What virus is associated with Kaposi (Kaposi's) sarcoma: Herpes Simplex Virus (HSV), Herpes Zoster Virus (HZV), or Human Papillomavirus (HPV)?

Kaposi Sarcoma is Associated with Human Herpesvirus 8 (HHV-8)

Kaposi sarcoma is universally associated with Human Herpesvirus 8 (HHV-8), also known as Kaposi sarcoma-associated herpesvirus (KSHV), and not with Herpes Simplex Virus, Herpes Zoster Virus, or HPV. 1

Viral Association and Pathogenesis

HHV-8 is a gamma-2 herpesvirus (rhadinovirus) that was discovered in 1994 and has been consistently implicated in all epidemiologic forms of Kaposi sarcoma. Serologic confirmation of HHV-8 infection is present in 95%-98% of patients with Kaposi sarcoma, making it the definitive causative agent. 1

The virus works through several mechanisms:

• HHV-8 contains multiple oncogenic viral genes that directly promote cell survival and transformation
• It encodes homologues of cellular genes that regulate cell growth and differentiation
• Immunosuppression is a critical cofactor in the pathogenesis of Kaposi sarcoma in HHV-8-infected individuals 1

Epidemiology and Clinical Forms

Four distinct clinical-epidemiological forms of Kaposi sarcoma exist:

1. Classic KS: Indolent cutaneous lesions, often of the lower extremities, common in older people of Mediterranean, Eastern European, Middle Eastern, and Jewish origins

2. Endemic KS: Occurs in children and younger adults in equatorial Africa, more aggressive than classic KS

3. Iatrogenic/Transplant-associated KS: Occurs in the context of immunosuppressive therapy, often responds to reduction of immunosuppression

4. AIDS-related/Epidemic KS: Occurs in HIV-positive individuals, considered an AIDS-defining illness, tends to be more aggressive than other types 1

HIV Association and Risk

The risk for Kaposi sarcoma in people living with HIV has been reported to be increased as much as 3,640-fold over the general population, though this risk has declined in the antiretroviral therapy (ART) era. 1

In HIV-infected individuals:

• CD4+ T-cell counts and HIV viral load correlate with the risk of Kaposi sarcoma
• When immunosuppression is advanced, AIDS-related Kaposi sarcoma is more common and more aggressive
• However, AIDS-related Kaposi sarcoma can occur in people living with HIV who have normal CD4+ T-cell counts and viral load 1

Diagnostic Considerations

The diagnosis of Kaposi sarcoma is based on:

• Pathology and immunophenotyping
• Latency-associated nuclear antigen (LANA) of HHV-8 is the most specific immunohistochemical marker available to distinguish KS from mimics
• Clinical presentation with characteristic red or brown papules, often at mucocutaneous sites 1, 2

Clinical Significance

Understanding the viral etiology of Kaposi sarcoma is critical for:

1. Accurate diagnosis and differentiation from mimics
2. Risk stratification in immunocompromised patients
3. Development of targeted therapies
4. Prevention strategies in high-risk populations

The 5-year survival rate for patients with AIDS-related Kaposi sarcoma has improved significantly in the post-ART era, from 12.1% in 1980-1995 to as high as 88% currently, highlighting the importance of immune reconstitution in controlling HHV-8-associated disease. 1