Rare Cervical Cancer Requires Innovative Approach

When a rare cervical cancer struck visual artist Krista Machovina, her care team from USC Verdugo Hills Hospital needed to write a new playbook.

Krista Machovina figured that one bout with cancer was more than enough. Having survived thyroid cancer in her twenties, the Los Angeles-based studio artist figured that by the summer of 2020, she’d met her cancer quota.

But life sometimes operates by a different accounting scheme. So, when the stomach pains that hit Krista that August turned out to be cervical cancer, “I thought, ‘Are you kidding me?’” she says. “‘Did I not learn the lessons the first time? Why am I here again?’”

Making matters worse, she continues, “This one was really scary.” Indeed, her cervical cancer was so rare and aggressive that the medical field hadn’t yet established a standard for its treatment.

Rare form of cervical cancer

Krista was already a Keck Medicine patient at the time of her diagnosis, and when the decision came to refer her to a specialist, her physician sent her to Marcia Ciccone, MD, a Keck Medicine gynecologic oncologist who practices at USC Verdugo Hills Hospital.

It didn’t take Dr. Ciccone long to realize that she had a tough case on her hands.

“Most cervical cancer is caused by HPV, or human papilloma virus,” Dr. Ciccone says. “But Krista’s cervical cancer was not.”

In fact, the cells in Krista’s tumor exhibited a completely different histology, or cell structure, than those of HPV-related cervical tumors. “When you looked at Krista’s tumor under the microscope,” Dr. Ciccone says, “it actually had these little ‘signet rings’ on the cells that made them look like the cells in gastric tumors that secrete mucin.”

This morphology characterizes what’s known as primary signet ring cell carcinoma of the cervix (PSRCCR), a very rare cervical cancer that microscopically resembles gastric tumors — but that also has a poor prognosis and a record of resistance to standard cancer treatments like chemotherapy and radiation.

To put the cancer’s rarity into perspective, consider that the American Cancer Society’s estimate for the number of US patients diagnosed with invasive cervical cancer in 2024 was 13,820; meanwhile, the largest case series on Krista’s cancer at the time topped out at 23 cases.

So if Dr. Ciccone was hoping to base Krista’s treatment on past precedent, she’d have to pivot. “Unfortunately,” she says, “there aren’t enough patients or data out there to say what you should or shouldn’t do.”

That left Dr. Ciccone with a conundrum: Krista had a diagnosed cervical cancer, but one that neither looked nor responded to treatment like one.

Yet within that conundrum, Dr. Ciccone also saw a hint at a solution. As she puts it, “Maybe histology matters when you’re talking about how a cancer will behave. So if this looks like a gastric cancer, maybe it behaves like a gastric cancer, responds like one — and maybe we shouldn’t treat it like a cervical cancer.”

Protocol for treating unconventional cancer

In the absence of time-tested options, Dr. Ciccone hastens to add, “I didn’t make any decisions in a vacuum.” Being part of an academic health system like Keck Medicine, she didn’t have to.

As Dr. Ciccone explains, “When a patient presents with something rare, you want to compile the knowledge and experience of all the minds you have access to.”

She took Krista’s case to what’s known as “tumor board”: a gathering of medical professionals from multiple disciplines designed to discuss and make determinations about complex cancer cases.

“The radiologists are there, the pathologists are there, the radiation oncologists, GYN-oncologists — we’re all there to discuss everything in detail, put all the pieces together and come up with a plan,” Dr. Ciccone says.

Together, Dr. Ciccone and her colleagues developed an innovative approach.

“There’d been several instances in the case reports of combining a cervical-cancer treatment with a gastric-cancer protocol,” Dr. Ciccone says.

They decided not just to sensitize Krista’s tumor to radiation with cisplatin—a traditional cervical-cancer chemotherapy drug—but to also add to that regimen 5-fluorouracil, a chemotherapy agent often used to treat gastrointestinal cancers but also known for its use as a radiosensitizer with prior history of use in cervical cancer.

After radiation and chemotherapy came surgery — another somewhat unconventional move.

“For most cervical cancers, even when it’s more advanced or a larger tumor, radiation can cure you,” Dr. Ciccone says. “But knowing that this cancer might not respond fully to radiation, we planned to remove the uterus and cervix following chemotherapy and radiation to make sure we cleared out all of the tumor that was there.”

This proved to be an important step, as they did find more tumor during surgery.

Moreover, knowing that tumors like Krista’s sometimes migrate from the stomach or large bowel, her care team performed a colon resection along with the hysterectomy. “Not being sure if this was coming from the stomach or maybe the colon,” Dr. Ciccone says, “doing the colon surgery helped us answer that question.”

“Fortunately.” Dr. Ciccone reports, “the intestine wasn’t involved.”

Managing expectations for rare cancer treatment

According to Dr. Ciccone, managing expectations is always hard when treating — and battling — cancer. But it’s even harder when that cancer is so rare that you don’t even know what to expect.

Yet that’s the case with almost any cancer, she argues. “Cancers even within the same cell type behave differently,” she says. “You never know when you’re going to have that patient who responds really well.”

And Krista turned out to be just that. Four years on, regular scans and routine monitoring continue to confirm that Krista is in remission.

And she’s back at work, returning to the studio, mounting solo shows and creating art — albeit with a fresh perspective.

“My work has shifted,” she says. “And people have noticed it. They’ll say, ‘There’s something different here.’ And I’ll think, ‘Well, it’s because I’ve had a near-death experience! I didn’t quite see the light in the tunnel, but it happened.’”

Her experience has only redoubled her commitment to art, and her choice to make it her career.

“When you realize your life is finite, it reminds you that you’d better make it palatable,” she says. “So if anything, I’m more fiercely convinced that I am gonna do this. This is what I’ve chosen to do.”

Among the art she’s made since returning to the studio is a mixed-media work titled “Playing the Hand You’re Dealt.” As Krista says, “Cancer was the hand I was dealt, and it didn’t make sense.”

But that hand also hid some aces. “I landed an ace of a doctor,” she says, “and this teaching hospital — which I love.”

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