Rising Incidence of Head and Neck Cancer Drives Treatment Advances

After years of decline driven by successful tobacco cessation efforts, certain head and neck cancers—particularly oropharyngeal cancers—are on the rise in the US, largely due to increasing rates of infection with high-risk strains of human papillomavirus (HPV).

“The traditional cancers associated with tobacco consumption, such as mouth, tongue, and larynx cancer, have decreased,” said Dennis H. Kraus, MD, FACS, ACS Second Vice-President. “But other cancers, especially those related to HPV, are increasing significantly.”

Head and neck cancers are a diverse, challenging disease group because they are near vital organs and complex in nature, and their treatments have the potential for significant side effects. The tumors’ proximity to structures like the larynx, salivary glands, and nerves can make it difficult to effectively target cancer cells without damaging healthy tissue.

Despite its morbidity, open surgery was once the mainstay of treatment for head and neck cancer, Dr. Kraus said. Then radiation and chemotherapy showed effectiveness but came with toxic side effects.

In recent years, minimally invasive surgical techniques and robotic-assisted surgery have been shown to treat head and neck cancers with less morbidity. Meanwhile, efforts to make radiation and chemotherapy more effective and less toxic are advancing, as are promising new developments in immunotherapy.

Since these treatments often are used in combination, effectively treating, reconstructing, and rehabilitating the head and neck cancer patient requires a multidisciplinary team.

Evolving Nature, Risk Factors

Head and neck cancers usually begin in the squamous cells that line the mucosal surfaces of the head and neck, or, less commonly, in the salivary glands, sinuses, or muscles and nerves in the head and neck.¹ Other head and neck cancers include skin cancer and thyroid cancer.²

“Head and neck cancer is not one single cancer, it’s a constituency of diseases,” Dr. Kraus said.

The National Cancer Institute estimates that approximately 72,680 people in the US will be diagnosed with a major type of head and neck cancer—oral cavity, pharynx, or larynx cancer—in 2025. An estimated 16,680 people will die from these diseases.³

Most head and neck cancers can be divided into two different categories—those related to HPV and those that are not, said Jamie A. Ku, MD, FACS, director of the Head and Neck Robotic Surgery Program at the Cleveland Clinic in Ohio.

Historically, most head and neck cancers in the US were caused by tobacco use, often combined with alcohol use, and typically affected men 50 years and older.

Currently, though, HPV-driven cancers represent a large proportion of new head and neck cancer diagnoses in the US, which occur more commonly in men who are in their 40s or older, but also in women, said Ryan J. Li, MD, MBA, FACS, professor and chief of the Division of Head and Neck Surgery at Oregon Health & Science University in Portland.

“These patients are younger, healthier, and usually nonsmokers. They also have a slightly higher socioeconomic and educational background,” Dr. Ku said.

Tobacco-related head and neck cancers, however, are still prevalent in much of the world and are the third-most prevalent cancer, according to the Global Cancer Statistics of 2020. These diseases account for 7.6% of all cancers, 4.8% of all cancer-related deaths, and are predicted to rise 30% annually until 2030.^4,5

“In Southeast Asia and India, oral cancer related to tobacco use and betel nut chewing is a major epidemic,” Dr. Li said.

Other risk factors include alcohol, environmental and occupational exposures (such as wood dust and mining), and genetic predisposition.

HPV Leads to Cancer Resurgence

HPV is the most common sexually transmitted infection in the world. Although most people resolve HPV infection without medical intervention, HPV-driven head and neck cancer can remain latent, grow slowly, and may not appear for years.⁶ In the US, head and neck cancers now surpass cervical cancer as the most common HPV-related malignancy, in part due to the success of cervical cancer screening.⁷

The rise in HPV-driven head and neck cancers in the US may be in part due to substantial differences in sexual practices in North America, Dr. Li said. The number of oral sex partners is a risk factor associated with HPV-related head and neck cancer, specifically oropharyngeal cancer.

HPV cancers have risen despite the introduction of the HPV vaccine in 2006 for girls and young women, and a few years later, for boys and young men. The most recent vaccine protects against nine high-risk HPV variants and is typically offered to patients upon their sexual debut up to the age of 26, but clinicians and patients can consider vaccination up to age 45 years, Dr. Li explained.

According to Dr. Ku, it may take 20 to 30 years before the HPV vaccine starts to reduce HPV-driven head and neck cancers.

Multidisciplinary Team Approach

Multidisciplinary collaboration is important when developing a patient plan that considers the roles of surgery, radiation, and systemic therapy, Dr. Li said.

The team typically includes surgeons, particularly otolaryngologists and head and neck, maxillofacial, and reconstructive specialists. At some US centers and around the world, this team includes general surgeons who subspecialize in head and neck cancer surgery, Dr. Li explained. In addition, many other specialists engage in treatment, reconstruction, and rehabilitation of these patients, including pathologists, radiologists, radiation and medical oncologists, speech and language pathologists, dentists, and nutritionists.

“Multidisciplinary care, especially for these complex head and neck cancer patients, is very important,” Dr. Ku said. “Patients should not be seeing just a surgeon. They should be under the care of a well-run team of specialists.”

“High-Risk Real Estate”

Cancer in the head and neck area can affect a patient’s appearance and sense of identity, as well as their ability to speak, swallow, and interact with others.

“The head and neck are very high-risk real estate,” Dr. Ku shared.

Minimally invasive and reconstructive techniques are critical to protecting patient quality of life. As a result, treatment decisions must take into account not just effectiveness in treating the cancer but also potential side effects—both short and long term. Radiation toxicity, for example, can potentially create quality-of-life issues, especially around swallowing and speech functions and dental and oral cavity health.

“That’s why patient selection is such a critical art and why surgeons must help patients understand the advantages and disadvantages of each approach,” Dr. Li said.

The effects of toxic radiation have become a rising concern in the US as HPV-driven cancers have become the most common cause of head and neck cancer.

HPV-related head and neck cancers, which primarily occur in the oropharynx behind the oral cavity, have a higher probability of cure than the classic head and neck cancer diagnosis that was related to tobacco use, Dr. Li said, adding that the longer the patient lives after treatment, the more likely the cumulative effects and toxicity of radiation can affect them post-treatment.

“They have a longer runway of time to experience adverse effects,” he said.

Restoring Appearance, Function, and Quality of Life

Reconstruction has made many advances over the last few decades, particularly complex reconstruction.

Up to 3 decades ago, a large resection of the jaw would leave the patient without the profile of their jaw, Dr. Kraus said. Now, titanium implants and prosthetic teeth implants can be used in reconstruction, as can tissue transferred from other parts of the body, such as the leg, hip, scapula, or forearm.

Patients who have a large cancer removed from their oral cavity, such as their tongue, often need immediate reconstruction as the resulting surgical wound is not compatible with life or function, Dr. Li explained.

As a result, many reconstructive surgeries are performed at the time of cancer removal, often with one team of surgeons removing the cancer in tandem with another team preparing to reconstruct the surgical site.

“Collaboration between ablative and reconstructive teams reduces the length of time a patient is under general anesthesia,” he said.

Reconstruction cases can take from 6 to 12 hours, or longer if there are technical challenges, and even the best efforts may not be able to fully restore functions such as speech and swallowing. As a result, patients must be counseled as to what functional deficits to anticipate. Speech-language pathologist support is central to preparing patients for life-changing consequences of treatments.

Advances in Diagnosis and Early Detection

Like most cancers, head and neck cancers are more treatable and curable if found early.

The most effective screening efforts for head and neck cancers often are the result of routine primary care and dental oral care examinations, Dr. Ku said.

Tests can profile a patient’s tumor and identify the molecular basis for malignancy, according to Dr. Kraus. For example, some tests use molecular markers to risk-stratify the malignancy in thyroid neoplasms. Previously, patients with an indeterminate thyroid nodule would require an open surgical procedure.

Finally, there are efforts to identify head and neck cancer biomarkers from tissue or liquid specimen, such as blood, Dr. Ku said. Blood tests or “liquid biopsies,” will be a major component of future diagnostics for patients as well as monitoring their response to treatment.

Molecular and genetic markers can be used during surveillance to predict tumor behavior and can determine if there is minimal residual disease by looking for tumor DNA circulating in the blood. This approach can inform surgical decision-making; eventually, these markers also could be used for diagnostic purposes, she shared.

And in the future, AI could help evaluate blood tests and biopsies.

Advances in Biopsies

There have been many advances in biopsy technology for head and neck cancer.

A key advancement in this area is the sentinel lymph node biopsy, which is used in early stage squamous cell carcinoma to reduce unnecessary neck dissections. This preserves the patient’s immune system to help them fight cancer.

“Rather than perform a huge operation to remove all of the lymph nodes on one side of the head and neck, we now take out one or two lymph nodes, which are then evaluated for cancer,” Dr. Kraus said.

According to Dr. Li, for patients with a neck mass without a clear primary site, physicians now test a confirmed cancer for expression of a protein that is commonly a surrogate marker for HPV—a protein called p16—that can indicate a hard-to-see cancer that originated in the oropharynx.

A thorough endoscopy of the upper aerodigestive tract can identify and biopsy suspicious lesions, and for hard-to-reach or -see areas of the throat, biopsies can be done using robotic systems or interventional radiology expertise, he explained.

Advances in Minimally Invasive and Robotic-Assisted Surgical Techniques

In the past, radical open surgeries were performed on hard-to-reach areas, resulting in a temporary tracheostomy and a feeding tube. Now, there are multiple tools to access these areas.

For example, transoral robotic surgery uses small instrumentations and articulating arms to reach tight, remote areas performed by endoscopic visualization tools, Dr. Ku said, explaining that a surgical micro robotic system with microsurgical tools also is being explored.

Patients who receive robotic resection of the primary tumor in the back of the oropharynx may avoid morbid neck dissection, have a lower risk for recurrence, and may no longer need chemotherapy or radiation (or require lower doses), Dr. Kraus said.

As in other industries, artificial intelligence (AI) is likely to have an increasing role in imaging and pathologic analysis and could soon be used in preoperative planning and risk stratification in head and neck cancer surgery. It could even help plan the surgery, Dr. Li said, adding that a major factor in the success of such computing advances is the quality of data that are input into analytical platforms.

This AI-guided approach is common in sinus surgery for some noncancer and cancer cases, but so far, it hasn’t been applied much to head and neck cancer surgery.

Immunotherapy and Other Developments

For years, attempts to improve overall survival or quality of life in the adjuvant phase for head and neck cancer patients were unsuccessful. Recently, however, immunotherapy has shown success in treating these patients, such as those with advanced squamous skin cancer.

“In terms of both oncologic outcome and functional, quality of life, and cosmetic outcomes, immunotherapy will lead to significant improvement in the way we treat these patients,” Dr. Ku said.

In addition, checkpoint inhibitors, such as pembrolizumab, also have shown progress in treating recurrent or metastatic disease, and more recently in the primary treatment of head and neck cancers, Dr. Li shared. The Keynote-689 study showed that checkpoint inhibitors, in combination with standard of care treatment, produce significant benefits in treating various locally advanced head and neck cancers, including cancers of the larynx, hypopharynx, oropharynx, and oral cavity.

“This is one of the most exciting paradigm changes that likely will be widely adopted in the treatment of head and neck cancer, as it stands to materially improve pathological response and survival rates in many patients in an area where movement of survival rates have largely remained stagnant,” noted Dr. Li.

Other new treatment developments include:

• Targeted radiation: Radiomics is an area in which radiation will target cells with molecular changes. In addition, studies are underway to reduce the dose and/or volume of radiation based on when or in what combination with other treatments it is delivered.
• Advances in personalized medicine: Tumor genetic profiling can guide surgical decisions and target therapies. “Based on your own molecular markers, we’re now able to use much more specific drugs and really target those molecular events,” Dr. Kraus said.
• Novel therapies: Therapies such as vaccines beyond the HPV vaccine; for example, a melanoma vaccine is in development.
• Bioengineered tissues and regenerative medicine in reconstruction: These approaches aim to create biocompatible, tailor-made tissues that can be implanted to restore functionality and appearance.

As the treatment of head and neck cancer continues to evolve, with increasingly sophisticated diagnostic tools and expanding treatment options, the role of the multidisciplinary care team—led by the surgeon—has never been more important. Advances in minimally invasive surgery, reconstructive techniques, immunotherapy, and personalized medicine are transforming outcomes, offering patients improved survival and better function and quality of life. Yet with the rise of HPV-driven disease, the challenges remain complex. Continued collaboration, innovation, and patient-centered care will be essential to shaping the future of this cancer treatment.

Jim McCartney is a freelance writer.

References

1. National Cancer Institute. Head and neck cancers fact sheet. May 25, 2021. Available at: https://www.cancer.gov/types/head-and-neck/head-neck-fact-sheet. Accessed June 23, 2025.
2. Centers for Disease Control and Prevention. Head and neck cancers basics. Available at: https://www.cdc.gov/head-neck-cancer/about/index.html#:~:text=Cancers%20of%20the%20head%20and,Inside%20and%20behind%20the%20nose. Accessed June 23, 2025.
3. American Association for Cancer Research. Head and neck cancers. Available at: https://www.aacr.org/patients-caregivers/cancer/head-and-neck-cancers/#:~:text=The%20National%20Cancer%20Institute%20estimates%20that%20about,16%2C680%20people%20will%20die%20from%20these%20diseases. Accessed June 23, 2025.
4. Sung H, Ferlay J, Siegel RL, Laversanne M, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. May 2021;71(3):209-249.
5. Gormley M, Creaney G, Schache A, et al. Reviewing the epidemiology of head and neck cancer: Definitions, trends and risk factors. Br Dent J. 2022; 233(9):780-786.
6. Persky MS, Hu KS. Five things to know about HPV and throat cancer. NYU Langone Health Perlmutter Cancer Center Magazine. Fall 2021. Available at: https://nyulangone.org/news/five-things-know-about-hpv-throat-cancer#:~:text=HPV%20Is%20Common%2C%20But%20Some%20Types%20Cause%20Cancer&text=In%20most%20cases%2C%20the%20immune,the%20tonsils%2C%E2%80%9D%20explains%20Dr. Accessed June 23, 2025.
7. Roman BR, Aragones A. Epidemiology and incidence of HPV-related cancers of the head and neck. J Surg Oncol. 2021;124(6):920-922.