Advanced screening and diagnostic tests are key to improving disease prevention strategies
Cervical cancer is one of the most preventable cancers today, thanks to vaccination, screening and early treatment. Still, cervical cancer remains one of the most common and deadliest cancers in women worldwide. Approximately 570,000 women are diagnosed with cervical cancer each year.1
Almost all cervical cancers – more than 99% – are caused by a persistent high-risk human papillomavirus (HPV) infection.2 Finding and treating pre-cancerous disease early, before cancer develops, is an important prevention strategy.2
In 2020, member states of the World Health Organization (WHO) addressed this public health challenge, adopting specific goals calling for the elimination of cervical cancer, including targets for HPV vaccination, screening and treatment. In order to meet these goals, countries – especially those with the highest disease burden – must take action now.
For many decades, the Pap test was the standard for screening cervical cancer. The Papanicolaou test (also known as Pap smear) was invented in the 1940s by Dr. George Papanicolaou, who noticed the relationship between abnormal cervical cells and subsequent development of invasive cancer. During the test, a healthcare professional uses special tools to collect cells from the surface of the cervix, which are sent to a laboratory for analysis.
Cervical cancer rates have decreased by as much as 65% over the past four decades in countries with established screening programs.3 But as a first-line primary screening test, it has limitations due, in part, to the subjective interpretation of the test and its relatively low sensitivity.4,5
With today’s technologies, we can do better. In fact, many countries are already working with medical societies and Ministries of Health to implement updated guidelines that emphasize HPV tests as a replacement to Pap cytology for first-line screening.
During the 1980s, a link between HPV and cervical cancer was identified, and in 1996 the World Health Organization publicly recognised that HPV is the most important risk factor in the development of cervical cancer.
HPV is a common virus; approximately 80% of women (and men) will have had an HPV infection by age 50.6 There are more than 200 types of HPV.7 Some types carry more risk than others. In fact, 70% of cervical cancer cases are caused by two specific genotypes—HPV 16 and 18.8 Not all women who become infected with HPV will develop cervical pre-cancer or cancer.3 The vast majority of HPV infections are transient and are taken care of by the immune system without a long-term impact on health. However, in some women the infection becomes persistent and over time may lead to cervical disease and eventually cancer, if left untreated.7
Improving cervical cancer screening, with a focus on the science of HPV allows us to find innovative solutions to the problem, bringing new triage and diagnostic test options. Primary HPV testing every 5 years is more effective than Pap cytology alone for cervical cancer prevention, and more efficient than co-testing, reducing the number of tests while providing comparable outcomes.2
The 2020 Guidelines of the American Cancer Society recommend cervical cancer screening with the HPV test every five years for women aged 25-65 as a preferred approach over Pap testing and combination Pap and HPV testing.2 These guidelines reflect the rapidly-changing landscape of cervical cancer prevention in the United States and around the world, focusing on better outcomes, test efficiency and more simplified screening.2
Modern cervical screening now includes an HPV DNA test, using the same type of sample as collected for Pap cytology. Women can now be tested for the presence of high-risk HPV.
In an analysis of more than 60,000 women, high-risk HPV testing was substantially more sensitive in detecting cervical disease than Pap tests (96.1% vs. 53.0%), a finding later confirmed by a study that included more than 47,000 women.9,10
While there is no cure for an HPV infection, it is possible to stop disease progression and treat pre-cancer or cancer. A woman positive for high-risk HPV will need to be managed according to recommended clinical guidelines. A woman who tests negative for high-risk HPV can be confidently reassured that she has a very low risk of developing cervical cancer before the next round of screening.2
For women who test positive for one of the high risk types of HPV, next step decisions need to be made. The latest evolution in cytology as a triage test, based on biomarker technology, offers significant improvements over traditional Pap cytology, to identify women at risk, and to find and treat precancer before it develops into more serious disease.11
In cytology, a trained technician looks for abnormalities within the cells that are caused by an HPV infection, an indicator of risk for disease progression (co-testing or triage). Abnormal cells can be difficult to differentiate from normal cells using traditional microscopic staining techniques such as the Pap test.
New biomarker tests, which look for the presence of p16 and Ki-67 in a single cell, significantly enhance the cytology process. The co-expression of biomarkers p16 and Ki-67 indicates an abnormality that provides definitive information to help differentiate which HPV positive women are at highest risk, and may benefit most from immediate follow-up.12 Women who test dual-stain negative for p16 and Ki-67 and show no signs of cellular oncogenic transformation can be given more time to allow their body to clear the virus.13 These women can return for repeat testing according to their clinician’s recommendations.
This biomarker test is more sensitive and can more accurately identify women who may have pre-cancer than standard cytology.12 Based on our understanding of the underlying science and biology of HPV infections, this test identifies those women who have HPV infections that may transform infected cells to cancer cells. This improves the ability of pathologists to diagnose cervical disease and clinicians to make treatment decisions.
The test is conducted on cervical cells from the same vial that is used for the initial HPV and Pap cytology testing. Women who test positive for these biomarkers would benefit the most from immediate intervention like colposcopy, while women who test negative are at low risk for developing cervical disease and can be given that assurance confidently.11
This test can reduce the risk of cervical cancer or precancer going undetected and at the same time help making the use of colposcopy as efficient as possible, decreasing healthcare costs and the potential adverse effects of the colposcopy procedure.11
For women who have colposcopies, a diagnostic confirmation test uses advanced biomarker technology to confirm the presence or absence of precancerous lesions can improve the ability of pathologists to diagnose cervical disease and clinicians to make treatment decisions.
By accurately identifying all women at risk of developing cervical cancer with HPV screening and differentiating those who need intervention or treatment from those who do not using biomarker tests, it is possible to spare women from developing a preventable cancer and limit the risks of overtreatment.
“The widespread implementation of advanced screening and diagnostic solutions that address previous limitations is extremely powerful in the fight against cervical cancer,” said Dr. Ed Baker, Roche Cervical Cancer Solutions Senior Director of Medical Affairs, Roche Diagnostics. “We have the potential to find women earlier who are at risk of cervical pre-cancer or cancer to make sure disease does not go undetected.” This, he said, will also help minimise the number of patients who receive unnecessary procedures.
“Roche remains deeply committed to safeguarding and improving the health of women.” he said. “We will continue to focus our people and resources on the detection and early intervention of pre-cancerous cervical disease. We share with the global healthcare community the goal of saving lives and preventing unnecessary treatment and worry.”
Fontham, et al. Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society. Ca Cancer J Clin. 2020;70(5):321–46.
Stoler, et al, Group for the ASC of USSILTS (ALTS). Interobserver Reproducibility of Cervical Cytologic and Histologic Interpretations: Realistic Estimates From the ASCUS-LSIL Triage Study. Jama. 2001;285(11):1500–5.
Perkins, et al. 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors. J Low Genit Tract Di. 2020;24(2):102–31.
Chesson, et al. The Estimated Lifetime Probability of Acquiring Human Papillomavirus in the United States. Sex Transm Dis. 2014;41(11):660–4.
Burd, et al. Human Papillomavirus and Cervical Cancer. Clin Microbiol Rev. 2003;16(1):1–17.
Sanjose, et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010;11(11):1048–56.
Cuzick, et al. Overview of the European and North American studies on HPV testing in primary cervical cancer screening. Int J Cancer. 2006;119(5):1095–101.
Castle, et al. Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study. Lancet Oncol. 2011;12(9):880–90.
Wentzensen, et al. Clinical Evaluation of Human Papillomavirus Screening With p16/Ki-67 Dual Stain Triage in a Large Organized Cervical Cancer Screening Program. Jama Intern Med. 2019;179(7):881–8.
CINtec PLUS Cytology Package Insert, Roche Diagnostics, 2020.
Clarke MA, et al. Five-Year Risk of Cervical Precancer Following p16/Ki-67 Dual-Stain Triage of HPV-Positive Women. JAMA oncology. 2019;5(2):181-6.