Screening for HPV Genotypes to Predict a Woman’s Risk of Cervical Cancer

In 2020, reports indicated 342,000 cervical cancer-related deaths and 604,000 new cervical cancer diagnoses occurred worldwide. Cervical cancer is the fourth most likely cancer to develop in women because of human papillomavirus (HPV) infections. If an HPV-infected woman wants to reduce her risk of developing cervical cancer, she should regularly undergo high-quality screenings.

What cervical cancer screenings are the best? People in most developing countries do not have access to high-quality cervical cancer screenings or any screenings at all. That is why the mortality rate tends to be higher in developing countries where women do not have access to quality cervical cancer screenings.

Even more economically viable countries like China offer limited access to cervical cancer screening programs. China’s coverage rate is under 30% for such programs. The primary problem is that developing countries do not have enough skilled doctors, nurse practitioners, and medical resources to provide these critical screening services to all women. And when they can offer these services, the screenings are less than adequate.

The Study

JAMA Network Open published a new study revealing that cervical cancer predictions are more accurate if the screening programs look for HPV genotypes in women with high-risk HPV infections. For example, evidence shows that some HPV genotypes can increase the risk of developing cervical cancer. But the problem is that the average cervical cancer screening program does not look for HPV genotypes to form a diagnosis.

Medical researchers from the study created a cervical cancer screening model that included a search for HPV genotypes. The study took place in Xiangyang City, China, between January 15, 2017 and February 28, 2018. It involved adult female participants ages 30 and over with more than a year of regular sexual activity. All the participants had no history of pregnancy, hysterectomy, pelvic radiation therapy, or HPV vaccinations. However, they all tested positive for high-risk HPV infections and received pelvic examinations, questionnaires, and HPV genotype testing.

The researchers collected critical personal information about each participant, such as their medical history, demographics, menstrual status, family cancer history, and sexual behavior. Participants were also subjected to visual vulva inspections, cervix speculum examinations, pelvic examinations, and internal vaginal examinations. Vaginal health was determined by the number of white blood cells and the presence of vaginal and other miscellaneous bacteria.

The Results

Approximately 314,587 adult females received the cervical cancer screening of HPV genotypes, but only 7.8% had high-risk HPV infections. Another 11% had been excluded due to dropout, while the other women were put into validation data set groups or training data set groups. Researchers used the Cobas 4800 HPV test to detect HPV genotypes, particularly HPV-16, HPV-16 Plus, HPV-18, and HPV-18 Plus.

The potential outcomes had four categories, with 1 and 2 being normal and 3 and 4 being abnormal. Based on the study results, the primary outcome was CIN3+ (cervical intraepithelial neoplasia 3 or higher), and the secondary outcome was CIN2+ or higher. Approximately 2.4% of the women had a CIN3+ diagnosis, while 4.6% received a CIN2+ diagnosis.

About 77.2% of the participants in the training set group had other high-risk HPV genotypes. The results included:

  • 8% had HPV-16
  • 2% had HPV-16 Plus
  • 5% had HPV-18
  • 6% had HPV-18 Plus

With HPV genotypes included, the predictions of CIN3+ discovered an AUROC (area under receiver operating characteristic curve) value improvement of around 35.9%. The AUROC value of CIN2+ predictions had a gain of about 41.7%.

Conclusion 

The study results showed better improvements and accuracies in cervical cancer predictions when the screening models looked for HPV genotypes. The researchers also stated that such screening models could make it easier for developing countries with fewer resources to screen women for early signs of cervical cancer.