HPV Reactivation: Causes, Symptoms, and Implications

Human Papillomavirus (HPV) is a widespread virus that most people encounter during their lives. Following an initial infection, the immune system often controls the virus, causing it to become dormant and reside within the body’s cells without causing symptoms. However, under certain conditions, this latent virus can become active again, a process known as reactivation.

What is HPV Reactivation?

HPV reactivation occurs when a dormant, or latent, virus begins to actively replicate again. After an initial infection, HPV can enter a latent state where its DNA persists in the basal epithelial stem cells—the deepest layer of skin or mucosa. During this phase, which can last for months, years, or even decades, the virus is not causing disease and may be undetectable by standard HPV DNA tests due to the low number of viral copies.

Reactivation is distinct from acquiring a new HPV infection from an external source or a persistent infection, where the virus never becomes fully dormant but continues to replicate at low levels. The process is triggered when the host’s immune system is compromised, losing its ability to keep the latent virus in check. This allows the viral life cycle to resume.

When a basal stem cell with latent HPV divides, one new cell may begin to differentiate and move toward the skin’s surface. This differentiation signals the dormant virus to begin replication. As the cell matures, the reactivated virus uses its resources to produce new viral particles, which can cause clinical signs of infection or be shed from the body.

Factors Leading to HPV Reactivation

A weakened immune system is the primary trigger for HPV reactivation. Several factors can cause this immunosuppression:

• Medical conditions like Human Immunodeficiency Virus (HIV), which causes a decline in T-cell immunity.
• Immunosuppressive medications used by organ transplant recipients or patients with autoimmune diseases.
• The natural decline in immune function due to aging, a process known as immunosenescence.
• Significant hormonal fluctuations, such as those during pregnancy or menopause.
• Lifestyle choices, particularly smoking, which has known immunosuppressive effects.

Identifying Reactivated HPV Infections

A reactivated HPV infection may or may not produce noticeable symptoms. In some cases, reactivation leads to a clear recurrence of clinical signs. For individuals with low-risk HPV types, this could mean the reappearance of genital warts months or even years after a previous episode was successfully treated. For high-risk types, it might manifest as the development or progression of precancerous lesions on the cervix, anus, or in the oropharyngeal region.

Many reactivated infections are asymptomatic and are detected only through routine health screenings. For instance, a person who previously tested negative for a high-risk HPV type might test positive on a later test. This change can signal reactivation, especially if recent sexual activity is unlikely to explain a new infection.

A rise in viral load on a lab test can also indicate reactivation. However, it is challenging to prove reactivation definitively. It can be difficult to distinguish it from a persistent low-level infection or a new infection with the same HPV type. Therefore, clinicians assess the likelihood of reactivation using a combination of testing history, viral load data, and a person’s medical and sexual history.

Implications and Management of HPV Reactivation

The health consequences of HPV reactivation depend on the viral type involved. When low-risk HPV types reactivate, they can cause the recurrence of genital warts or benign growths like respiratory papillomatosis. While not cancerous, these conditions can require repeated treatments. The implications are more serious for high-risk HPV types, which are linked to several forms of cancer.

Reactivation of high-risk HPV can increase the likelihood of developing or advancing precancerous cellular changes. If left unmonitored and untreated, these changes can progress to invasive cancers of the cervix, anus, oropharynx, and other sites. The risk is elevated in individuals with compromised immune systems, who are more susceptible to persistent and aggressive infections following reactivation.

Regular screening, such as Pap and HPV tests for cervical cancer, allows for early detection of cellular changes from reactivated HPV. Individuals at higher risk for reactivation, like organ transplant recipients, may be advised to undergo more frequent screening. If clinical signs appear, prompt medical evaluation and treatment can manage the condition. While the HPV vaccine prevents initial infection, its ability to prevent the reactivation of a pre-existing latent infection is not established.