Human papillomavirus (HPV) causes most cases of cervical cancer. Cervical cancer not caused by HPV is called HPV-negative cervical cancer and accounts for roughly 5% of all cervical cancer cases.

The statistic above comes from a 2021 review of HPV-negative cervical cancer.

Human papillomavirus (HPV) is a sexually transmitted infection that includes low risk and high risk HPV types. Some types of high risk HPV can cause cervical cancer.

Cervical cancer screening can show whether people have high risk HPV types, which may increase the risk of cervical cancer.

HPV-negative cervical cancer is negative for HPV types relating to cervical cancer. This may occur due to genetic mutations, misclassification of test results, or false-negative test results.

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More than 9 in 10 people with cervical cancer develop it due toHPV. However, the HPV vaccination prevents nearly all HPV-related cancers, and attending regular cervical cancer screenings can help detect abnormal changes early.

HPV infections are widespread, and there are many different types. According to the Centers for Disease Control and Prevention (CDC), researchers have identified 13 types of HPV that can cause cervical cancer.

Oncogenic HPV is the term for certain types of HPV that can cause cancer.

The immune system typically gets rid of an HPV infection naturally, usually within 2 years of contracting it. However, if someone contracts an oncogenic HPV type that the immune system cannot get rid of, it may lead to cell changes that can lead to cancer.

Around 10% of people with an HPV infection affecting the cervix will have long-term HPV infections, which can increase the risk of cervical cancer.

According to the National Cancer Institute, HPV test results from cervical screening show whether any high risk HPV types are present in cells of the cervix.

HPV results will either be positive or negative. A negative HPV test result means that the test found no high risk HPV types.

A positive result means that the test found high risk types of HPV in the cervix, and people may require further testing.

According to a 2021 review, around 5.5–11% of all cervical cancers worldwide are HPV-negative. However, a recent study using next-generation sequencing (NGS) found this figure closer to 5%. Some of these people may have true negative test results for high risk HPV, while others may have false-negative results.

A false-negative HPV result means that HPV types relating to cervical cancer are present, but the test does not indicate this.

It is rare for cervical cancer to be truly HPV-negative. The research around HPV testing and cervical cancer suggests the actual rate of HPV-negative cervical cancer may be lower than some estimates propose.

According to the 2021 review, HPV-negative cervical cancers have no apparent cause. HPV-negative cervical cancer does not link to an HPV infection. Possible causes of true HPV-negative cervical cancer may be due to mutations in specific genes.

HPV-negative cervical cancer may occur due to the spread of other cancers, such as endometrial cancer or HPV-negative cancer, in other areas of the body.

Some HPV-negative cancers may occur due to false-negative results as a result of the following:

  • incorrect classification of results after microscopic examination of tissues and cells of the cervix
  • a latent HPV infection due to a dormant HPV infection
  • non-high-risk HPV infection causing cervical cancer, which may occur in 1–2% of people with cervical cancer
  • HPV testing methods

Can doctors mistakenly diagnose HPV-negative cervical cancer?

Research indicates that doctors misdiagnosed almost 68% of HPV-negative cervical cancers as primary cervical cancer. HPV-negative cervical cancer may appear similar to endometrial cancer, which can spread to the cervix.

Detailed testing of the tumor and surrounding tissues is important to identify whether the cancer cells are cervical cancer, endometrial cancer, or from another area of the body.

People with HPV-negative cervical cancer may not receive a diagnosis until a later stage of the disease, making treatment more challenging.

Doctors use the International Federation of Gynecology and Obstetrics (FIGO) staging system to diagnose cervical cancer stages. Doctors may diagnose HPV-negative cervical cancer at an advanced FIGO stage.

Stages of cervical cancer range from 1-4, with the higher numbers representing a more advanced stage of the disease, and may indicate the cancer has spread to surrounding or distant areas of the body.

Treatment may depend on the stage of the cancer and whether people want to maintain fertility or not, but may include:

According to a 2022 review, no specific treatment for HPV-negative or positive cervical cancer exists. HPV-negative tumors vary from HPV-positive tumors and may spread to lymph nodes at an earlier stage or to more distant areas of the body.

There is a lack of evidence around HPV-negative cervical cancer treatment and outlook. Researchers require further evidence to assess the best treatment options and factors affecting a person’s outlook.

HPV-negative cervical cancer is rare. It may result from a misdiagnosis of primary cancer, false-negative HPV test results, or a non-HPV-related cause, such as gene mutations.

HPV vaccination can help prevent HPV types that cause cervical cancer, and attending regular cervical cancer screenings can help to detect abnormal changes earlier.