Can You Get Cervical Cancer Without HPV? Experts Explain Rare but Possible Cases

Cervical cancer is the fourth most common cancer among women globally, but the question remains as to the causes—especially where there is no HPV. Although Human Papillomavirus (HPV) is responsible for the majority of instances, can you have cervical cancer without it?

Here in this article, we condense the facts about HPV-negative cervical cancer, risk factors, and how you can stay safe—yes, even if you're negative for HPV.

Cervical Cancer and HPV: What's the Connection?

Nearly 99% of cervical cancer is caused by HPV according to the World Health Organization (WHO), a group of more than 200 related viruses. Some types, known as high-risk HPV types, can cause cervical cell changes leading to an increased risk of cancer.

HPV caused 620,000 cancer cases in women and 70,000 in men in 2019 alone, the vast majority of which are in the cervix.

HPV infections in the majority of cases spontaneously resolve, while persistent high-risk HPV infection can lead to cancer of the cervix, vulva, vagina, penis, anus, and even throat.

Is Cervical Cancer Possible Without HPV?

Yes, but it's a rare phenomenon.

As stated by Dr. Shailly Sharma, Senior Consultant - Gynaecology and Associate Director at Cloudnine Hospital, Faridabad, 3–5% of cervical cancers are HPV-negative. These are exceptional cases and could be due to:

• Testing errors or false negatives
• HPV-independent cancer pathways exclusive to cervical cancer
• Aggressive or fast-growing subtypes of cervical cancer

A 2022 BMB Reports study found that even though early research had shown up to 13% of cases as HPV-negative, improved testing procedures have lowered the number to 3–8%, and significantly less using more advanced tests.

 "HPV-negative cervical cancers would be of a different nature and might be more aggressive or harder to detect early on," says Dr. Sharma.

Other Cervical Cancer Risk Factors (excluding HPV)

Even though HPV is still the main cause of cervical cancer, other factors are likely in HPV-negative cervical cancer:

1. Genetic Mutations

Genetic mutations in genes such as TP53 or PTEN may lead to abnormal cell growth.

2. Dysfunctional Immune System

A weakened immune system may fail to recognize and destroy abnormal cells.

3. Heavy Smoking

Smoking is an established risk factor that damages cervical cells and interferes with immune function.

4. Chronic Inflammation

Chronic inflammatory diseases may possibly increase cancer risk.

5. Other Infections

Other viruses like Herpes Simplex Virus (HSV), Epstein-Barr Virus (EBV), or chlamydia have been studied, but none have been reported to cause cervical cancer in the absence of HPV.

Can Pap Smears Detect HPV-Negative Cervical Cancer?

Yes—Pap smear tests are still necessary, even for individuals who receive a negative HPV test.

"Pap smears examine cell changes in the cervix, whether or not there is HPV," explains Dr. Sharma. 

When combined with HPV testing, co-testing is a potent screening tool to identify early warning signs.

Regular screening is critical—even if your HPV test is negative.

How to Lower Your Risk of Cervical Cancer

Self-protection against cervical cancer entails more than just an HPV test. Here's how you can do it:

✅ Have regular Pap smears and HPV tests as advised.

✅ Take the HPV vaccine, even though it won't be able to prevent HPV-negative cancers—it will guard against most of them.

✅ Don't smoke and try to limit alcohol consumption.

✅ Use safe sex to limit contact with high-risk viruses.

✅ Boost your immune health by balancing your diet, exercising, and keeping stress in check.

Last Word: Be Informed, Be Safe

While HPV is the cause of most cervical cancers, HPV-negative cases exist as well. That's why one must remain on schedule with regular Pap smears, follow the recommendation of one's physician, and be a healthy person.

Regardless of whether you're HPV-positive or HPV-negative, early detection is your best defense.