The Impact of Focality and Centricity on Vulvar Intraepithelial Neoplasia on Disease Progression in HIV+ Patients: A 10-Year Retrospective Study

Abstract

Background: The impact of lesion focality and centricity in relation to patient outcome and disease recurrence of vulvar intraepithelial neoplasia (VIN) is an understudied area of research, especially in immunocompromised women. The prevalence and incidence of VIN have increased steadily since the 1980s because of the co-existence of human papillomavirus (HPV) and human immunodeficiency virus (HIV). In this study, we retrospectively examined the records of VIN patients to determine the effect of lesion focality and centricity with respect to the interval to disease recurrence. Materials and Methods: All women diagnosed with VIN and managed between January 2002 and December 2011 were included (n = 90) and followed up until December 2017. Symptoms at the time of presentation, including HIV positivity (n = 75), were collated, including the influences of multifocality and multicentricity on time to disease recurrence. Results: Multicentricity caused a more rapid recurrence of disease than unicentricity (p = 0.006), whereas multifocality increased the risk of recurrence more than unifocality (p < 0.0001). Viral load in the HIV+ patients was not associated with time to disease recurrence, but the reduced number of CD4+ lymphocytes present in HIV+ patients was. Treatment modalities had no effect on disease recurrence. Conclusion: Both focality and centricity have effects on interval to recurrence and final patient outcome, with multifocal disease having a poorer prognosis. Centricity and focality should be recorded at the time of diagnosis and act as a warning for disease recurrence. HIV+ VIN patients with multifocal disease and/or known immunosuppression (low CD4+ lymphocyte counts) should be regarded as “high-risk” patients and treated accordingly.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD) and the European Federation for Colposcopy (EFC) Consensus Statements on Pre-invasive Vulvar Lesions

“…162,163 HIV-infected women have higher incidence rates of VIN at a younger age and frequently have multifocal and multicentric HPVrelated lesions. 101,110,[164][165][166][167] Indeed high-grade cervico-vaginal cytology was reported following treatment for VIN or vulvar cancer with OR 3.4 for immunodeficiency (95% CI 1.3 to 8.8). 135 The recurrence and progression rates are far higher and with a shorter disease-free interval for HIV+ women than HIV− women, 101,165 with a lower CD4 + lymphocyte count linked to shorter time to recurrence.…”

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD) and the European Federation for Colposcopy (EFC) consensus statements on pre-invasive vulvar lesions

“…HIV-infected women have higher incidence rates of VIN at a younger age and frequently have multifocal and multicentric HPV-related lesions 98 107 161–164. Indeed high-grade cervico-vaginal cytology was reported following treatment for VIN or vulvar cancer with OR 3.4 for immunodeficiency (95% CI 1.3 to 8.8) 132…”

“…The recurrence and progression rates are far higher and with a shorter disease-free interval for HIV+ women than HIV− women,98 162 with a lower CD4 +lymphocyte count linked to shorter time to recurrence 107 162. Highly active antiretroviral therapy may decrease the incidence of condyloma and LSIL but appears to have no impact on VHSIL 165–167…”

A Systematic Review of Risk Factors for Development, Recurrence, and Progression of Vulvar Intraepithelial Neoplasia

“…Multifocal lesions, multicentric disease, and immunosuppression (including HIV+) were the most commonly cited clinical risk factors for VIN recurrence. The most commonly reported <.0001 37 Unifocal lesion 30%, 22 39.2%, 19 16.7%, 13 30%, 20 34.2% 13,18,20,24,29,34 versus 4.3% to 24.3% 13,18,20,24,29,34 for negative margins. The most significant risk factor for recurrence was p53 overexpression (81.8% 23 recurrence rate) and adjacent lichen sclerosus (OR = 9.91).…”