Herpes: An Unexpected Cancer Therapy

With an estimated 3.7 billion people under 50 worldwide infected with the virus that causes cold sores,¹ we’re all pretty familiar with herpes. A further 491 million have the variant that causes genital herpes.¹ While herpes is usually manageable, it can be dangerous in some cases.

Another immense health concern is cancer, which causes one in six deaths globally. Because one in five people will develop cancer before the age of 75 and rates are rapidly increasing,² researchers are heavily focused on finding a cure. In 2020, the National Cancer Institute (NCI) had over $6 billion at its disposal for research.³

So, how are herpes and cancer related? Revolutionary new herpes-based cancer treatments have shown a lot of promise. While one type of herpes simplex virus, HSV-2, can contribute to cancer,⁴ the HSV-1 type can treat it.

This might sound too good to be true, but the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have already approved a herpes-based treatment for cancer. Ready to find out more?

What is herpes?

Herpes is a common infection with the herpes simplex virus (HSV). There are two types of the virus: HSV-1 and HSV-2.

HSV-1 spreads through oral-to-oral contact and causes cold sores. Less commonly, it can also lead to genital herpes.

HSV-2 is a sexually transmitted infection (STI) that causes genital herpes.

The World Health Organization (WHO) states that HSV-1 affects 67% of people under 50, while HSV-2 affects 13% of people under 50.¹

When you first contract the virus, your symptoms will appear within 2–20 days. You might experience the following symptoms during your first outbreak:

• Pain and itching

• Fever

• Fatigue

• Swollen lymph nodes

• Headache and other body aches

• Generally feeling unwell

According to the Centers for Disease Control (CDC), many people have HSV-2 without noticeable symptoms.⁵ Others mistake minor symptoms for another skin condition.

Symptoms of HSV-1

• Blisters (cold sores) around the mouth and lips

• Blisters in other places: the face, tongue, and (rarely) on other parts of your body

Typically, your first outbreak of sores lasts 2–3 weeks before clearing up. 33% of people with HSV-1 experience recurring symptoms, with later outbreaks usually lasting 8–10 days.⁶

Symptoms of HSV-2

• Sores on your genitals, buttocks, or anus (they can also be on other areas)

• Change in vaginal discharge

• Pain while urinating

• Tingling, burning, or itching around the genitals

Sores last 2–6 weeks the first time they develop. They may recur shortly afterward, but outbreaks may be less frequent and severe the longer you have the virus.⁷ Later outbreaks typically last 8–10 days,⁶ like oral herpes.

Research has found that genital herpes symptoms recur in 50% of people who get it.⁶ Conversely, some people may never have an outbreak or know they have the virus.

Treatment for herpes

There is no cure for herpes, but antiviral medications may prevent or shorten outbreaks while you take the drug.

Another option is daily suppressive therapy, where you take an antiviral every day to reduce the likelihood of transmission to your partner.

Antivirals include acyclovir (Sitavig or Zovirax), famciclovir (Famvir), and valacyclovir (Valtrex). Like all medications, antivirals can cause side effects, so ask your doctor if they’re appropriate for you.

Herpes can be deadly in pregnancy

Herpes typically causes outbreaks that clear up on their own and don’t cause any serious issues, but it can be dangerous in some cases.

Doctors don’t believe genital herpes causes miscarriages, but neonatal herpes could harm your baby. Tell your doctor if you’ve ever had a herpes infection or suspect you have it.

The neonatal herpes risk is higher (30–50%) if you have your first herpes outbreak during the third trimester (weeks 29–40).⁸ This is because your body may not have the time to produce IgG antibodies to protect your baby. Your doctor will prescribe an antiviral such as acyclovir to reduce your baby’s risk of infection.

If you have recurrent outbreaks, the risk of a neonatal herpes infection is much lower at 2–5%.⁸ This is because your body already has the antibodies to pass on to your baby. The risk is 0.02–0.05% if you’ve had previous outbreaks and are currently asymptomatic.

Your obstetrician will test your viral cultures to check your vaginal secretions for herpes. If the result is negative, they will usually suggest a natural birth. However, they may recommend a cesarean section to lower the risk to your baby if your HSV cultures are positive. They may also advise a cesarean section if you contract herpes for the first time in the last 4–6 weeks of your pregnancy.

Neonatal herpes takes on three forms:

• Skin, eyes, and mouth (SEM)

• Encephalitis

• Disseminated disease affecting multiple organs

Your baby’s symptoms may include:

• Irritability

• Blisters anywhere on their body

• Bleeding easily

• Jaundice (yellowing of the skin and eyes)

• Trouble breathing

  • Rapid breathing

  • Not breathing for short periods

  • Grunting

  • Blue appearance (cyanosis)

Speak to your postpartum care team urgently if your baby develops any of these symptoms.

The SEM variant is the least dangerous, but it can still progress and harm your baby without treatment.

Encephalitis is a dangerous swelling of the brain that requires urgent medical attention.

The disseminated variant affecting multiple organs is the most severe. If left untreated, it has a mortality rate of 80%.⁸

As neonatal herpes can occur after birth until your baby is six weeks old, it’s important to ensure that visitors and caregivers don’t unwittingly pass on the infection. You and others should avoid kissing your baby for the first few weeks and ensure that any herpes sores are covered.

If you suspect that any new sores could be from herpes, speak to your doctor and cover them until you’ve been tested.

Other herpes complications

HIV

If you have genital herpes (HSV-2), you are 2–3 times more likely to contract HIV with or without antiviral treatment.⁹ This is due to cell changes in the lesion areas, and other STIs cause similar HIV risk factors.

Worse symptoms if you’re immunocompromised

If you’re immunocompromised, you’re more likely to develop herpes more frequently with severe symptoms.¹

Rare complications from HSV-1 include encephalitis (brain swelling from infection) or keratitis (eye infection). Rarely, HSV-2 can cause disseminated infection and a type of brain infection called meningoencephalitis.

Bacterial infection

Occasionally, the blisters that appear during a herpes outbreak become infected with bacteria. In this case, you should speak to your doctor for treatment to ensure the infection doesn’t spread or worsen.

Symptoms include fever, redness around the blisters, and pus.

How to prevent herpes

Herpes spreads through oral and genital contact, so you’d expect herpes prevention to be as simple as avoiding contact with someone presenting with herpes symptoms. Unfortunately, herpes can spread even with safe sex practices and between people with no apparent symptoms.

Asymptomatic people can infect their sexual partners 10% of the time and shed the virus from areas a condom doesn’t cover.¹⁰

The CDC states: “The surest way to avoid transmission of STDs, including genital herpes, is to abstain from sexual contact, or to be in a long-term mutually monogamous relationship with a partner who has been tested for STDs and is known to be uninfected.”

However, many people opt for the freedom of non-traditional sexual relationships. Plus, a healthy sex life is good for us,¹¹ so complete abstinence is a big ask.

So, is there a realistic way to reduce skin-to-skin contact?

• Request your partner gets a full STI check, including a blood test to test for HSV.

• Practice safe sex — use condoms and dams correctly.

• Don’t have sex if you or a sexual partner have visible lesions. Get a test instead.

• If you or a partner has herpes, taking an antiviral can reduce the risk of transmission.

• Tell your sexual partner if you have herpes.

From causing cold sores to treating cancer

Herpes is a serious condition that can be dangerous in some cases. However, scientists have discovered an unlikely benefit of HSV-1: the cold sore virus has been used to create ground-breaking cancer treatments.

One treatment is T-VEC (Talimogene laherparepvec), also known as Imylgic. The FDA and EMA approved it for melanoma (skin cancer) treatment in 2015. So, how does it work?

T-VEC is an immunotherapy treatment that uses a genetically modified and weakened version of HSV-1 that doctors inject directly into melanoma. It’s an “oncolytic virus,” meaning scientists have specifically designed it to kill cancer. It can replicate inside the cancer cells and destroy them without damaging healthy cells.

Imlygic is the first melanoma treatment to use a virus.

Immunotherapy harnesses the power of our immune systems by teaching them to recognize and attack cancer cells. T-VEC overwhelms melanoma, kills cancer cells, and produces a protein called granulocyte-macrophage colony-stimulating factor (GM-CSF). This protein activates your immune system and helps it recognize and destroy cells, training your body to fight cancer.

Imlygic’s 24-month phase III OPTiM trial studied 436 patients with inoperable melanoma (stages IIIB to IV) that had spread to other body parts.¹² They compared the effects of injecting T-VEC with GM-CSF.

The researchers measured effectiveness by how well patients responded to treatment and if the response lasted at least six months. While the improvement in overall survival didn’t meet statistical significance, the OPTiM study discovered a subgroup where T-VEC performed well.

249 patients in the study had stage III melanoma, meaning it hadn’t spread to any other organs (metastasized). Of 163 patients treated with Imlygic, 25% (41 people) had a sustained response. Only 1 of 86 patients treated with GM-CSF had the same result.

67.2% of lesions directly injected with T-VEC responded, decreasing in size by at least 30%.¹³ 46% entirely resolved after a median of 18.4 weeks. Even 41% of non-visceral lesions that weren’t injected responded, with 30% completely resolving after 23 weeks.

Visceral lesions (lesions on the internal organs) did not respond so well. After 51.3 weeks, fewer than 10% responded completely. This suggests that T-VEC can control local disease well, but its systemic effects are weaker. As such, you may need additional treatment (e.g., chemotherapy) if your melanoma has metastasized.

Another benefit of immunotherapy is that it directly targets cancer cells. This means it typically causes fewer side effects than other treatments, like chemotherapy.

However, T-VEC can still cause side effects.¹⁴ Treatment over a period of at least six months will put your body under a lot of stress. You may experience inflammation during or after your treatment, which can cause serious side effects. 90% of patients receiving the therapy experience flu-like symptoms, which usually clear up after three days.

You cannot have a live vaccine during your treatment and for up to 12 months afterward. Speak to your doctor if you need any vaccinations. The COVID-19 vaccine is not a live vaccine, so your doctor may recommend you have it.

T-VEC is not suitable for everyone as it uses the herpes virus. If you’re pregnant, immunocompromised, or taking certain medications, your doctor may advise against it.

You must be very cautious, as the virus can spread to other parts of your body or people you’re in close contact with. This includes caregivers, household members, sex partners, or people sharing your bed.

You should avoid direct contact between your treatment sites, dressings, and bodily fluids with close contacts. During treatment, don’t have sex without a condom, avoid kissing if either of you has an open mouth sore, and dispose of all dressings safely. Be careful not to scratch or touch the injection sites on your body to avoid spreading the infection.

From end-of-life care to cancer-free

T-VEC isn’t the only cancer treatment to use a modified herpes simplex virus. RP2 is another, and it doesn’t just fight melanoma.

Much like T-VEC, RP2 replicates inside the cancer and produces GM-CSF. RP2 also creates GALV-GP-R, another molecule that spurs your immune system into action.

RP2 is in early-stage trials and recently completed phase I with impressive results.

Phase I trials are where researchers determine if novel treatments are safe, and they don’t typically produce results that demonstrate remarkable potential. One of the issues with early studies is that they don’t involve many participants, making it hard to assess treatment efficacy.

This RP2 trial had 39 participants who had exhausted all other treatments for their cancer, including immune checkpoint immunotherapy.¹⁵ At this stage, their cancers were considered untreatable.

The researchers tested RP2 in combination with nivolumab in 30 participants. Nivolumab is an immunotherapy drug that blocks PD-1, a protein that moderates your immune system to stop it from overreacting. Another nine participants had RP2 alone.

Three of the nine patients who received just RP2 saw their tumors shrink. One man’s tumor disappeared completely.

Here are other results from the trial:

• Salivary gland cancer (mucoepidermoid carcinoma): cancer-free two years on

• Esophageal cancer: cancer shrunk and did not progress for 18 months

• Eye cancer with liver metastases (uveal melanoma): cancer shrunk and did not progress for 15 months

Tumors changed in seven out of 30 patients who had RP2 and nivolumab treatment, including:

• Four patients with melanoma skin cancer

• Two patients with uveal melanoma (eye cancer)

• One patient with head and neck cancer

Their cancers shrunk or stopped growing. Six remained progression-free at 14 months.

While these are impressive results, we need to wait for more significant trial results to fully understand the potential of this treatment.

Still, let’s not understate that one man saw his tumor disappear completely after previously exhausting all options, including multiple surgeries. Going from end-of-life care to normalcy is a testament to the power of science and clinical trials.

Why doesn’t immunotherapy work for everyone?

As with all immunotherapies, T-VEC and RP2 aren’t effective in everyone. Cancer researchers are still trying to understand why some people don’t respond to treatment. Leading theories involve tumors mutating to develop resistance and T cells not working as they should.

T cells are a type of white blood cell that recognize infection, allergens, and cancer. Your body moderates your immune system to prevent these cells from attacking everything, including healthy tissue.

In 1995, researcher James Allison uncovered precisely how the body prevents T cells from indiscriminately attacking cells.¹⁶

Allison discovered an immune checkpoint called CTLA-4 — a protein on T cells that modulates your immune responses to ensure your body doesn’t harm healthy cells. When CTLA-4 is attached to another protein — B7 — it stops T cells from killing cancer cells.

Some immunotherapy drugs are immune checkpoint inhibitors (ICIs).¹⁷ These block CTLA-4 and other checkpoints like PD-1, releasing the brakes on your immune system and allowing your T cells to attack cancer cells.

The immune checkpoint inhibitors won’t work if your body isn’t producing enough T cells or they aren’t working properly. While immune checkpoints are an important defense against autoimmune conditions like arthritis, they can also be a barrier to immunotherapy treatment.¹⁸

Dendritic cells are another vital part of your immune system. They stimulate T cells. So, immunotherapy won’t be effective if you don’t have enough dendritic cells near the tumor.

Studies suggest other theories for why immunotherapy doesn’t work for some people, including age, hormones, diet, and intestinal flora.¹⁹ While aging typically comes with reduced immune function,²⁰ some larger studies have shown there isn’t much difference in response between older people and younger people receiving ICI immunotherapy.¹⁹

There seems to be a disparity between how males and females respond to immunotherapy, with the benefit being more pronounced in males. Researchers believe this relates to fat distribution and hormone differences.¹⁹

More research is needed to uncover why immunotherapy doesn’t work for everyone. Still, combining it with traditional treatments like chemotherapy can be promising.²¹

The lowdown

Cancer is responsible for ten million deaths a year worldwide.²² Finding treatments is vital, and researchers are doing everything possible to fight the disease.

While the cold sore virus might seem like an unlikely treatment, T-VEC is an approved immunotherapy that can reduce melanoma lesions. RP2 is promising as a novel treatment for other types of cancer, and time will tell how it performs in later clinical trials.

Sources:

1. Herpes simplex virus | World Health Organization

2. Are there more people diagnosed with cancer? | Office for National Statistics

3. 2021 NCI budget funding factbook - Research funding | NIH: National Cancer Institute

4. Cervical cancer: is herpes simplex virus type II a cofactor? (1995)

5. Genital herpes – CDC detailed fact sheet | Centers for Disease Control and Prevention (CDC)

6. Single-day treatment for orolabial and genital herpes: a brief review of pathogenesis and pharmacology (2008)

7. Disease control priorities in developing countries. 2nd edition. Chapter 17 sexually transmitted infections (2006)

8. Herpes simplex virus infection in pregnancy (2012)

9. Why genital herpes boosts the risk of HIV infection | NIH: National Institute of Health

10. Genital shedding of herpes simplex virus among symptomatic and asymptomatic persons with HSV-2 infection (2011)

11. The benefits of a healthy sex life | Oregon Health & Science University

12. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma (2015)

13. Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study (2016)

14. Talimogene laherparepvec (T-VEC) | Cancer Research UK

15. 827P - An open-label, multicenter, phase I study of RP2 as a single agent and in combination with nivolumab in patients with solid tumors: Safety, efficacy, and biomarker results (2022)

16. Immunotherapy scientist stories: James P. Allison, PhD | CRI: Cancer Research Institute

17. Immune checkpoint inhibitors | NIH: National Cancer Institute

18. Immunotherapy: Why don't more patients respond? | UChicago Medicine

19. Mechanisms of cancer resistance to immunotherapy (2020)

20. Aging of the immune system. Mechanisms and therapeutic targets (2016)

21. The prospect of immunotherapy combined with chemotherapy in patients with advanced non-small cell lung cancer: a narrative review (2021)

22. Cancer | World Health Organization

Victoria is a writer from the UK with a keen interest in health and science. She loves writing about mental health, scientific advancements, and dispelling pseudoscience. When she’s not writing sass-laden articles, she walks her rescue dogs, giggles at anxiety memes, eats chocolate, and absorbs useless knowledge for quiz shows.