Cervical Cancer Screening, Triage and Diagnostic Strategies
Cervical Cancer Prevention Strategies
HPV vaccination is the primary prevention method for cervical cancer.
Learn More by reading the WHO position paper on HPV vaccination.
Cervical Cancer Screening: Test Options
HPV DNA Test: Validated for primary screening1
HPV DNA screening identifies women at risk for cervical cancer with greater sensitivity than Pap (smear) cytology alone, and screening with the cobas® HPV test not only finds more high-grade disease than a Pap test alone but also helps maintain screening efficiency. The simultaneous 3-in-1 results for HPV 16, HPV 18 and the other 12 high-risk types allows HPV risk stratification as an improvement versus the higher specificity for Pap cytology.
Since its introduction in the 1940s, Pap testing has contributed to an estimated 70% decrease in the rates of cervical cancer by detecting cellular abnormalities2. However, due to Pap’s low sensitivity for the detection of precancerous cervical lesions3, highly variable results between trained professionals across different laboratories4, and poor detection of adenocarcinoma5, it has significant limitations as a long-term, global solution for identifying women at risk for cervical disease.6
HPV co-testing (primary screening with both Pap cytology and HPV test)
To improve on the low sensitivity of Pap cytology alone for cervical cancer screening, HPV co-testing is an option that relies on Pap cytology and HPV together. While this practice is shown to be superior in detecting pre-cancer and cancer of the cervix6, it is only marginally better than HPV screening on its own, and is inefficient from a cost standpoint for resource-limited countries to adopt. When HPV genotyping information is included as part of the HPV test result, women can be further risk stratified. One in 10 women positive for HPV 16 and/or HPV 18 have high-grade disease that is missed by cytology alone.7
Triage Options for Abnormal Screening Results
Biomarker or Pap cytology
HPV primary screening algorithms often include Pap cytology as an appropriate triage. However, next generation tests that rely on dual-stain biomarker technology offer significant advantages over this traditional approach. Rather than looking for cellular changes that are morphologic, and may be missed due to their subjectivity, results based on the simultaneous expression of p16 and Ki-67 in a single cell indicates more definitively and objectively that an HPV infection shows signs of oncogenic transformation.
CINtec® PLUS Cytology is an FDA approved, CE-IVD marked objective biomarker dual stain test for p16 and Ki-67. It can be used to triage positive HPV primary screening results, and helps resolve discrepant co-testing (HPV positive/Pap cytology normal), ASC-US cytology (Atypical Squamous Cells of Undetermined Significance) or LSIL (Low-grade Squamous Intraepithelial Lesion) findings. If p16 and Ki-67 are found together in the same cell, it indicates an HPV infection that is starting to transform. This information helps clinicians be certain they are recommending follow-up for only those patients who can benefit most.
CINtec® PLUS Cytology is the first approved biomarker triage test that uses dual-stain technology to simultaneously detect p16 and Ki-67, to provide a strong indicator of the presence of transforming HPV infections.
Some countries may utilize HPV genotyping to triage their Pap cytology or co-testing results. HPV genotyping information further stratifies a woman's risk, to help guide patient care decisions.
HPV genotypes 16 and 18 account for nearly 70% of all cases of cervical cancer. Focusing on these genotypes gives clinicians useful details to aid treatment decisions. HPV genotype 16 confers a higher risk of having precancerous lesions and cervical cancer than other genotypes, while HPV genotype 18 was found in 57% of cases associated with adenocarcinoma of the cervix. Atypical glandular cells, the precursor to adenocarcinoma of the cervix are more difficult to detect with Pap cytology.8
Screening Triage Options
Cervical Cancer Diagnostic Strategies: Your Options
Hematoxylin and Eosin (H&E) stain alone
Analysis of cervical biopsies using H&E or morphologic interpretation alone may lead to false-negative and false-positive results, resulting in missed disease or unnecessary referral for excisional procedures.
H&E + p16 immunohistochemistry (IHC) stain: Recommended Strategy9
Adjunctive interpretation of a p16 immunohistochemistry stain, along with the H&E, increases diagnostic agreement between pathologists. The CINtec® Histology test is the only p16 biomarker FDA cleared for clinical/IVD use in the evaluation of cervical biopsy specimens. When experts use CINtec® Histology, 23.8% more high grade cervical disease may be identified compared to H&E (hematoxylin and eosin) alone. Learn more.
Colposcopy is done when results of cervical cancer screening or triage tests show abnormal changes in the cells of the cervix, or if a woman tests positive for one of the highest risk types–HPV genotype 16 or 18. Professional guidelines from ASCCP, ASCP, and ACS suggest that women with normal cytology who are HPV 16 or HPV 18 positive be considered for immediate colposcopy.
Sometimes a biopsy is performed during colposcopy to collect tissue samples from areas that look suspicious. The diagnostic information from the cervical biopsy specimen helps drive patient care or treatment decisions. These samples are sent for laboratory analysis by a pathologist to detect cervical cancer precursors.
- Wright TC, et al. Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol. 2015;136(2):189-97.
- Solomon D, et al. Cervical cancer screening rates in the United States and the potential impact of implementation of screening guidelines. CA Cancer J Clin. 2007;57(2):105-11.
- Whitlock EP, et al. Liquid-based cytology and human papillomavirus testing to screen for cervical cancer: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2011;155(10):687-97, w214-5.
- Stoler MH, et al. Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage Study. Jama. 2001;285(11):1500-5.
- Herzog TJ, et al. Reducing the burden of glandular carcinomas of the uterine cervix. Am J Obstet Gynecol. 2007;197(6):566-71.
- Isidean SD, et al. Changes on the horizon for cervical cancer screening. Prev Med. 2017;98:1-2.
- Castle PE, Stoler MH, Wright TC Jr, Sharma A, Wright TL, Behrens CM. 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 [published online August 23, 2011]. Lancet Oncol. doi:10.1016/S1470-2045(11)70188- 7.
- Ault KA, Joura EA, Kjær SK, et al. Adenocarcinoma in situ and associated human papillomavirus type distribution observed in two clinical trials of a quadrivalent human papillomavirus vaccine. Int J Cancer. 2011;128(6):1344-1353.
- Khan MJ, Castle PE, Lorincz AT, et al. The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing in clinical practice. J Natl Cancer Inst. 2005;97(14):1072-1079.