HPV-Negative Cervical Cancer

HPV-Negative Cervical Cancer
31 Jan 2024
9 minutes
Table Of Content
HPV-Negative Cervical Cancer



    Welcome, everyone, to another episode of our blog on cervical cancer. January is designated as a cervical cancer awareness month. There has always been a lack of understanding, underlying hesitations, and restricted access to medical care that has made this a significant concern for women across the globe. Let us raise our voices in spreading awareness against the carcinogenic beast that affects our female fighters. Join with us and get enlightened on the insights about cervical cancer. In this blog, we will dive into the untold story of cervical cancer, namely Human papillomavirus-negative cervical cancer, which is the hidden devil behind the dark. 


    Human Papillomavirus and Cervical Cancer: Decoding the link


    Cervical cancer is the fourth most common cancer across the world, which is responsible for causing 342000 deaths worldwide in 2020. Human papillomavirus is the most common sexually transmitted disease. The human immune system usually gets rid of the invading HPV naturally over a period of time, but there are times when we get infected with HPV with an oncogenic type that remains in the body and changes normal functioning cells into the tumor cells leading to cancers. Researchers have identified 13 different types of HPV that can cause cervical cancer. 

    Most cases of cervical cancer are caused mainly by HPV infections. Currently there is no clear definition for HPV-negative cervical cancer, but there are certain conditions where cervical cancer is caused other than the underlying human papillomavirus infection. This condition is called HPV-negative cervical cancer. About 5.5- 11% of cases are reported to be of HPV-negative cervical cancer. However, it is rare for cervical cancer to be an HPV-negative one. 




    1. HPV truly negative cervical cancer:

    These types of cancer have their independent pathogenesis and occurrence; the diagnosis often involves observation of histological features, cytological screening, and staining methods. Treatment planning often involves, further studies associated with their pathways and biomarkers. 

    2. HPV false negative cervical cancer:

    False negatives arise mainly due to an error in the screening procedures involved in HPV detection; often, retesting with other alternate HPV detection methods will reduce the false negatives. 

    Causes of HPV- negative cervical cancer


    1. Tobacco smoking: The carcinogens that are present in tobacco can directly damage the cervical cells, posing a major threat for HPV negative type of cervical cancer.
    2. Genetic factors: Certain genetic variations, mutations, and alterations in the DNA can contribute to developing a negative type of cervical cancer.
    3. Incorrect results after the screening test for HPV.
    4. An underlying latent HPV infection that does not show any signs of activity.
    5. HPV infection-independent cervical cancer - cervical cancer caused by mutations in tumor genes rather than underlying HPV infection.
    6. Misclassification of non-cervical cancer: About 68% of negative HPV cancers are misdiagnosed as primary cervical cancer.
    7. Poor cell viability and loss of cellular fragments of papillomavirus can result in false outcomes.

    Symptoms of HPV-negative cervical cancer


    Patients experience similar symptoms associated with HPV-positive cervical cancer. However, it is vital to keep in mind that the early stages of any cervical cancer will exhibit no symptoms at all. 

    1. Abnormal vaginal bleeding occurs in between menstrual periods, after intercourse.
    2. Unusual vaginal discharge
    3. Pain during urination
    4. Pelvic pain
    5. Pain in lower back and legs
    6. Weight loss over a period of time
    7. Fatigue

    Treatment of HPV-negative cervical cancer


    The patient should be staged according to TNM classification [tumor type, lymph node involvement, metastasis involved], and the FIFO stage should be recorded. Currently, there are no specific treatment strategies for treating HPV-negative cervical cancer; the treatment protocol often involves similar therapy in accordance with HPV-positive cervical cancer. Some of the treatment strategies involved are, 


    Surgical procedures like radical hysterectomy, which include the removal of the uterus, and cervix, also involve the removal of ligaments and the uppermost parts of the vagina. It is recommended in the early stages of cervical cancers.


     Chemotherapy methods may be employed as adjuvant [after the surgery] or neoadjuvant type [ before the surgery] to reduce the risk of recurrence. 

    Radiation therapy:

    There are two types of radiation, namely external beam and internal radiation therapy involving brachytherapy, which involves the use of an implant of radiation source near the tumor site. It is used to treat locally advanced cervical cancer.


    Chemotherapy and radiation therapy are often used mostly in conjugation along with surgical interventions. Incorporating a proper diet that helps prevent cervical cancer is also a major approach in management. 


    Prognosis of HPV-Negative Cervical Cancer and Survival rate


    The prognosis of cervical cancer depends upon the early detection of the tumor cells and the development of individualized treatment patterns. However, this is not the case with the patients identified as HPV-negative cervical cancers. The reason lies in the way cervical cancer itself is asymptomatic, and people with negative HPV infections are being identified in advanced stages of cervical cancer, which restricts the disease-free survival rate compared to the patients with HPV-positive cancer. The risk recurrence was 2.6 times higher, and the risk of distant metastasis was 4.5 times higher in HPV-negative patients compared to their counterparts. 

     Myths And Facts

    Just like every other disease there are numerous myths that surround cervical cancer. Let us burst some of the myths below. 


    Myth: Only sexually active women tend to develop cervical cancer.

    Fact: Sexual activity tends to increase the risk of HPV infection, but there are other underlying causes like smoking, a weakened immune system, and certain genetic modifications that are also responsible for causing cervical cancer.


    Myth: Receiving the HPV vaccine eliminates the need to be screened for cervical cancer.

    Fact: HPV vaccination does not offer protection against all types of HPV infections. Regular screenings including Pap smears and HPV sensitivity tests are recommended. 


    Myth: Pap smears are a painful procedure.

    Fact: Pap smears are quick, painless, and simple procedures performed only by a trained healthcare professional to ensure the patient's safety and privacy.




    Guiding the patients through complete knowledge about early detection and associated risk factors is a vital tool that is essential in the management of HPV-negative cervical cancers. Regular screenings and early HPV vaccination reduce the risk of cervical cancer. In this cervical cancer awareness month, let's spread awareness and take a pledge for a cancer-free world. 


      Determined hearts, cancer-free starts!

    Written by
    Dr. Thamizhakaran K SMedical Content Writer
    AboutThamizhakaran K S is a Medical Content writer at Mr.Med. He completed Doctor of pharmacy from Annamalai University in 2023. He has worked as clinical pharmacist intern at Government Cuddalore medical college and hospital. During internship he gained expertise on clinical pharmacology, pharmacotherapeutics and clinical research. He also published an research project in International Journal of Pharmacy and Pharmaceutical Research. He has thorough knowledge on clinical trial methodologies and various pharmacovigilance guidelines. He possesses a strong interest in writing and uses his research skills to clearly communicate health information to the readers.
    Tags :Human papillomavirus cervical cancerHPV negative cervical cancer