A recently published study has compared a new surgical method, called cancer field surgery (Total Mesometrial Resection, TMMR), with the current standard treatment for primary management of cervical cancer.
The new TMMR method was developed over 20 years ago by Karolinska Institutet’s partners at the Leipzig University Hospital. Previous publications have suggested favourable results without the need for radiation therapy. Omitting radiation therapy could potentially improve quality of life for treated women.
In the study, the researchers demonstrate that TMMR is associated with improved oncological outcomes for early stages of cervical cancer. The data suggest that TMMR may replace current treatment strategies and radiation therapy could be spared for salvage treatment. This breakthrough motivates continued work in this field.
Research of this kind heavily relies on well-functioning collaborations with other researchers. Beyond providing essential data for the project, it also strengthens international cooperation, facilitating the dissemination of our findings. The researchers plan to further explore the potential of cancer field surgery in gynaecological cancer to establish the method in future treatment strategies.
Researchers have developed a simpler and more effective screening method for cervical cancer than the method used today. A comprehensive study published in Nature Medicine shows that the test detects significantly more cancers and precancerous stages.
Most countries have a very extensive cervical cancer screening program that starts with testing for different variants of the human papillomavirus (HPV) that causes cervical cancer. In the case of an HPV-positive test, this is followed by cytological analysis, the examination of gynaecological cell samples by microscopy, which is dependent on human interpretation.
The new molecular test WID-qCIN, which could replace the cytological analysis, can automatically analyse epigenetic changes in cells. These changes, where genes are switched on or off, are influenced by factors such as environment, lifestyle, and aging, and can increase the risk of cancer and other diseases.
Fewer invasive procedures
The current study by researchers at Karolinska Institutet and the University of Innsbruck included more than 28 000 women over the age of 30 who underwent screening in Stockholm between January and March 2017. The researchers analysed a total of 2377 HPV-positive samples with the WID-qCIN test combined with a test for two high-risk HPV types (HPV 16 and 18). In this way, they were able to detect 100% of all invasive cervical cancer and 93% of all serious precancerous lesions that occurred within a year of sampling.
In addition, the new test, in combination with the HPV 16/18 test, was able to predict 69% of all cancers and precancerous lesions up to six years after the sample was taken. This can be compared with only 18% with today’s screening method.
“By integrating the WID-qCIN test into our screening programs, we would be able to identify more cancer cases while reducing the need for invasive procedures,” says Joakim Dillner, Professor of Infectious Disease Epidemiology at Karolinska Institutet and co-author of the study.
A significant improvement
When cell changes are detected in today’s screening program, the woman undergoes a vaginal examination, a so-called colposcopy, where the gynaecologist looks at the cervix with the help of a microscope and, if necessary, takes a biopsy. The biopsy involves a surgical procedure that, among other things, can lead to negative pregnancy outcomes like premature delivery. The results of the current study suggest that implementation of the WID-qCIN test could reduce the number of colposcopy examinations by 40%.
“This would mean a significant improvement compared to today’s screening methods, which were introduced in the 1960s,” says the study’s last author Martin Widschwendter, Professor at the University of Innsbruck (Austria) and visiting Professor at Karolinska Institutet. “With its simplicity and objective assessment, the WID-qCIN test can improve the effectiveness of these programs and support the global strategy to eliminate cervical cancer.”
Minimally invasive hysterectomy for patients with early cervical cancer resulted in significantly worse outcomes compared with open surgery, according a clinical trial’s final analysis, a result which confirmed initial findings.
The Laparoscopic Approach to Cervical Cancer (LACC) trial compared disease-free survival (DFS) and overall survival (OS) at 4.5-year follow-up from the initial 631 patients who were randomised to open surgery or to MIS.
In the intention-to-treat population, DFS at 4.5 years – the study’s primary outcome – was 96.0% with the open surgery approach versus 85.0% with minimally invasive surgery (MIS), with similar DFS rates of 97.3% and 86.0% in the per-protocol analysis, reported Pedro T. Ramirez, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“When we presented the data in 2018, the recurrence rate for MIS was four times higher than for open surgery,” Dr Ramirez said at the Society of Gynecologic Oncology annual meeting. “And after completion of 4.5 years follow-up on all of the patients, it still remains the same.”
Since the initial publication of his team’s findings in 2018, said Dr Ramirez, national and international guidelines have changed their recommendations and now consider open radical hysterectomy as the new standard approach for patients with early cervical cancer. This final analysis confirms that patients with early cervical cancer “should not undergo the minimally invasive approach outside of a clinical trial,” he said.
DFS events occurred in 43 patients in the MIS arm versus 11 patients in the open surgery arm/ Additionally, the MIS arm patients had worse disease-specific survival, cumulative local/regional recurrence and overall survival.
Researchers also found that progression-free survival (PFS) was worse for MIS compared with open surgery, with 48 patients in the MIS arm experiencing events compared with 12 in the open surgery arm, consistent with the 2018 findings.
Since the initial publication of his team’s findings in 2018, said Dr Ramirez, national and international guidelines have altered their recommendationsand now consider open radical hysterectomy as the new standard approach for patients with early cervical cancer. This final analysis confirms that patients with early cervical cancer “should not undergo the minimally invasive approach outside of a clinical trial,” he said.
The researchers also assessed outcomes by tumour size, conisation status, and carcinomatosis rates.
They found that 21% of MIS patients with tumours ≥ 2 cm had DFS events compared with about 5% of patients who had open surgery (HR 4.25).
Dr Ramirez emphasised that while the trial was not designed to answer the question of the effect of tumour size on surgical outcomes, “this highlights the fact that for larger tumours, there is clearly a disadvantage to minimally invasive surgery in terms of the difference in recurrence events.”
As for tumours less than 2 cm, the investigators found that no DFS events occurred among 65 patients who underwent open surgery versus seven DFS events among 75 MIS patients.
“It is important to highlight this because comments have been made that if patients have tumours less than 2cm, then perhaps it is appropriate to proceed with minimally invasive surgery,” Dr Ramirez pointed out.
Among those patients who did not have previous conisation, there were worse outcomes for those who underwent MIS. Among patients who did have a previous cone, there was no difference between the two arms.
When there were recurrences in the open surgery arm, no patients manifested with carcinomatosis versus 24% of patients in the MIS arm.
Researchers have made advances in improving detection of the human papillomavirus (HPV) in the bloodstream, which could further hone precision treatment of the illness.
The team sequenced circulating tumour DNA, which can lead to the detection of HPV in a person’s blood. Previous science in the field has proven that the virus, which causes cancers in the throat, mouth, and genital areas, can be found in the bloodstream but tests have had limited sensitivity. The new study enables ‘ultrasensitive’ detection, which could pave the way toward greater use of precision medicine for patients with cancers affecting these vulnerable areas of the body.
In a cohort of patients with advanced cervix cancer, the new sequencing method detected 20-fold lower levels of HPV circulating tumour DNA, making it a promising new method to monitor the disease.
The results come from the laboratory of Senior Scientist Dr Scott Bratman at Princess Margaret Cancer Center and are published in Clinical Cancer Research. “Increasingly, as clinicians we’re focused on precision medicine and making sure we’re not over-treating people while still curing them, that’s a very difficult balance to strike,” Dr Bratman said.
One way is to use liquid biopsy approaches or blood-based biomarkers, such as circulating tumour DNA, in order to monitor how the treatment is progressing, he added.
“We’re really at the cusp of a revolution from a technology, clinical implementation and standard of care standpoint, where five to 10 years from now we will not be treating everybody with the same dose of radiation and chemotherapy, and then waiting months to see if the treatment was effective,” he said. “I’m confident we will be giving much more tailored doses.”
When physicians scale back on these treatments, there is a risk of the cancer reoccurring. With more sensitive tests, reoccurrences can be detected early and patients returned to treatment.
“Patients who need more treatment will then be able to continue on, or different treatments can be added,” Dr Bratman said. “We can spare the vast majority of patients who will not need those interventions and provided them with a greater quality of life once they’re cured of the cancer.”
The work will enable further study in the field, refining the approach using larger study groups, and eventually, practice-changing clinical trials. This technique could also be applied to other cancer-causing viruses such as certain types of stomach cancer and lymphomas.
Cervical cancer incidence and mortality rates are holding steady or falling in most countries across the globe, according to a new analysis. Each country’s socioeconomic development level, cervical cancer screening use, and human papillomavirus (HPV) vaccination rates affect the rates. The findings are published online in CANCER.
Cervical cancer can be potentially prevented through screening for and treatment of precancerous lesions and through HPV vaccination. A team led by Mingjuan Jin, PhD, of the Zhejiang University School of Medicine in China, examined information on 31 countries released by the International Agency for Research on Cancer.
The analysis found that cervical cancer incidence and mortality rates were lower in more socioeconomically developed countries. Also, both past and predicted trends appear to be stable or decreasing in most countries, especially in those with effective cervical cancer screening and HPV vaccination programs.
Over the past decade, 12 countries had stable cervical cancer incidence rates, while rates fell in 14 and rose in five. Twelve countries had stable mortality rates from cervical cancer, with falling rates in 18 and only one had an increased rate.
The researchers predicted that for 27 countries, most are expected to have stable or decreasing trends over the next 15 years. Ten of the 27 countries are predicted to have stable incidence rates, nine to have decreasing rates, and eight to have increasing rates. Mortality rates are predicted to be stable in 16, decreasing in 10 and one to have an increasing rate.
“Effective cervical cancer screening programs and HPV vaccination should be further popularized to increase their coverage and ultimately decrease cervical cancer’s short-, mid-, and long-term burden,” said Dr Jin.
