Making Strides Against Cervical Cancer While Reducing Burden - HPV Vaccination and HPV Testing

By Sydney Philpott

Human papillomavirus (HPV) is a very common sexually transmitted infection. According to the World Health Organization (WHO), most sexually active women and men will have an HPV infection at some point in their lives. While HPV infections usually go away on their own, certain types persist and then serve as the primary cause of cervical cancer. Globally, HPV leads to about 600,000 new cases of cervical and genitourinary cancer each year, with about 26,900 cases in the United States alone.

In 2006, HPV vaccination became available worldwide and was recommended by the WHO and the Centers for Disease Control and Prevention (CDC) for girls age 9-26 and recommended for boys of the same age group in 2011. After just 5-6 years, studies in the United States found that HPV infections in girls age 14-19 dropped 64 percent, risk of cervical pre-cancer was lowered by 47 percent, and there was a 61 percent reduction in treatment for genital warts (infographic). The WHO estimates that two-thirds of new cases of cervical cancer could be prevented if 80 percent of those age-eligible were vaccinated worldwide.

Despite these improvements, vaccination rates in the United States have remained low. On average, only 60 percent of girls age 13-17 initiate the HPV vaccination series and 39.7 percent receive all three recommended doses, while only 41.7 percent of boys initiate and 21.6 percent complete the series. Additionally, there are clear racial and socioeconomic disparities for vaccination in the United States – but these often move in a direction opposite from many health behaviors. Among adolescent girls age 13-17 in 2014, 66 percent of blacks and Hispanics had at least one dose of the HPV vaccine, while 56 percent of whites did. Similarly, 67 percent of those below the poverty line started the series, while only 58 percent above did.

These numbers, though, change a bit when looking at the percentage of girls completing the full three-dose series once they start it, suggesting that efforts that drive initiation of the vaccine fall off in certain groups when it comes to completing the entire series. Of girls who started the series, 68 percent of those living below the poverty level and 69 percent of those living above went on to complete the 3 doses – nearly identical numbers. Similarly, over 70 percent of Hispanics and whites completed the series once they started, whereas only 62 percent of blacks did.

While the relatively high vaccination initiation rate in African Americans is heartening, it's also important to ensure that as many girls as possible get subsequent doses so they are as protected as possible in the future. Currently, African American women are more likely to be diagnosed with cervical cancer at later disease stages and die at almost twice the rate compared with non-Hispanic white women. Improving rates of HPV vaccination and completion across all groups can help narrow such cancer disparities.

Furthermore, recent systematic reviews examining efforts to increase HPV vaccination use in the U.S. have conflicting conclusions, and the relative success of these interventions fell short of national averages and stated vaccination goals.

Compared to the United States, other countries have had considerably more success achieving high HPV vaccination rates. Through implementation of school-based vaccination programs, Scotland reported 81 percent three-dose vaccination in 2011, England reported 76 percent in 2010 and Australia 73 percent in 2014. In 2013, the United States reported that only 37.6 percent of adolescent girls age 13-17 had all three vaccine doses.

These discrepancies may be due to the three-dose requirement remaining a substantial barrier to successful HPV vaccination in the United States. However, recent evidence indicates that fewer than three doses may be protective. Brotherton et al. found that less than three doses provides some protection against cervical disease in Australian women, even when measured within 5 years in a population including those who were sexually active at the time of vaccination. Therefore, adolescents in the United States, and other regions with low vaccination rates, may benefit from even partial vaccination. Updated recommendations for less than three doses could also lead to reduced costs for developing countries as well as broader uptake and access to vaccination. In the United States, nearly half of girls age 13-17 have received two doses of the HPV vaccine.

The ability to also test women for HPV is changing the approach to screening for cervical cancer, especially as more and more women are being vaccinated against HPV.

Since HPV is the direct cause of nearly all cervical cancers, women who are found to have HPV can be followed more closely to see if they clear the infection, or if they have or develop cancer or pre-cancer.

In the United States, the HPV test is most often recommended along with a standard Pap test in women 30 and older. This is called co-testing. In 2014, however, the FDA approved the stand-alone HPV test as a method of cervical cancer screening, and certain professional organizations now strongly suggest that the HPV test can be used on its own as an effective alternative to standard Pap tests in most women being screened for cervical cancer.

In Australia, the National Cervical Screening Program will implement a switch in 2017 from Pap testing every two years for those age 18-69, to HPV screening alone every five years for those between the ages of 25-74. This screening transition is expected to continue to reduce cervical cancer mortality while vastly reducing the burden on women.

Fewer numbers of doctor visits and stressful, time-consuming follow-ups for positive screening tests will be a major saving for women. Improving our ways of summarizing such benefits of HPV vaccination across life from 18 to 69 could help frame vaccination as a benefit to women far beyond just reducing cervical cancer incidence.

Screening for Cervical Cancer: Is the HPV Test a Good Alternative to the Pap Test?

By Sarah Cortez

New guidelines from two professional medical organizations strongly suggest that the HPV (human

Pap test micrograph. Photo: Flickr/euthman

papilloma virus) test can be used on its own as an effective alternative to standard Pap tests in most women being screened for cervical cancer.

For seventy years, the Pap test has been the standard tool used to screen for cervical cancer. And it’s been one of cancer’s great success stories, with rates of new cases and deaths from cervical cancer dropping significantly both in the United States and abroad since it was first introduced. The Pap test finds abnormalities in the cells of the cervix that may be cancer or pre-cancer. These abnormalities can then be treated or followed closely over time.

The HPV test has been used alongside the Pap test for a number of years but was only recently approved by the FDA as a stand-alone test that could be used by itself, in place of the Pap test or Pap test plus HPV test combination.

As we’ve written about here on Cancer News in Context,  HPV causes the vast majority of cervical cancers. It is acquired through sexual contact and is actually very common. Over 75 percent of sexually active adults will get HPV at some point in their lives. Most healthy individuals successfully fight off the virus, but in some cases the virus lingers for years causing cervical changes that can ultimately lead to cervical cancer. So for the same reason that the HPV vaccine has the potential to prevent cervical cancer, an HPV test can help identify who is not clearing the virus and has the potential to develop cervical cancer.

The new guidelines from the Society of Gynecologic Oncology (SGO) and the American Society for Colposcopy and Cervical Pathology (ASCCP) appear in the journal Gynecology Oncology and state that, starting at age 25, doctors could use the HPV test as an alternative to the Pap test for cervical cancer screening.

Panel members from the ASCCP, SGO, as well as numerous other societies, reviewed eleven recent papers about the HPV test to answer the question: Is HPV testing by itself a safe, effective alternative to Pap testing?

They concluded that the HPV test is more accurate at ruling-out cervical cancer than the Pap test, meaning the HPV test is very good at telling when you don’t have cancer or pre-cancer.

They also concluded that it is just as good as a Pap test at finding those women with cancer or pre-cancer. However, the HPV test is also more prone to false positive screens – telling women there may be a problem when there isn’t one. As we stated before, most sexually active women acquire HPV at some point, but it usually goes away on its own. Since the HPV test simply detects HPV, it can identify women who have HPV but who do not have pre-cancer or cancer. As you can imagine, a false positive can cause a lot of anxiety as well as the need for extra testing to determine that the woman does not have pre-cancer or cancer.

So how does the panel recommend we manage women who are found by the test to have HPV? For these women, the panel states that the next step is to determine the specific type of HPV they are carrying. Two known types of HPV are much higher risk than others. These are HPV 16 and HPV 18, and they are responsible for over 70 percent of all cervical cancers.

• If you have an HPV type that is not HPV 16 or 18, then you are followed up with a standard Pap test. 

• If you do have HPV 16 or 18, then you are followed up with a colposcopy, which is the standard test after an abnormal Pap test. In a colposcopy, a doctor looks at the cervix with a special light and takes a tissue sample if something looks abnormal.

The panel found that using this screening approach increased the number of pre-cancers detected by 54 percent, but at the cost of doubling (200 percent) the number of colposcopies performed on women. This is a large increase in follow up colposcopies, and we do not know if the extra pre-cancers detected by HPV screening would have actually become cancerous.

Are there arguments against using the HPV test by itself to screen for cervical cancer? 

In short: yes.  Not all physicians or professional organizations endorse the new guidelines. At this point, the American College of Obstetricians and Gynecologist does not support the use of the HPV test as a main screening tool because they feel it will yield too many false positives - and bringing with them increased anxiety and follow up tests. Some physicians also worry that the HPV test could miss those rare cases of cervical cancer that may not be caused by HPV.

Even those not convinced that the HPV test should currently be used as an alternative to the Pap test, see its future potential.  Dr. Stewart Massad, Washington University Gynecologic Oncologist, sees a potential benefit in using the HPV test in those women who have previously received the HPV vaccine.

“Benefits of primary HPV screening will probably be greatest for young women who were vaccinated against HPV prior to initiating sexual activity. These vaccinated women have a much lower risk of infection with high risk HPV types, so they should require many fewer colposcopies, biopsies, and treatments.”

The panel concludes that while screening with the HPV test is an acceptable option to the standard Pap test, screening with the Pap test is also perfectly fine.

Cervical cancer is a serious disease that kills more than 4,000 women every year. Studies will continue to look at the long-term impact of the HPV test on cervical cancer diagnoses and outcomes. As these details continue to be worked out and discussed, what remains most important is that women see their gynecologists, get screened regularly for cervical cancer (see current ACS recommendations below), and vaccinate their adolescent children (both boys and girls) against HPV.  If you have questions about cervical cancer screening or HPV, your doctor is always the best source of information.


American Cancer Society - Cervical Cancer Screening Guidelines
Source: American Cancer Society Guidelines for the Early Detection of Cancer

Cervical cancer screening (testing) should begin at age 21. Women under age 21 should not be tested.

• Women between ages 21 and 29 should have a Pap test every 3 years. HPV testing should not be used in this age group unless it is needed after an abnormal Pap test result.

• Women between the ages of 30 and 65 should have a Pap test plus an HPV test (called “co-testing”) every 5 years. This is the preferred approach, but it is also OK to have a Pap test alone every 3 years.

• Women over age 65 who have had regular cervical cancer testing with normal results should not be tested for cervical cancer. Once testing is stopped, it should not be started again. Women with a history of a serious cervical pre-cancer should continue to be tested for at least 20 years after that diagnosis, even if testing continues past age 65.

• A woman who has had her uterus removed (and also her cervix) for reasons not related to cervical cancer and who has no history of cervical cancer or serious pre-cancer should not be tested.

• A woman who has been vaccinated against HPV should still follow the screening recommendations for her age group.

Some women – because of their health history (HIV infection, organ transplant, or DES exposure, etc.) – may need to have a different screening schedule for cervical cancer. Talk to your doctor or nurse about your history.

More CNiC posts on HPV

References

Huh WK, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: Interim clinical guidance. Gynecol Oncol (2015)

Frumovitz, M. Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis. UpToDate (2014).