DECADES ago, the treatment for advanced cervical cancer (where abnormal cells in the cervix grow uncontrollably) was radiation.
Then came clinical trials that showed that adding low-dose chemotherapy during radiation therapy (chemoradiation) improved survival outcomes. It became the gold standard worldwide for treating this cancer.
Fast forward to the present, and researchers are now developing the next paradigm for its treatment – incorporating immunotherapy.
The immune system recognises the human papillomavirus (HPV), which causes cervical cancer, as foreign to us, said Dr John Chia Whay Kuang, Visiting Consultant, Department of Medical Oncology, National Cancer Centre Singapore (NCCS).
“Preliminary data from earlier clinical trials indicate that cervical cancer responds to immunotherapy which blocks the cancer.
“Efforts are now underway to incorporate immunotherapy earlier in the treatment of cervical cancer. It’s a nasty disease. Half the patients at stage 3B relapse and succumb to their cancer. Doctors really need to do more to bring the field forward and improve the cure rate,” said Dr Chia.
A worldwide clinical drug trial is now being done to explore the use of a compound, Z-100, in combination with standard chemoradiation therapy for six weeks on stage 3B cervical cancer patients. The Phase 3 trial involves about 500 patients, 20 of whom are from three centres in Singapore, including NCCS.
“Results from an earlier Z-100 study in Japan, of patients with stage 3B locally advanced cervical cancer, were encouraging. The current study is to validate the earlier results,” said Dr Chia, who is a lead investigator in the Singapore trial.
He said Z-100 helps the immune system recognise and kill cancers. It also helps the body “remember” the cancer, so that if it encounters it again, it will kill it more efficiently.
This immunological “memory” is similar to what the immune system naturally activates against viral infections such as measles. The memory is lifelong, but cancer can subvert the immune system.
Incorporating immunotherapy into standard radiation therapy appears to be highly synergistic, and may overcome many barriers the cancer has against the immune system.
“Developing immunological memory is associated with much better survival because if there are tiny cancer ‘seeds’ elsewhere in the body, outside the field of radiotherapy, the immune system will destroy them. We anticipate that this will translate into improved cure rates.”
Immunotherapy is now a major new wave and the fourth pillar of cancer treatment after surgery, radiation and chemotherapy. It’s already been shown to work better than chemotherapy in selected types of lung, kidney and skin cancers, Dr Chia said. “There are about 800 immunotherapy clinical trials ongoing worldwide, exploring immunotherapy as a single agent or in combination with other drugs, for every imaginable tumour type. It’s become the holy grail of cancer therapy. The immune system is selective, and it’s always with you. We need to learn how to use it optimally with other cancer therapies, and how to make immunotherapy more potent and work better.”
Cervical cancer is the second most common cancer in Singapore women, with about 200 new cases diagnosed a year. Stage 1 can be managed with surgery or radiation therapy, with about 70 to 80 per cent of women being cured (defined as remaining cancer-free for at least 10 years). Stage 2B and above are treated with chemoradiotherapy, but survival rates in the advanced stages are more limited, unfortunately.
“Standard treatment paradigms for the disease haven’t changed for the past 20 years. We’re excited to be pushing and developing the field. One thing’s for sure – we need to do better,” Dr Chia said.
Vaccines can prevent it
Vaccines that can prevent infection by the human papillomavirus (HPV), which causes cervical cancer, have been available locally for several years.
“The vaccines are more than 90 per cent effective, but need to be given before an individual becomes sexually active. Parents can and should do more to bring their children for vaccination. It’s a preventable disease,” said Dr Chia. The HPV infection is spread by sexual contact. In most cases, an infection is cleared by the immune system, but it sometimes persists and causes genital warts or cervical cancer.
Cervical cancer is also relatively unique among cancers because it can be picked up by a PAP smear while still in a “pre-cancerous” stage.
Simple intervention or surgery can then get rid of the lesions, and prevent the cancer from developing.
Symptoms include abnormal bleeding (between periods, after sex or after menopause), pain during sex, or abnormal vaginal discharge. Women with symptoms should have regular PAP smears and consult a doctor to catch the cancer in its early stages.
“Vaccination and screening are highly effective. Every new patient diagnosed represents a failure – of our profession, our knowledge systems, our will and our culture. It is a huge disappointment, because the disease is so preventable,” said Dr Chia.
• This story was first published in Singapore Health, May-Jun 2017 issue.