The Pathology of Cervical Precancer and Cancer             

By Jane Meggitt 

Once, cervical cancer was the leading cause of cancer death in U.S. women. Nearly all cervical cancer results from infection by the human papillomavirus (HPV). Until recently, cytology-based screening via the Pap test was the sole method of screening for cervical precancer and cancer. While the Pap test significantly reduced the number of cervical cancer deaths, there are now other approaches informing diagnostic criteria in both cytology and histopathology. 

HPV Biology

The key to these new approaches focuses on an understanding of HPV biology. Such understanding was a long time coming, as four decades passed before the first characterization of types of HPV to general use in clinical studies.

Those early HPV studies via electron microscopy and immunochemistry eventually led to the cloning of these types. The cloning of nearly 70 HPV genomes was necessary before scientists determined a final HPV probe set for screening purposes. 

An HPV vaccine prevents new infections but does not affect existing infections. The hope is that employment of the vaccine and HPV testing will someday make cervical cancer a thing of the past. 

Cervical Precancer

Many women experience precancerous changes in the cervix. Such lesions may take years to develop into cancer, although some cancers may develop more quickly. This cervical dysplasia occurs most often in females in their 20s and 30s.

These precancerous conditions are identified based on the degree of abnormal appearance under a microscope, as well as the severity of these changes. Precancerous grouping is based on cell type abnormality. 

Cervical Cancer 

The majority of cervical cancers are squamous cell carcinomas. Less frequently, it is adenocarcinoma, and it is sometimes a combination of the two called mixed carcinomas. The major agent causing squamous cell carcinoma is HPV 16, while adenocarcinomas correlate with HPV 18. Most cervical cancers result from a high grade squamous intraepithelial lesion (HSIL), a precancerous lesion. 

Squamous cell carcinomas begin in the cervix’s outer lining, or exocervix. Adenocarcinomas originate in the glandular cells lining the cervical canal in the endocervix, which leads to the uterus. The transformation zone is where these two types of cells meet. This is also where most cervical cancers start.  

Many women with early cervical cancer do not experience any symptoms. Signs of cervical cancer may include:

  • Spotting or light bleeding
  • Bleeding after intercourse
  • Painful intercourse 
  • Vaginal discharge
  • Back or pelvic pain

Clinical Screening and Diagnosis 

Early screenings are the best way to detect cervical precancers and cervical cancer. Prompt detection and treatment saves lives. 

 The HPV test seeks out the types of HPV infection with a greater likelihood of causing both precancers and cervical cancer. By using target and signal amplification, this test searches for bits of HPV DNA or RNA in cervical cells. The primary HPV test is used alone. It is also used in conjunction with the Pap test, and referred to as the HPV/Pap co-test. 

In most practices, the Pap test is preferred in women under age 25 and HPV testing is performed only if Pap test results were positive. With the Pap and HPV test, the doctor removes cell samples from the cervix’s surface. These samples are then reviewed by pathologists for abnormalities. 

Diagnosis is made based on a biopsy taken during a colposcopic examination by the doctor. The cells for the biopsy are obtained by cutting off small tissue samples, or by curettage. In the latter, a small instrument scrapes cells from the cervix. Options involving sedation include the electrical wire loop, which obtains a tissue sample using a small low-voltage wire, or a cone biopsy. A cone biopsy allows the doctor to retrieve tissue samples from a deeper layer of the cervix.

Tests to determine the stage of cervical cancer, which will also dictate treatment, include X-rays, MRIs, PET and CAT scans. Staging depends on how far the cancer has penetrated into the cervix, whether it has reached structures nearby or if it has spread into the lymph nodes or other organs. 

Contact Us

At Yosemite Pathology and Precision Pathology, our advanced laboratory performs immunohistochemical (IHC) markers for the complete range of clinically relevant tissue markers. Our extensively trained, highly specialized technologists are proficient with advanced IHC methods. As new IHC stains are developed, new antibodies are added regularly to our inventory. 

For more information about our services, contact us today. For over 70 years, we have advanced anatomic pathology in the Western U.S., and are now the premier provider in the region. 

Jane Meggitt’s work has appeared in dozens of publications, including USA Today, Zack’s, Financial Advisor,, The Houston Chronicle and The Nest. She is a graduate of New York University.

Cervical Cancer – Gynecology and Obstetrics – Merck Manuals Professional Edition

Cervical Adenocarcinomas: A Heterogeneous Group of Tumors With Variable Etiologies and Clinical Outcomes | Archives of Pathology & Laboratory Medicine | Allen Press

Cervical Cancer (

Precancerous conditions of the cervix – Canadian Cancer Society 

The Pathology of Cervical Precancer and Cancer and its importance in clinical practice – ScienceDirect

Cervical Cancer Screening (PDQ®)–Patient Version – National Cancer Institute