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by Dr. C.H. Weaver 10/2021

The recommendations for the new guidelines were composed from four panels: a gynecologic cancer advisory group; a work group on interval, older women and hysterectomy; a when to start screening work group; and a work group on technologies who all reviewed and deliberated medical evidence regarding the screening for cervical cancer.

Cervical CancerConnect 490

The HPV test is better than the PAP Smear

Cervical cancer accounts for 6% of all cancers in women, and approximately 15,000 women are diagnosed with cervical cancer each year in the United States - roughly 5,000 women die annually from this disease. Screening for abnormal, precancerous or cancerous cells in the cervix is critical for prevention, early detection and diagnosis of cervical cancer.

The Pap test had long been the standard for cervical cancer screening. During a Pap test a sample of cells from the cervix is taken with a small wooden spatula or brush and examined under the microscope. Patients who have abnormal Pap test results may receive additional follow-up tests, such as colposcopy or biopsy. However, studies have suggested cytology-based screening using PAP is less efficient for those who have undergone HPV vaccination, resulting in a high rate of false-positive results.

The human papillomavirus (HPV) test detects the presence of human papillomavirus, a virus that can lead to the development of genital warts, abnormal cervical cells or cervical cancer. An test detects evidence of an infection with a high-risk strain of HPV. There are over 100 known strains of HPV, only some of which are spread through sexual contact. Sexually-transmitted HPV strains are separated into two categories:

  • Low-risk HPV: Low-risk strains of HPV are rarely linked with cancer. While most low-risk HPV infections cause no disease, some strains of low-risk HPV can cause warts on the genitals and anus or in the mouth and throat. Doctors can typically diagnose low-risk HPV based on a patient’s symptoms, so testing for these strains is not performed.
  • High-risk HPV: Researchers have identified around 14 strains of high-risk HPV. These strains can cause cancer. HPV testing indicates whether a person is currently or has been infected with a high-risk strain, but not every HPV test identifies the specific strain of HPV causing an infection. Determining the specific strain of HPV is called HPV genotyping.

Types of HPV tests generally fall into three categories:

  • HPV DNA testing: In HPV DNA testing, a patient’s cells are examined in a laboratory for the genetic material (DNA) of HPV. If evidence of HPV is detected, HPV genotyping may be performed to determine the specific strain of HPV causing infection.
  • HPV ribonucleic acid (RNA) testing: In HPV RNA testing, a sample of cells is examined in a laboratory for a different type of genetic material called RNA. This test offers improved specificity compared to HPV DNA testing, reducing the amount of false positives and unnecessary follow-up. HPV RNA testing may also include HPV genotyping.
  • Detection of cellular markers: Unlike other types of HPV testing, cellular marker detection doesn’t look for the genetic material of the HPV virus. Instead, this type of testing looks for evidence of two proteins called p16 and Ki-67. The amount of these proteins are elevated in cell samples that are infected with the HPV virus.

Understanding Test Results

  • Positive HPV test. A positive test result means that you have a type of high-risk HPV that's linked to cervical cancer. It doesn't mean that you have cervical cancer now, but it's a warning sign that cervical cancer could develop in the future. Your doctor will probably recommend a follow-up test in a year to see if the infection has cleared or to check for signs of cervical cancer.
  • Negative HPV test. A negative test result means that you don't have any of the types of HPV that cause cervical cancer.
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What Next?

Depending on your test results, your doctor may recommend one of the following as a next step:

  • Normal monitoring. If you're older than age 30, and your HPV test is negative and your Pap test is normal, you'll follow the generally recommended schedule for repeating both tests in five years
  • Colposcopy. In this follow-up procedure, which is recommended if your Pap test is abnormal, your doctor uses a special magnifying lens (colposcope) to more closely examine your cervix.
  • Biopsy. In this procedure, usually done at the same time as colposcopy, your doctor takes a sample of cervical cells (biopsy) to be examined more closely under a microscope.
  • Removal of abnormal cervical cells. To prevent abnormal cells from developing into cancerous cells, your doctor may suggest a procedure to remove the areas of tissue that contain the abnormal cells.
  • Seeing a specialist. If your Pap test or HPV test results are abnormal, your doctor will probably refer you to a gynecologist for a colposcopic exam. If test results show that you might have cancer, you may be referred to a doctor who specializes in treating cancers of the female genital tract (gynecologic oncologist) for treatment.

Who Should be Tested?

The National Cancer Institute recommends that women over the age of 18 or those sexually active before the age of 18 should be screened for cervical cancer annually. Women at an increased risk of developing cervical cancer should be particularly diligent in their annual screening. Risk factors include early age at first intercourse (16 or younger), history of multiple sexual partners, smoking and poor nutrition. In addition, a history of sexually transmitted diseases, such as chlamydia, human immunodeficiency virus (HIV), and especially HPV appear to increase the risk of developing cervical cancer. Thirteen different HPVs (wart-causing viruses) have been linked to almost every case of cervical cancer. However, the converse is not true, as the presence of HPV does not guarantee that cervical cancer will develop.

The FDA approved the HPV test in 2014 as a primary screening tool because it is superior to the Pap test. Research suggests that women screened for cervical cancer via primary HPV testing had a lower likelihood of developing cancerous lesions than women who underwent standard PAP based cytology testing. Updated guidelines issued by the American Cancer Society (ACS) in July 2020 now recommend that cervical cancer screening with the HPV test be performed every 5 years beginning at age 25 and continuing to 65 years.1

The recommendation relies solely on the HPV test as the preferred test and phases out the Pap test and co-testing with the Pap test and HPV testing. Not all physicians are in agreement with the recommendation citing research that HPV testing alone misses twice as much cervical cancer as co-testing. Women should discuss the role of co-testing with their doctor.2

Screening Reccomendatons

  • Those aged 25 to 65 should have a primary HPV test every 5 years. If primary HPV testing is not available, screening may be done with either a co-test that combines an HPV test with a Papanicolaou (Pap) test every 5 years or a Pap test alone every 3 years.
  • Screening is not recommended for women over 65 who have had at least three consecutive negative Pap tests or at least two negative HPV tests in the past 10 years, with the most recent test in the past 5 years. Women in this age group who have a history of cervical pre-cancer (CIN2 or a more severe diagnosis) should continue routine screening for at least 20 years, even if this extends beyond age 65.
  • Women who have undergone a hysterectomy (with removal of the cervix) for reasons not related to cervical cancer or pre-cancer should no longer be screened.
  • Women who have been vaccinated against HPV should follow the age-specific recommendations in these guidelines (for unvaccinated women). Currently, there are no alternative screening recommendations for women vaccinated against HPV
Cervical Cancer Newsletter 490

References:

  1. The American Cancer Society Guidelines for the Prevention and Early Detection of Cervical Cancer.
  2. Kaufman HW, et al. Am J Clin Pathol. 2020.doi:10.1093/ajcp/aqaa074.
  3. ACOG statement on cervical cancer screening guidelines. Available at: www.acog.org/news/news-releases/2020/07/acog-statement-on-cervical-cancer-screening-guidelines. Accessed Oct. 5, 2020.