99% of all cervical cancer cases are associated with an HPV infection, according to the WHO. HPV is not a single virus but a group of 200 known viruses that not only increase a person's risk of different types of cancers but also lead to genital warts and infections. While in 90% of the cases, the body controls the virus by itself, persistent infections with high-risk HPV types can increase the risk of cervical, vulvar, vaginal, oral, penile, and anal cancer.

In 2019 alone, HPV was responsible for an estimated 6.2 lakh cancer cases in women and 70,000 cases in men, according to the WHO.

The short answer is yes. According to Dr Sharma, while cervical cancer in individuals who test negative for HPV is quite rare, it can still occur. She shared that a small percentage, estimated around 3–5%, of cervical cancers are HPV-negative. “These cases may be due to misdiagnosis, technical errors in testing, or truly HPV-independent disease pathways.”

A 2022 study published in the highlighted that while most cases of cervical cancer are due to HPV, around 3–8% are HPV-negative — and this number drops further with more accurate testing.

Older studies reported up to 13% of cases as HPV-negative, but many were due to false negatives or misclassification. More sensitive methods, like multiplex PCR, show the true rate is closer to 5%.

“Though uncommon, HPV-negative cervical cancers tend to behave differently and may be more aggressive or harder to detect early,” Dr Sharma added.

While HPV is the primary cause of cervical cancer, research has explored the potential roles of other infections such as Herpes Simplex Virus (HSV), Epstein-Barr Virus (EBV), and chlamydia trachomatis, said Dr Sharma. However, she shared that their contribution to cervical cancer remains unclear and not well-established. “None of these infections alone are proven to cause cervical cancer in the absence of HPV. The medical consensus remains that persistent infection with high-risk HPV types is the central cause.”

In HPV-negative cervical cancer, genetics and lifestyle factors may play a larger role in increasing people’s risk of the disease. Genetic mutations, such as changes in the TP53 or PTEN genes, can influence abnormal cell growth in the cervix. In addition, lifestyle factors like long-term smoking, chronic inflammation, and weakened immunity may increase the risk.

While these are not direct causes, they may act as contributing factors in the development of cancer, especially in cases where HPV is not involved.

“Routine Pap smears can still detect cervical cancer that is not linked to HPV,” emphasised Dr Sharma.

According to her, a Pap smear evaluates the appearance of cervical cells and can identify abnormal or precancerous changes regardless of HPV status. “This is why Pap testing remains an important tool, especially when combined with HPV testing. In HPV-negative individuals, regular Pap smears provide a safety net for catching early signs of disease.”

It is important that HPV-negative individuals continue with their regular cervical cancer screening as recommended by their doctor. “Even if you test negative for HPV, it is important not to skip Pap smears, as they can detect non-HPV-related abnormalities,” highlighted Dr Sharma.

In addition, maintaining a healthy immune system, avoiding tobacco use, and practising safe sex are all helpful in reducing one’s risk of cervical cancer along with many other types of cancers.

While HPV vaccination won’t impact HPV-negative cancers directly, it’s still a valuable public health tool and recommended for most individuals to prevent the majority of cervical cancers.

While HPV is the leading cause of cervical cancer, it’s not the only factor. Whether you’re HPV-positive or HPV-negative, routine Pap smears remain the best way to catch abnormalities early and enable timely treatment. Staying informed, looking after your health, and following your doctor’s guidance can make all the difference in reducing your risk and protecting your overall health.