against most of the other types of HPV that cause 30% of cervical cancers, and it can’t be used to “cure” or treat an active HPV infection. This is why it’s so important that women who are sexually active get regular PAP smears (every 3 years) starting at age 21. Pap smears are able to detect cervical cancer in its early stages when treatment is most effective.

Q: How long does the vaccine’s protection last?

A: According to Gardasil’s Web site (www.gardasil.com), it has not been established exactly how long the vaccine’s protection lasts. Gardasil is still very new, and because cancers can take years to develop it will be many years before we know conclusively how effective the vaccine is in providing lifelong protection against cervical cancer. However, studies of antibodies of vaccinated girls and women have shown that the vaccine’s protection against HPV 18-one of the two types of HPV that cause cervical cancer-may wear off for many girls and women in as little as 3 years. Uncertainty about the duration of the vaccine’s protection on top of the high cost (about $400-$1,000 for all three doses) should make you think twice about rushing out to get it.

Q: You’re saying that the protection may not last more than a few years. Is there a booster shot to make it last longer?

A: The manufacturer of Gardasil, Merck, has not publicly stated that a booster shot is needed, but in their key study for the FDA, the company gave a booster shot to all the girls and women after 60 months (5 years)-just a week before they tested their antibodies and concluded that the vaccine provided protection after 5 years! Even in the study, Merck didn’t call this additional shot a booster shot, but rather a “challenge dose”-as if they were trying to confuse anyone reading the study results. And it worked. Most health officials are not aware that the vaccine apparently requires a booster.

Even worse, the company did not compare women who got this extra (booster) dose to those who didn’t. As a result, nobody knows how long the vaccine lasts without a booster. And the company has not published any research to show how long the booster lasts either. Is it one year, 3 years, 5 years, 10 years? There is no public information about it.

Q: How much does the vaccine cost?

A: Gardasil is the most expensive vaccine to have ever been recommended for school-age children. The vaccine manufacturer charges $120 for each dose (not counting the doctor’s fee), and the total cost per patient for the initial 3-shot regimen ranges from $400-$1,000. If the HPV vaccine is mandated in your state and you can not afford to pay for it, the cost will be covered by the Federal Government which provides the vaccine to clinics and health providers that participate in the Vaccines for Children program. The high cost of the vaccine and the unknowns about the cost and frequency of booster shots raise serious concerns about mandating the vaccine for 12 year olds.

Q: What’s the best age to get vaccinated with Gardasil?

A: Because the vaccine’s protection against HPV 18 can wear off in as little as three years, a girl vaccinated at 12 could lose her protection against cervical cancer just when she is most likely to become sexually active-at 15 or 16.

Health officials have recommended that girls get vaccinated at age 12 based on Merck’s conclusion that Gardasil is not effective against current (active) HPV infections, and therefore is most effective for girls who are not yet sexually active. But the company’s own research shows that the vaccine is as effective or more effective among girls and women with previous (not active) HPV infections as among young girls who have never been exposed to HPV through sex. This is good news because older girls and women with past exposure to HPV are clearly sexually active and therefore are more in need of the protection that Gardasil provides. New research from France also supports this: a French researcher recently presented results of a study on 17,000 women and found that Gardasil prevented cervical lesions among women with previous HPV exposure at nearly the same rate as it did among women with no previous HPV exposure.

This new research means that the only girls or women who would not benefit from Gardasil are those that have current, active infections at the time that they are vaccinated. From a cost-effectiveness point of view, even if the vaccine is effective for a few years, it is probably better to wait until a girl or women is sexually active before vaccinating her, instead of vaccinating 12-year olds. But, unless a booster lasts a very long time, it will be very expensive to keep getting vaccinated, no matter how old a girl or woman is when she is first vaccinated.

Q: What are the side effects and risks of Gardasil?

A: As of August 2008, more than 20 million doses of Gardasil had been distributed in the U.S. and there were 10,326 reports registered through the CDC’s Vaccine Adverse Event Reporting System (VAERS). Minor side effects, such as pain or tenderness at the injection site, are quite common. The most common side-effect observed since Gardasil became available to the public is fainting after receiving the vaccine, which is being dealt with by warning health providers to keep patients under observation for 15 minutes after giving the shot.

Serious but rare side effects such as Guillain-Barré Syndrome (GBS), which causes muscle weakness, have been reported. According to the CDC, cases of GBS following administration of Gardasil do not represent a statistically significant increased risk, even though 9 of the 13 reported cases of GBS occurred during a biologically plausible time frame, meaning that the vaccine could plausibly be the cause. A few girls who were vaccinated with Gardasil have died, but it is not known if the vaccine is the cause.

More research is needed to determine if girls or women vaccinated with Gardasil are at an increased risk for GBS or other serious side effects.

Like any medical product, a vaccine’s risks must be weighed against its benefits. This is why it is so important to determine how long the vaccine lasts and how well it works. Since the vaccine is so expensive, if it provides only a few years protection, almost any risk becomes unacceptable.

Q: Does anyone else make a more effective or less expensive HPV vaccine?

A: Cervarix, made by Glaxo Smith Kline, has been approved for use in at least 66 countries in Europe and Australia. It is not yet approved for use in this country because the Food and Drug Administration (FDA) asked for longer-term studies of Cervarix than it required of Gardasil. Published studies suggest that Cervarix may provide protection against the two viruses that cause most cervical cancer (HPV 18 and 16) for at least 6.4 years. The FDA will not approve Cervarix until the necessary studies are completed, and we won’t know much about the studies until FDA reviews them. Comparisons of the two vaccines would enable policy makers to make better-informed decisions, and the availability of a second, competing HPV vaccine might help make vaccinating against HPV more affordable.

Q: What are other ways of preventing HPV?

A: Cervical cancer can be prevented with routine cervical cancer screening (Pap smears) and follow-up of abnormal results. The Pap test can identify abnormal or pre-cancerous changes in the cervix so that they can be removed before cancer develops. Even if you have been vaccinated with Gardasil, you have to get regular Pap screening because the vaccine doesn’t protect against all the types of HPV that can cause cervical cancer.

HPV is spread by skin to skin contact. Sexual intercourse is not necessary. The more people who you have been sexually active with, the more likely you are to get an HPV infection. This also applies to the number of sexual partners your partner may have had. When sexually active, using a condom correctly can greatly reduce the chances of being exposed to HPV as well as other sexually transmitted illnesses and viruses. But sex with just one person or even contact that you wouldn’t think of as sexual can be enough to spread HPV. According to the Centers for Disease Control, about 10% of all children have been exposed to HPV 16, the most cancerous of the HPV types, in their first ten years of life. This sounds scary but remember that 90% of cases of HPV clear up all by themselves-without any long-lasting effects-in two years or less.

Q: Should boys get Gardasil?

A: Merck is asking the FDA to approve Gardasil for boys and men, because it can prevent genital warts. It can also prevent anal and throat cancers, but those cancers are rare (although more common among gay men than heterosexual men).However, until we know how long Gardasil can protect against the viruses causing cancer or genital warts, and until we know more about the risks of side effects, it is impossible to know if the benefits outweigh the risks for boys and men.