The seventh annual Chinese Society for Colposcopy and Cervical Pathology took place in Beijing, China from May 14-16. The theme for this convention is ‘Rapidly Eliminate Cervical Cancer-Operation China’, academics and professionals from all over the world sit down to discuss hot topic questions about cervical cancer screening, HPV vaccine, and cervical cancer treatment, etc. A total of six sub-forums were broadly discussed along with remarkable reports.
A special seminar was hosted by Professor Mingrong Xi from West China Second Hospital of Sichuan University and Professor Youlin Qiao from Cancer Hospital of the Chinese Academy of Medical Sciences on the 15th, discussing ‘The application value and data sharing of HPV expanded genotyping’ which explores the [China Mode] of comprehensive cervical cancer prevention. This advocates innovative strategic concepts and plans with rich and accurate details that have attracted widespread attention.
Strategy for speeding up cervical cancer elimination – An important component in cervical cancer screening is HPV detection
First of all, prof. Xi introduced the grim status quo of cervical cancer. There are nearly 570,000 new cases and 310,000 deaths worldwide, making it the second most malignant tumor in women aged 15-44 just after breast cancer.
In 2018, WHO called on all countries to take action to eliminate cervical cancer; In 2020, the global strategy to accelerate the elimination of cervical cancer was again proposed, which marked the first time that 194 countries around the world pledged to eliminate a type of cancer. To realize this target, HPV screening makes up one of the most important components of cervical cancer screening. Professor Xi reviewed the history of cervical cancer screening, starting from the Atypical Squamous Cells of Undetermined Significance (ASCUS) HPV testing, to the high-risk HPV 16/18 testing, and onto the approved application of HPV expanded genotyping in 2018.
Overseas HPV testing method for preliminary cervical cancer screening
From HR-HPV 16/18 typing to HPV expanded typing
Next, professor Xi shared the 2015 American ASCCP/SGO transition period guide, clarifying HR-HPV types 16/18 can be used for preliminary cervical cancer screening. The most recent large-scale study on the 14 high-risk HPV types for ≥CIN2+ showed that HPV types 31, 52, 33/58 can also be high-risk types; HPV 16/31 are the highest-risk types and the most common infectious types; HPV31 positive should also be referred for colposcopy. HPV types 18, 33/58, 52 are also high-risk types and HR-HPV extended typing is a more effective risk stratification strategy.
National strategy for HPV testing in cervical cancer screening
How to achieve a more precise risk management system
How to choose HPV testing products
How to select HPV testing products and realize precise risk stratification in national cervical cancer screening? When introducing the NMPA review guidelines published in November 2015, Professor Xi pointed out that clinical trials are needed to determine the clinical significance of HPV testing products, if there are no clinical trials conducted, then the product should include a declaration such as ‘This product cannot be used for relevant clinical use as there is no relevant verification’. Clinical use includes preliminary cervical cancer screening, ASCUS triage, and cervical cancer joint screening. Tellgen Corporation’s HR-HPV types 2+12 (HPV 16, 18+12 other HR-HPV types) and HPV5+9 (HPV 16, 52, 58, 33, 18 + 9 other HR-HPV types) testing products have already begun relevant trials.
Features of HPV infectious disease in China
According to the 2018 ICO relevant disease report, besides the prevalent HPV 16/18 type, HPV 58, 52, and 33 is the top five types in Asia and China cervical cancer, which is significantly higher than global levels, making it the main five infectious types in the different grades of cervical cancer lesions in China.
Referring to this particular feature of China’s HPV infections, when focusing on HPV 16/18 types, we also need to pay close attention to extended HPV 58, 52, and 33 types. Changes have been made to HPV 2+12 testing to HPV5+9, which is more suited for China’s HPV testing. HPV 5+9 testing can realize testing for China’s main HR-HPV types 16, 18, 33, 52, and 58, as well as another joint testing for the other 9 HR-HPV types, making HPV-type risk stratification more accurate and precise. The rate of detection of HPV types 16/18 is 44% in ≥CIN2+; 70% in cervical cancer, when extended HPV types 58/52/33 are added to detection, the rate of detection increased to 84% and 90% respectively.
Extended HPV types 16/18/33/58/52 detection recommendation
In contrast to the HR-HPV types 16/18 testing (HPV 2+12), HR-HPV 16/18/33/58/52 extended testing (HPV5+9) is more suited for China’s precise cervical cancer screening strategy. It has shown favorable performance in large-scale preliminary cervical cancer screening and ASCUS triage clinical trials.
Results from preliminary HPV 5+9 cervical cancer screening show infectious HR-HPV types 52/58/33 are more commonly seen than HR-HPV type 18; the individual and joint infectious rate of these 5 HR-HPV types is 67.3%, which is significantly higher than HR-HPV 16/18 (27.5%). In comparison to other positive HPV types, there is a higher risk of HR-HPV types 16, 18, 33, 58, 52 developing into≥CIN2+. These 5 HR-HPV types illustrate the significance and therefore a follow-up colposcopy is necessary. Furthermore, the chances of HPV 5+9 negative individuals have an absolute low risk of developing into ≥CIN2+ (0.001), proving this negative result has protective properties towards individuals, making it a higher negative predicted value (>99%).
When comparing the HPV 5+9 screening method to the HPV 2+12 screening method, HPV 5+9 is also an effective and powerful ASCUS triage strategy, its sensitivity (65.5% vs. 93.1%) and negative predictive value (97.1% vs. 99.3%) has huge improvements.
In the post-vaccination era of cervical cancer screening, HPV extended types
Studies show that as the bivalent vaccine is delivered, the infection rates of HR-HPV types 16/18 reduced, however, other HR-HPV types infection rates increased. Thus the best screening option is no longer limited to screening for HR-HPV types 16/18. Precise extended HR-HPV types screening might become the upcoming strategy for preliminary HPV screening as it can realize HPV risk stratification.
Professor Xi concluded that the extended HPV 5+9 screening is a more precise method for cervical cancer screening as it is based on China’s infectious disease characteristics, making it the [China’s mode] of complementary cervical cancer prevention and treatment.
Last but not least, professor Qiao commented that Tellgen Corporation’s extended HPV 5+9 testing kit is by far the newest, most innovative, and meaningful cervical cancer screening method on the market as no other products use this method to genotype HPV.