Most cervical cancer is caused by HPV, but a small number of cases develop without it

The short answer is yes—cervical cancer can develop without human papillomavirus (HPV), though it is uncommon. HPV causes roughly 90 percent of cervical cancers, but the remaining cases arise from other causes, including a weakened immune system, long-term inflammation, or exposure to certain chemicals or radiation. Understanding this distinction matters because it affects how doctors screen for the disease and how they explain risk to patients.

If you have been told you have cervical cancer or are concerned about your risk, knowing whether HPV is involved can help you understand your diagnosis and what comes next. This guide explains how cervical cancer develops with and without HPV, what the other risk factors are, and what screening and prevention look like in each situation.

Key Takeaways

  • About 90 percent of cervical cancers are caused by HPV, but 10 percent develop from other causes such as immune system weakness or chronic inflammation.
  • Non-HPV cervical cancers are more common in people over 65, those with untreated HIV, and those exposed to diethylstilbestrol (DES) before birth.
  • Pap tests and HPV tests are designed to catch HPV-related cancers early and work less well for non-HPV types, so screening recommendations may differ.
  • Your doctor can test for HPV presence to determine which type of cervical cancer you have, which affects treatment planning.

How HPV causes most cervical cancers

HPV is a virus that spreads through sexual contact and infects the cells lining the cervix. Most people clear an HPV infection on their own within a year or two, but in some people the virus persists. Over many years—usually 10 to 20—persistent infection can cause the cervical cells to change and eventually become cancerous.

This process is why HPV testing and Pap tests (which look for abnormal cell changes) are so effective at preventing cervical cancer. Catching these changes early, before they turn into cancer, allows doctors to remove the abnormal tissue and stop the cancer from developing. HPV vaccination also prevents infection with the strains most likely to cause cancer, which is why it has dramatically reduced cervical cancer rates in countries with high vaccination rates.

What causes cervical cancer without HPV

Non-HPV cervical cancers develop through different pathways. Chronic inflammation of the cervix—from conditions like untreated pelvic inflammatory disease or long-standing infections—can lead to cell changes over time. A weakened immune system, particularly from untreated HIV, makes it harder for the body to control abnormal cell growth and increases the risk of cervical cancer regardless of HPV status.

Diethylstilbestrol (DES) exposure is another documented cause. DES was a synthetic hormone given to pregnant women between the 1940s and 1970s to prevent miscarriage. People exposed to DES before birth have an increased risk of a specific type of cervical cancer called clear cell adenocarcinoma, even without HPV infection. Radiation exposure—from cancer treatment to the pelvis or from occupational exposure—can also damage cervical cells and lead to cancer years later.

Certain adenocarcinomas (cancers that start in mucus-producing cells rather than the flat cells that line the cervix) are less likely to be HPV-related than squamous cell cancers. These account for a growing share of cervical cancers in developed countries, partly because Pap tests are better at catching squamous changes than glandular changes.

Who is at higher risk for non-HPV cervical cancer

Non-HPV cervical cancers are more common in certain groups. People over 65 make up a larger share of non-HPV cases, possibly because screening rates drop after menopause and because immune function changes with age. People with untreated or advanced HIV have significantly higher rates of cervical cancer, including both HPV-related and non-HPV types.

People born between 1940 and 1971 who were exposed to DES in the womb face a documented increased risk. People who have received pelvic radiation for other cancers, or who work in environments with chemical or radiation exposure, also carry higher risk. Additionally, people who have never been screened or who have had inconsistent screening are more likely to develop cervical cancer of any type, since early detection is missed.

How doctors test for HPV and determine cancer type

When cervical cancer is diagnosed, doctors typically perform an HPV test on the tissue sample to determine whether the cancer is HPV-related. This test looks for the genetic material of HPV in the cancer cells. A positive result means HPV was involved; a negative result suggests the cancer developed through another pathway.

Doctors also examine the cancer cells under a microscope to identify the type—whether it is a squamous cell cancer (which accounts for about 80 percent of cases) or an adenocarcinoma (about 15 percent). The combination of HPV status and cell type helps guide treatment decisions and prognosis. Some cancers are also tested for other genetic changes that may affect which drugs work best.

Screening and prevention when HPV is not involved

Standard cervical cancer screening—Pap tests and HPV tests—is designed to catch HPV-related changes before they become cancer. These tests are less effective at finding non-HPV cancers, particularly adenocarcinomas, because the abnormal cells are located deeper in the cervix or in the glandular tissue where a Pap brush may not reach them as easily.

This is one reason why screening guidelines recommend stopping routine Pap tests at age 65 if you have had consistent normal results—the risk of HPV-related cancer drops significantly. However, people at higher risk for non-HPV cancers (such as those with untreated HIV or a history of pelvic radiation) may benefit from continued screening or more frequent screening, even after 65. Your doctor can discuss what screening schedule makes sense for your individual situation.

Prevention of non-HPV cervical cancers focuses on managing the underlying risk factors: treating HIV promptly, avoiding pelvic radiation when possible, and addressing chronic infections or inflammation. HPV vaccination does not prevent non-HPV cancers, but it remains important for preventing the majority of cervical cancers.

What happens after a non-HPV cervical cancer diagnosis

Treatment for non-HPV cervical cancer follows the same general approach as HPV-related cancer: surgery, radiation, chemotherapy, or a combination, depending on the stage and type of cancer. However, some non-HPV cancers may respond differently to certain drugs. Adenocarcinomas, for example, are sometimes treated differently than squamous cell cancers because they tend to be diagnosed at a later stage.

Your oncologist will discuss your specific diagnosis, stage, and treatment options with you. Knowing whether your cancer is HPV-related or not helps them predict how it may behave and which treatments have the strongest evidence behind them. Follow-up care and monitoring after treatment are similar regardless of HPV status, though your doctor may adjust screening recommendations based on your individual risk factors.

Frequently Asked Questions

If I test negative for HPV, does that mean I cannot get cervical cancer?

No. A negative HPV test means you do not currently have a persistent HPV infection, which is the most common cause of cervical cancer. However, you could still develop cervical cancer from other causes such as immune system weakness, chronic inflammation, or previous radiation exposure. This is why screening continues even for people with negative HPV tests, particularly if they have other risk factors.

Can I get cervical cancer if I have been vaccinated against HPV?

HPV vaccination prevents infection with the strains most likely to cause cervical cancer, but it does not protect against all HPV types or against non-HPV causes of cervical cancer. The vaccines currently in use protect against 9 HPV types, but there are many others. Additionally, vaccination does not prevent the small percentage of cervical cancers that develop without HPV. Screening remains important even for vaccinated people.

Does having untreated HIV increase my risk of non-HPV cervical cancer?

Yes. People with untreated or advanced HIV have higher rates of both HPV-related and non-HPV cervical cancers because a weakened immune system cannot control abnormal cell growth. Starting and staying on HIV treatment (antiretroviral therapy) significantly reduces this risk. People with HIV should discuss cervical cancer screening with their doctor, as recommendations may differ from those for people without HIV.

What is DES and why does it increase cervical cancer risk?

DES (diethylstilbestrol) was a synthetic hormone given to pregnant women from the 1940s to 1970s to prevent miscarriage. People exposed to DES before birth have an increased risk of clear cell adenocarcinoma of the cervix, a specific type of cancer that is often not HPV-related. If you were born during this period and your mother took DES, discuss your screening needs with your doctor.

How often should I be screened if I am at risk for non-HPV cervical cancer?

Screening recommendations depend on your specific risk factors and your medical history. People with untreated HIV, a history of pelvic radiation, or DES exposure may need more frequent screening or screening that continues past age 65. Talk with your doctor about your individual risk factors so they can recommend a screening schedule that is right for you.