Will Human Papillomavirus (HPV) be cleared in men who have sex with men (MSM)?

Clearance of Anal HPV in Men Who Have Sex with Men

Most anal HPV infections in MSM will clear spontaneously over time, though clearance rates vary by HPV type, with HPV16 showing the lowest clearance rate among high-risk types. 1

Natural History of Anal HPV Infection in MSM

• HPV is associated with approximately 90% of anal squamous cell cancers, with men who have sex with men (MSM) having a significantly higher risk of HPV infection and HPV-related disease compared to heterosexual men 2
• The incidence of anal neoplasia is nearly 20 times higher in MSM than in the general population, with annual recurrence rates of high-grade anal lesions following treatment reaching up to 50% 2
• Most HPV infections are asymptomatic and clear spontaneously without causing health problems, though some progress to genital warts, precancers, and cancers 3

Clearance Rates

• Clearance rates for any HPV and high-risk HPV (Hr-HPV) in HIV-negative MSM are approximately 50.9 and 62.1 per 1,000 person-months, respectively 4
• The median duration of anal HPV infection in HIV-negative MSM ranges from 8.5 to 9.7 months for any HPV type 4
• HPV16 demonstrates the lowest clearance rate among carcinogenic types (approximately 59.7 per 1,000 person-months) and the longest duration of infection (approximately 16.8 months) 5
• In a 5-year prospective study, clearance rates of incident anal high-risk HPV infections had a median of 53.7 per 100 person-years across different types, with HPV16 having the lowest clearance rate 1

Incidence Rates

• Incidence rates for any HPV and high-risk HPV in HIV-negative MSM are approximately 53.4 and 39.0 per 1,000 person-months, respectively 4
• HPV16 has been shown to have the highest incidence rate among high-risk types in several studies 6, 1
• The combination of high incidence and low clearance rates for HPV16 is consistent with its predominant role in anal cancer cases 1

Factors Affecting HPV Clearance in MSM

• Sexual behaviors significantly impact both acquisition and clearance of anal HPV:

  • Receptive anal sex is a significant risk factor for acquiring any HPV (HR = 1.66) and Hr-HPV infection (HR = 1.99) 4
  • Both insertive and receptive anal sex (HR = 0.60) and frequent anal sex (≥2 times per week) (HR = 0.61) are associated with reduced Hr-HPV clearance 4
  • Recent anal sex without condom use is significantly associated with any HPV (HR = 1.80) and Hr-HPV infection (HR = 2.60) 4

• Age may play a role in HPV acquisition and clearance:

  • Age ≥35 years is significantly associated with low-risk HPV infection (HR = 1.40) 4
  • Higher incidence rates have been observed among younger MSM in some studies 6

• Immune response:

  • Antibody responses following anal HPV infection vary by HPV type, with types 6/11 more likely to induce seroconversion than types 16/18 (73% vs. 18%) 7
  • The median time between incident anal HPV infection and seroconversion varies by type: 91 days for HPV6, 38 days for HPV11, 161 days for HPV16, and 182 days for HPV18 7

Prevention and Management Implications

• HPV vaccination is strongly recommended for MSM aged 9-26 years due to high incidence and low clearance rates of anal HPV 2
• MSM aged 26 years and older may also benefit from HPV vaccination, though the evidence quality is lower 2
• Quadrivalent or nonavalent vaccines are preferred for MSM given the high prevalence of anogenital warts in this population 2
• The quadrivalent HPV vaccine has shown efficacy in preventing 77.5% of high-grade squamous intraepithelial lesions/anal intraepithelial neoplasia secondary to HPV 6,11,16, or 18, and 70.2% of genital warts in MSM 2
• In MSM aged 26 years and older, the quadrivalent vaccine has demonstrated effectiveness in preventing anal condyloma and reducing the incidence of high-grade squamous intraepithelial lesions 2

Clinical Considerations

• No national recommendations exist for cytologic screening to prevent anal cancers, despite the high risk in MSM 2
• Data are insufficient to recommend routine anal cancer screening with anal cytology in HIV-negative MSM, though an annual digital anorectal examination may be useful for early detection of anal cancer 2
• Anal intraepithelial neoplasia (AIN) is recognized as a precursor of anal cancer, although the natural history of these lesions is less clear than for cervical intraepithelial neoplasia 2
• Treatment options for anal HPV-related lesions include various local approaches that remove the lesion (e.g., cryotherapy, electrocautery, laser therapy, and surgical excision) 2

Human Papillomavirus infection in MSM follows a pattern of acquisition, persistence, and eventual clearance in most cases, though certain high-risk types (particularly HPV16) demonstrate longer persistence and lower clearance rates, explaining their predominant role in anal cancer development.