Cervical Cancer Awareness Month: Vaccines and Early Detection Remain Critical

Robert P. Edwards, MD

From pap smears to human papillomavirus (HPV) testing to the promise of therapeutic vaccines and immunotherapy, the landscape of cervical cancer treatment has offered optimism for patients. Still, better outcomes for patients with cervical cancer heavily rely on early detection.

Robert P. Edwards, MD, shed light on the role of screening methods like HPV testing and vaccination, and underscored the importance of breaking down stigmas in the cervical cancer space. According to Edwards, increased public awareness, including advocating for stronger survivor voices and research investment, can help pave the way for a future that is free from this preventable disease.

In an interview with Targeted Oncology^TM for Cervical Cancer Awareness Month, Edwards, a professor of medicine and Department of OBGYN at the University of Pittsburgh School of Medicine (UPMC), and a senior vice president for UPMC enterprises and community and ambulatory, discussed the current treatment landscape of cervical cancer as well as future prospects.

Targeted Oncology: What are the current or most recent advancements in cervical cancer treatment that patients should be aware of?

Edwards: In cervical cancer, the gold standard for cancer screening was the pap smear. The pap smear was created by a Greek clinician named Papanicolaou in the 1930s. It took about 30 years before it became accepted and was recognized to be a standard of cancer screening. From the early 60s all the way until 2010, I would say the pap smear has been the gold standard for all cancer screening approaches. Now, the pap smear is a screening test for abnormal-appearing cells. It's basically just a survey of a very small region of the cervix. The cervix has a higher cancer risk because of 2 factors: human papillomavirus and the fact that the cervix changes its epithelial appearance as women age. That changing process, together with carcinogenic human papillomavirus, leads to cancer risk. I went through that explanation to say that the pap smear detected the cells, but the better testing has revolved around HPV detection.

It took about 20 years, the length of my career, to figure out how to use human papillomavirus testing to get a sense of test properties, but not it is clear that age is a cofactor in the ability of molecular testing to determine cancer risk. That is, the older the patient is beyond age 20, the better the performance of HPV testing. We're now at the point where for most women, HPV testing is probably the better test than the pap smear. This would be the first advance, the use of DNA molecular testing instead of cervical cytology as a standard-of-care for detection of precancerous lesions.

The second innovation and the thing I've been most heavily involved in because my background is in cancer immunology and prevention was the development of the HPV vaccine. My postdoctoral training was in the immune response to human papillomavirus, particularly in the cervix, but also in systemic immune responses in other organs in the body the oral cavity and other carcinogenic sites. In conjunction with Merck and GSK, 2 vaccine products were developed that are now approved by the FDA. From a perspective of patients and population health, human papillomavirus preventive vaccine is probably the greatest advance we've seen in cancer to this point. It is still not available in many [developing] countries because of the cost, but theoretically, if the entire population of women in the world had access and were compliant with the use of human papillomavirus vaccine, we'd reduce cervical cancer by at least tenfold. Like most vaccines, there have been some disinformation and anti-vaccine sentiments, but none of it is substantiated by any evidence of based on long-term outcomes from these studies from the late 90s. There are 2 barriers to accepting human papillomavirus vaccine: the public attitude towards vaccines in general [and] the cost.

Can you explain the importance of early detection and screening methods for cervical cancer?

Cervical cancer is one of the few cancers where we have a clearly defined progression from infection to pre-cancer, to cancer, again, associated with human papillomavirus. Cervical cancer is the number 2 leading cause of death for cancer in the world. Lung cancer surpassed it about 15 years ago because of smoking. More women have breast cancer, but more women don't die from breast cancer worldwide. It is cervical cancer. There's still a lot of opportunity here to prevent it. The best way to prevent cervical cancer, other than if you're past the age where you're appropriate for effective vaccination, is to get the screening methods we talked about. The earlier they're started, the more likely they are to prevent cancer, but also, the more likely they are to detect a transient abnormality. That's why we wait now beyond age 20, or after sexual debut, the term commonly used for it, to begin screening women, because they are not really at risk of developing cervical cancer until they become sexually active. Women who are vaccinated now make up about 40% of the population in the United States for ages 20-30. The biology and the population biology of this is changing. In 20-30 years from now, we may not even be doing pap smears or HPV testing. If we have a high penetration of the vaccination practices, at least in the United States, the prevalence of this cancer will be extremely low in the United States and other developed countries.

Are there any notable breakthroughs or promising research in cervical cancer that you find particularly exciting?

There are 2. Unfortunately, most women, particularly if they're over age 20, the vaccine was approved in 2005, became publicly available in 2006, and the uptake in compliance was really under 20% until about 2010 when the CDC got behind the human papillomavirus vaccination. The peak age to get vaccinated is before age 15. That's almost exclusively predicated on when the average woman in the United States will begin to think about becoming sexually active. Once a woman becomes sexually active, you can still give the preventive vaccine, but it's not as effective as if you give it before women become sexually active. Most obstetrician gynecologists and pediatricians are now recommending it be done about the time of first period, ages 11, 12, or 13.

For women who are already colonized and have the virus, there are 2 products that are exciting. One is what are called therapeutic vaccines. Therapeutic vaccines are now being actively tested in a number of human papillomavirus entities, including head, neck, and cervix cancer. The preliminary efficacy was not as high as for a prophylactic or preventative vaccine. But it is pretty good, so I expect therapeutic vaccines to continue to improve their performance and be available to the public in the next 5 years. The second innovation that's already available is the use of checkpoint inhibitors like [pembrolizumab] and others. Those are now active for cervical cancer. Because cervical cancers have virally induced cancer, it is particularly responsive to immune therapies like checkpoint inhibitors. Those are the 2 things coming down the pike that I think hold additional hope for women who already have cervical cancer or have cervix pre-cancer and can't get it to resolve.

What improvements do you foresee?

There are 2 branches of immunotherapy. One is vaccines and the other is immune modulation or immune activation. Vaccines are then divided into preventive and therapeutic. The next step is likely to combine therapeutic vaccines with immunomodulation like checkpoint inhibitors. The third element of that that we’re beginning to see now is use of either radiation or chemotherapy in conjunction with both vaccines and any modulation, like checkpoint inhibitors. [We are] going to see combination immunotherapies in the future since a single immunotherapy therapeutic regimen has an efficacy of about 20%-30%. It’s not anywhere near 100% like how preventive vaccination is.

Can you provide insights into the role of immunotherapy in cervical cancer treatment and its potential impact on patient outcomes?

It comes down to availability and attitudes of the public toward cervical cancer. Cervical cancer is a disease of women. I think it’s associated with sexual activity, not promiscuity, but just activity. Somehow it has a negative stigma about it, and it really shouldn't. It's not a disease of poor choices or being poor. It's a disease that afflicts everybody. The only difference between [those who live in] poor [compared with] more developed countries is access to healthcare and prevention.

Are there specific challenges related to cervical cancer that you think need more public awareness?

I think there's a lack of ownership of cervix cancer by the survivors. Cervical cancer awareness month is a great initiative, but it's never taken off like breast cancer or ovarian cancer, probably because of the stigma associated with it. It would be helpful if there was a survivorship leadership initiative of folks who could influence policy and decision making. Cervical cancer is an underfunded cancer compared with breast, ovarian, or lymphomas. People at the National Cancer Institute think, well, we've got a vaccine to prevent it, so we don't need to invest in this disease anymore. It's a prevalent disease, both in this country particularly in areas of Appalachia, and in the [developing] world. As I stated, it remains the second most common cancer in women. Unfortunately, those who get cervix cancer tend to be the people who have the least amount of power in society. The influence is limited unless people who are involved in policy realize the public health epidemic that cervix cancer presents.

What should a community oncologist know moving forward with research in this space?

A community oncologist should understand the importance of treatment planning and cervical cancer specialists in the management of this disease. Like most solid tumors, if you don't apply the proper treatment out of the gate and have a clear treatment plan, you've lost the battle. For both community oncologists and women themselves [who are] afflicted, it is important to [see a] specialist to get that initial treatment and plan. Most treatment plans can be instituted in the community hospital setting, but they should be designed because of a rare disease with about 7000 cases a year in the United States, and more in [developing] countries. If they don't do the proper treatment, whether it's radiation, surgery, or even chemotherapy out of the gate, recurrent patients tend to die of their disease in very high numbers. My advice is because it is a rare disease compared with, say, lymphoma, it's worth the drive to go get opinion from a specialist on how to manage it.

With it being cervical cancer awareness month, what do you believe is most important to highlight?

It's a disease that I'm proud to say I think my career, particularly in the early stages of my career, has been devoted to. We've seen, not due to my contributions, but to the overall field making progress, the dynamics of this change significantly. I think we have enough tools to make an impact and make this a historic cancer, but it's going to take public awareness and an appreciation and acceptance of preventative strategies like vaccines to get there.