group of women

New hope for cervical cancer patients

Cervical cancer still strikes some 14,000 women each year in the U.S. Recently, two promising immunotherapies were FDA approved to treat the disease, and there have been innovations in radiation and surgery as well

When Luzmila Salazar learned she had cervical cancer, she felt like her life was crumbling around her.

“It was the worst thing I’d ever heard,” said the 43-year-old mother of three. “I thought about my kids. And all I could ask was, ‘How long do I have?’”

It was a tough blow for Salazar, an upbeat person whose career centers on making people happy. Salazar works for Helm and Sons, a Southern California company that supplies amusement rides and attractions, like rollercoasters and Ferris wheels, to county fairs and similar venues. “Seeing those smiling kids is the best reward,” she said.

The job requires quite a bit of travel, and it was during her time on the road that Salazar first noticed some unusual bleeding. She dismissed it, but a few weeks later the problem intensified, and Salazar knew something was wrong. Her doctors administered several Pap tests, which pointed to possible cancer. They referred her to City of Hope, a place she’d never heard of.

Stephen J. Lee
Stephen J. Lee, M.D.

Cervical cancer still strikes some 14,000 women each year in the U.S., despite the fact that, since 2006, an effective vaccine has been available to stop the primary cause: HPV, the sexually transmitted human papillomavirus. The vaccine is most effective when given to children ages 9 and up, and in countries where it is routinely administered, like Australia, cervical cancer rates have been dropping. Although vaccination rates are lower in the U.S. and cervical cancer persists, a recent study by the American Cancer Society noted a significant decline in the number of American women who contracted cervical cancer between 2012 and 2019. 

Among women in their 20s, cervical cancer incidence dropped 65% over this period, the data showed. Because this age group of women were the first cohort to receive the HPV vaccine after it was approved, this is a data point that “foreshadows steep reductions in the burden of human papillomavirus-associated cancers, the majority of which occur in women,” the study says.

However, “We really shouldn’t have any cervical cancer,” lamented gynecological oncologist Stephen J. Lee, M.D. “It’s a preventable disease.”

Remarkable Immunotherapies

But cervical cancer is also a very treatable disease, with survival rates that can top 90% when caught early. Even better, patients today have new options that weren’t available a generation ago.

“The landscape is changing,” said gynecological surgeon Ana Isabel Tergas, M.D., M.P.H. “Before, there wasn’t all that much hope” for late-stage patients. “Now, I can tell patients who don’t respond to one treatment that many others are coming.”

Ana Tergas
Ana Tergas, M.D., M.P.H.

Much of the excitement is focused on immunotherapy, a new class of drug that induces the body’s immune system to destroy cancer cells. Leading the charge are treatments called monoclonal antibodies, based on a technology pioneered by Arthur Riggs, Ph.D., the late City of Hope researcher.

Most notably, the Food and Drug Administration recently approved the use of pembrolizumab (known commercially as Keytruda) in combination with chemotherapy as a first line treatment for persistent, recurrent or metastatic cervical cancer, the toughest cases to treat. 

Pembrolizumab is a so-called checkpoint inhibitor that targets the PD-L1 protein in some tumors. “PD-L1 is a protein that acts Aas the ‘brakes’ to the immune system, which cancer cells can exploit to avoid attack,” explained Lee. “This drug takes the brakes off the immune system to help fight against cancer cells.”

In fact, immunotherapy drugs may be perfectly suited for this particular malignancy.

“Cervical cancer lends itself to treatment by immunotherapy,” added Tergas, “because it’s caused by an infection.”

Edward Wenge Wang
Edward Wenge Wang, M.D., Ph.D.

Another recently approved treatment is based on a monoclonal antibody called tisotumab (commercial name: Tivdak). It battles cervical cancer in an entirely new way. 

“Tivdak is a tissue factor-directed antibody that carries a powerful chemo drug,” explained oncologist Edward Wenge Wang, M.D., Ph.D. Working like a “smart” bomb, Tivdak seeks out cancer cells in the body, enters those cells and releases its chemotherapy payload, destroying them. “It’s a really good advance.”

On the horizon, excitement is building for a true “Star Wars”-type treatment involving the manipulation of tumor-infiltrating lymphocytes. These are immune cells found inside the tumor, but too few in number to crush the malignancy. This new system harvests those lymphocytes, subjects them to a process that makes them reproduce rapidly, then reintroduces the now-large load of cancer-fighting cells back into the tumor. “Some of the early evidence has been tremendous,” Tergas said.

Many experts believe that immunotherapy may one day reduce the need for surgery, radiation and chemotherapy, currently the three pillars of cervical cancer treatment. In the meantime, even in those so-called “conventional” areas, progress is being made.

New Options for Radiation

Salazar, whose cancer was diagnosed as Stage 1B — a relatively early stage — was treated in multiple ways. First, Lee performed a radical hysterectomy — removing the uterus, cervix and some surrounding tissue. This was followed up with chemoradiation: low-dose chemotherapy administered once a week for five weeks, combined with 25 consecutive days of radiation. The lower chemotherapy dosage causes fewer side effects, while it enhances the effectiveness of the radiation.

Scott Glaser
Scott Glaser, M.D.

Salazar benefited from recent advances in radiation technology. Today’s external beam machines (or linear accelerators) rotate around the patient as multiple imaging systems and computer-generated algorithms precisely deliver the radiation exactly where it’s needed while sparing surrounding healthy tissue. The latest generation of this system is known as volumetric modulated arc therapy, or VMAT. 

“With VMAT,” explained radiation oncologist Scott Glaser, M.D., “the shape, strength and angle of the radiation keep changing as the machine rotates, providing the best possible combination.”

Beyond external beam machines, Glaser, chief of brachytherapy and gynecological radiotherapy, is also excited about radiation options that work inside of the patient. One, known as guided adaptive brachytherapy, delivers custom radiation doses directly into the tumor through an inserted tube, positioned with help from computed tomography and magnetic resonance imaging scans. 

Another option, the most modern, is a hybrid system Glaser brought to City of Hope, known as intracavity/interstitial brachytherapy. It uses a series of implanted needles to precisely deliver high-dose radiation.

Surgical Developments

When it comes to surgery, progress has been slower, although there is hope for improvement.

For many cancers, minimally invasive laparoscopic and robot-assisted surgeries have become popular because they can remove cancer just as effectively as older, “open” procedures, but do so with smaller incisions, causing less pain and trauma for patients, who can often go home the next day.

'Cervical cancer lends itself to treatment by immunotherapy, because it’s caused by an infection.'

Ana Tergas, M.D., M.P.H.

It’s a different story with cervical cancer. Minimally invasive procedures have not delivered satisfactory cancer-removing results. In fact, one study claimed such procedures may be as much as three times worse than open surgery when measuring recurrence and survival rates.

But now there’s an effort to find out why this is the case and to come up with a better way.

Some believe the fault lies with an instrument known as a manipulator, used in robotic procedures to move the cervix. This device may be spreading stray cancer cells to other parts of the body.

A multicenter trial is underway that performs the procedure without a manipulator, and also seals off the area being treated so that malignant cells cannot spread beyond it. The study is scheduled for completion in 2029.

Prevention Remains Key

Ultimately, the best treatment for cervical cancer is prevention. The HPV vaccine plays a critical role, to be sure. But just as important, if not more so, is the need for regular screenings and Pap tests, which can catch cancer at its earliest stages and even detect the presence of abnormal cells (a condition known as dysplasia), which can be removed before they become cancerous.

It all worked out well for Salazar. Three years after treatment, her cancer has not returned. She’s grateful to her multidisciplinary team at City of Hope, and she appreciates the unique atmosphere that permeates the institution.

“I gained hope there,” said Salazar. “It’s a home where your doctors are like your family. They absolutely care about you, and you’ll feel safe there.

“Yes, it was a long, hard process to go through. But I’m here!”