Oropharyngeal squamous cell carcinoma is a cancer arising from the oropharynx (back of the mouth) which includes the tonsils, base of tongue, soft palate, and posterior pharyngeal wall. Over 90% of oropharyngeal cancers are squamous cell carcinomas. HPV has been found to cause cancer of the genital organs in both men and women, oropharynx, as well as benign conditions like genital and cutaneous warts.

Epidemiology and Risk Factors  

The recent analyses of cancer registry data show dramatic increases in the incidence of oropharyngeal carcinomas during the past 15–20 years as the incidence of oral cavity carcinomas has remained constant or declined. 

HPV+ OPSCC typically affects younger patients, often nonsmokers. HPV-negative disease still occurs, mainly in older adults with heavy smoking and alcohol history.

Oral HPV infection was independently linked to factors such as age, sex, number of sexual partners and the current number of cigarettes smoked per day.(19) In recent times it was also found to be linked to alcohol, genetic polymorphisms. Smoking is known to decrease the clearance of oral HPV infections.

The incidence of human papillomavirus-associated oropharyngeal cancer (HPV+OPSCC) is continuing to rise over the coming decades until the benefits of gender-neutral prophylactic HPV vaccination begin to become manifest.  

 Clinical Presentation  

High-risk HPV infections are asymptomatic, and most persons exposed to HPV will clear the infection and never develop carcinoma.

Common symptoms include a painless neck mass, sore throat, dysphagia, otalgia, trismus, and voice changes. Primary tumors can be subtle, especially at the base of tongue.  Importantly, OPSCC is often detected at an advanced stage owing to a lack of symptoms in the early stages; therefore, a need exists to identify and validate possible diagnostic biomarkers to aid in earlier detection.

Diagnosis and Staging  

Diagnosis requires biopsy of the primary or node, with p16 testing to determine HPV status. Workup includes CT/MRI neck, PET-CT, and EUA with biopsies. 

Prevention, Prognosis and Management  

With the advent of vaccines that can prevent HPV infection, the World Health Organization has made eliminating HPV and its related cancers a global health priority. Treatment decisions depend on exact staging , patient fitness , smoking history  and surgical resectability.

Early stages can be treated with surgery or RT with post op adjuvant RT or CT RT.

Locally advanced stages are treated with concurrent CTRT or induction chemo.

Recurrence and metastasis are treated with immunotherapies.

HPV+ OPSCC has markedly better outcomes, with 3-year survival ∼85-90% for early stage vs ∼60% for HPV-negative.  Because HPV+ patients are younger and live longer, treatment de-escalation trials are ongoing to reduce long-term toxicity.

Dr Saumya Verma 

MBBS, DNB 

Immunotherapy is a form of cancer treatment that enhances the body's natural immune defenses to recognize and destroy cancer cells. The immune system, which consists of white blood cells along with the organs and tissues of the lymphatic system, plays a vital role in the body against infections and diseases. It keeps track of what normally belongs in the body. When it finds something that it either doesn’t recognize, or recognizes as “foreign,” the immune system raises an alarm and attacks it. This is called the immune response. Under normal conditions, it identifies and eliminates abnormal cells, thereby helping to prevent the development and progression of many cancers.

Immunotherapy is a form of biological therapy that utilizes naturally occurring or laboratory-produced substances to enhance the body's immune response against cancer. These laboratory-made agents mimic components of the immune system, helping it recognize and attack cancer cells more effectively. Although the immune system can detect and control the growth of cancer, cancer cells can develop mechanisms to evade immune surveillance and destruction. Immunotherapy works by strengthening or restoring the immune system’s ability to identify and eliminate cancer cells more effectively.

Types of Immunotherapy

Immune checkpoint inhibitors are drugs that block immune checkpoints, which normally regulate the immune system and prevent overactive immune responses.

T-cell transfer therapy (also called adoptive cell therapy or immune cell therapy) is a type of immunotherapy that enhances the ability of a patient's T cells to recognize and destroy cancer cells.

Monoclonal antibodies (therapeutic antibodies) are laboratory-produced immune proteins designed to target specific molecules on cancer cells. Some of these antibodies help the immune system by marking and attack cancer cells more effectively.

Treatment vaccines, which work against cancer by boosting your immune system’s response to cancer cells.

Immune system modulators, which enhance the body’s immune response against cancer.

Some others are Chimeric Antigen Receptor (CAR) T cell therapy and Cytokines

Commonly Used Immunotherapy Drugs

Several immune checkpoint inhibitors are currently used in routine oncology practice. These include:

• Pembrolizumab

• Nivolumab

• Atezolizumab

• Durvalumab

• Ipilimumab

• Cemiplimab

Many of these agents are available in India and are increasingly being incorporated into treatment protocols for a variety of cancers.

How Is Immunotherapy Different from Chemotherapy?

 Chemotherapy acts by directly damaging rapidly dividing cells. While effective against many cancers, it can also affect normal tissues such as the bone marrow, gastrointestinal tract, and hair follicles, resulting in familiar side effects such as low blood counts, nausea, and hair loss.

Immunotherapy works through a different mechanism. Rather than directly attacking the tumor, it stimulates immune cells to recognize and respond to cancer.

Uses of immunotherapy in Cancer

Immunotherapy has been approved for the treatment of various cancers, It is most often employed in advanced-stage cancers and  particularly when conventional treatments are not working. Also there is upcoming established role in locally advanced stages also in few cancers. It is now anestablished treatment option for several malignancies, including:

• Lung cancer

• Head and neck squamous cell carcinoma

• Melanoma

• Kidney cancer

• Bladder cancer

• Cervical cancer

• Endometrial cancer

• Esophageal cancer

• Gastric cancer

• Hodgkin lymphoma

• Certain colorectal cancers

In India, immunotherapy has assumed particular importance in the management of lung cancer and head and neck cancers, which together account for a substantial proportion of the country's cancer burden.

Research continues to identify new indications and treatment combinations, further expanding the role of immunotherapy in cancer care.

Contraindications of Immunotherapy

·        Active Autoimmune Disease like Active Lupus, Rheumatoid Arthritis, Chron’s disease, Ulcerative Colitis, Myasthenia Gravis, Vasculitis

·        Solid Organ Transplant

·        Need for high dose steroids for systemic immunosuppression

·        Pregnancy and Breastfeeding

·        History of severe immune related toxicity to prior immunotherapy treatment

Goal of immunotherapy

If immunotherapy is recommended, it is important to understand the purpose of the treatment. The treatment goal depends on the type and stage of cancer, as well as the extent of its spread. Immunotherapy may be used with one of three objectives:

1. Cure the cancer (curative intent)

2. Control its growth and progression

3. Relieve symptoms and improve quality of life (palliative intent)

One of the most encouraging observations from clinical studies is that a subset of patients experiences prolonged disease control, even in the setting of advanced cancer. While such outcomes cannot be guaranteed, they have contributed substantially to the growing enthusiasm surrounding immunotherapy.

Side effects of immunotherapy

About 70 to 80 % of patients experience no side effects, while 20 to 30 % of patients experience minimal to mild side effects like skin reactions, flu like symptoms or changes in thyroid function.

Most common skin reactions seen are pain, swelling, soreness, redness, itchiness or rash. Flu-like symptoms mainly fever, chills, weakness, dizziness, muscle and joint pain, fatigue and headache. Most symptoms improve over time with supportive medications.

Some types of immunotherapies may rarely cause severe or fatal allergic and inflammation-related reactions like hepatitis, pneumonitis, colitis, adrenal insufficiency, nephritis are seen in 1 to 2 % population.

Most immune-related side effects can be managed successfully when identified early. For this reason, patients receiving immunotherapy should promptly report new symptoms to their healthcare team. Early recognition and treatment remain critical to ensuring patient safety.

How often do you receive immunotherapy?

This depends on the type of cancer, its stage and grade, the type of immunotherapy and mainly how your body reacts to treatment.  Immunotherapy infusions are typically scheduled every 2, 3, 4 or 6 weeks, depending on the treatment regimen.

How can you tell if immunotherapy is working?

 You will have medical tests, such as blood tests and different types of scans. These tests will measure the size of your tumor, and the doctor will look for changes in your blood work.

Is there a possibility that the treatment plans will change after starting immunotherapy once? 

Yes indeed. There may be times when there are serious side effects which will require changes in the dose or timing of the medications or including supportive medications which will give your body more time to recover.  It’s important, whenever possible, to get the full course of immunotherapy, the full dose, and keep the cycles on schedule. This gives you the best chance of getting the maximum benefit from treatment.

Sometimes, cancer cells develop resistance to a certain immunotherapy and a different treatment might be tried.

Conclusion

Immunotherapy represents a major milestone in oncology. By harnessing the body's own immune system to combat cancer, it has created new treatment opportunities for patients with a wide range of malignancies. Although it is not suitable for every patient and does not replace traditional treatment modalities, immunotherapy has significantly improved outcomes for many individuals and continues to reshape the future of cancer treatment.

As research progresses, the promise of more effective, personalized, and durable cancer therapies is becoming increasingly achievable.

Dr. Saumya Verma

MBBS, DNB 

References

https://www.cancer.gov/about-cancer/treatment/types/immunotherapy

https://www.cancer.org/cancer/managing-cancer/treatment-types/immunotherapy.html