Human papillomavirus (HPV) is the most common sexually transmitted disease (STD) in the United States. Almost all sexually active people who do not receive an HPV vaccine will become infected with HPV at some point in their life.

An HPV test uses a sample of cells to determine whether the cells are infected with a high-risk strain of HPV. Such an infection, if long-lasting, can cause changes in cervical cells that could lead to cervical cancer.

An HPV test is primarily used to screen for the virus that causes cervical cancer but may also be used to plan treatment for patients diagnosed with oropharyngeal cancer, a type of cancer that affects the middle part of the throat.

Purpose of the test

The purpose of an HPV test is to detect an infection with a high-risk strain of HPV. An HPV test may be performed in several situations:

• Cervical cancer screening: Cancer screening tests look for cancer or precancerous conditions before a person experiences symptoms in order to detect them early when they are easier to treat. Most cervical cancers are caused by HPV. HPV testing allows patients infected with high-risk HPVs to be monitored effectively and to have any abnormal cervical cells removed before they develop into cancer. Cervical cancer screening is appropriate for anyone with a cervix, including women and transgender men who have a cervix.
• Follow-up: An HPV test may be used as a follow-up test after an abnormal Pap smear.
• Oropharyngeal cancer treatment planning: Oropharyngeal cancer is a type of cancer that begins in the tonsils or back of the throat. The majority of oropharyngeal cancers are caused by HPV. HPV-positive oropharyngeal cancers may be treated differently than HPV-negative oropharyngeal cancers, so HPV testing is an important part of treatment planning.

HPV infections can cause several other types of cancer, including cancers of the anus, penis, vagina, and vulva. However, HPV testing on these parts of the body is uncommon in the United States and is typically only performed for research purposes.

What does the test measure?

An HPV 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.

HPV test measurements depend on the specific type of HPV test that was performed. 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 number 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.

When should I get an HPV test?

When used as a test to screen for cervical cancer, how often a person should get an HPV test depends on their age, health, and their history of cervical cancer screening. Cervical cancer screening may involve a Pap smear, an HPV test, or co-testing with both tests at the same time.

Professional medical organizations offer cervical cancer screening recommendations. For example, the U.S. Preventive Services Task Force recommends that most people with a cervix undergo regular cervical cancer screening between ages 21 and 65:

• Ages 21 to 29: Most people with a cervix between 21 and 29 years old should get screened for cervical cancer every three years with a Pap smear alone. Many expert groups don’t recommend HPV testing in this age group because HPV is exceedingly common in young people, and most HPV infections resolve without treatment, so a positive test may be misleading. It also takes many years for an HPV infection to cause cancer.
• Ages 30 to 65: For people with a cervix between 30 and 65 years old, there are several options for cervical cancer screening. Patients in this age group may choose to be screened every three years with a Pap smear alone, every five years with an HPV test alone, or every five years with both a Pap smear and an HPV test.

Patients should have a discussion with their health care provider about the pros and cons of different screening strategies in order to decide which approach is best for their situation.

Patients may need to be screened for cervical cancer more often if they have one of the following risk factors:

• A history of abnormal Pap smears
• HIV
• A mother who was exposed to diethylstilbestrol (DES) while pregnant
• A weakened immune system

Other groups do not need regular cervical cancer screening. These include:

• People under 21 years of age
• People older than 65 who have had an adequate screening in the past and are not at an increased risk of cervical cancer
• People who have had a hysterectomy and who do not have a history of abnormal Pap smears or cervical cancer

An HPV test may also be recommended as a follow-up test for patients who have had an abnormal Pap smear to help doctors understand if abnormal cell changes are related to an HPV infection and require additional follow-up.

In patients diagnosed with oropharyngeal cancer, HPV testing may be conducted on a tissue sample after a diagnosis of cancer is confirmed.

What is PCR?

Sometimes called "molecular photocopying," the polymerase chain reaction (PCR) is a fast and inexpensive technique used to "amplify" - copy - small segments of DNA. Because significant amounts of a sample of DNA are necessary for molecular and genetic analyses, studies of isolated pieces of DNA are nearly impossible without PCR amplification.

Often heralded as one of the most important scientific advances in molecular biology, PCR revolutionized the study of DNA to such an extent that its creator, Kary B. Mullis, was awarded the Nobel Prize for Chemistry in 1993.

What is PCR used for?

Once amplified, the DNA produced by PCR can be used in many different laboratory procedures. For example, most mapping techniques in the Human Genome Project (HGP) relied on PCR.
PCR is also valuable in a number of laboratory and clinical techniques, including DNA fingerprinting, detection of bacteria or viruses (particularly AIDS), and diagnosis of genetic disorders.

How does PCR work?

To amplify a segment of DNA using PCR, the sample is first heated so the DNA denatures, or separates into two pieces of single-stranded DNA. Next, an enzyme called "Taq polymerase" synthesizes - builds - two new strands of DNA, using the original strands as templates. This process results in the duplication of the original DNA, with each of the new molecules containing one old and one new strand of DNA. Then each of these strands can be used to create two new copies, and so on, and so on. The cycle of denaturing and synthesizing new DNA is repeated as many as 30 or 40 times, leading to more than one billion exact copies of the original DNA segment.

The entire cycling process of PCR is automated and can be completed in just a few hours. It is directed by a machine called a thermocycler, which is programmed to alter the temperature of the reaction every few minutes to allow DNA denaturing and synthesis."