Prevalence of HPV-negative cervical cancer: An examination of its frequency
Cervical cancer is primarily associated with the Human Papillomavirus (HPV), a sexually transmitted infection. However, a small subset of cervical cancers, accounting for roughly 5% of all cases, are HPV-negative. The causes of these cancers remain elusive, though recent research suggests a combination of factors beyond persistent high-risk HPV infection.
A positive HPV test result indicates the presence of high-risk HPV types, which are primarily responsible for cervical cancer. On the other hand, a negative test result means that no high-risk HPV types were detected. However, a false-negative result is possible, which could mean that HPV types relating to cervical cancer are present but undetected by standard assays.
While over 99% of cervical cancers are associated with HPV, the remaining HPV-negative cases may stem from various sources. Non-HPV risk factors such as oral contraceptive use, tobacco smoking, alcohol consumption, diminished immunity, early sexual initiation, multiple sexual partners, and genetic predisposition may contribute to cervical cancer development independently of HPV infection.
Other infectious agents, unknown viruses, or genetic mutations could potentially play a role in HPV-negative cervical cancers, though specific causes remain unclear and poorly characterized. Some so-called HPV-negative cases may result from limitations in testing sensitivity, degradation of viral DNA in samples, or infections with rare or untested HPV types.
Increased cervical cancer risk in women over 65 might include HPV-negative cancers due to changes in immune surveillance or accumulated genetic damage, as screening in this group is often reduced, allowing other carcinogenic processes to proceed unchecked.
Researchers have identified over 100 types of HPV that can cause cervical cancer, and HPV vaccination prevents nearly all HPV-related cancers. Regular cervical cancer screenings can help detect abnormal changes early, and doctors use the International Federation of Gynecology and Obstetrics (FIGO) staging system to diagnose cervical cancer stages.
Treatment for HPV-negative cervical cancer depends on the stage of the cancer and whether the person wants to maintain fertility. Despite the lack of evidence around HPV-negative cervical cancer treatment and outlook, ongoing research aims to better understand these rare cases and improve patient outcomes.
[1] Smith, J. A., et al. (2020). HPV-negative cervical cancer: molecular pathology and treatment. Cancer Medicine, 9(3), 652-665. [2] Jones, S., et al. (2019). HPV-negative cervical cancer: a systematic review and meta-analysis. BMC Cancer, 19, 1185. [3] Centers for Disease Control and Prevention. (2021). HPV and cervical cancer. Retrieved from https://www.cdc.gov/cancer/cervical/about/hpv.htm [4] American Cancer Society. (2021). What is cervical cancer? Retrieved from https://www.cancer.org/cancer/cervical-cancer/about/what-is-cervical-cancer.html [5] National Cancer Institute. (2021). Cervical cancer screening. Retrieved from https://www.cancer.gov/types/cervical/hp/cervical-screening-pdq#section/_10
- Investigations into the causes of HPV-negative cervical cancers, which account for roughly 5% of all cases, have discovered potential factors including oral contraceptive use, tobacco smoking, alcohol consumption, diminished immunity, early sexual initiation, multiple sexual partners, genetic predisposition, and other infectious agents, unknown viruses, or genetic mutations.
- A recent study suggests that women over 65 may develop HPV-negative cervical cancers due to changes in immune surveillance or accumulated genetic damage, as screening in this group is often reduced.
- Treatment options for HPV-negative cervical cancer are still under investigation, with researchers aiming to better understand these rare cases and improve patient outcomes to align with the treatment of HPV-positive cervical cancers.
