Current Update on the Treatment of Genital Warts

Valerie R Yanofsky; Rita V Linkner; David Pompei; Gary Goldenberg


Expert Rev Dermatol. 2013;8(3):321-332. 

In This Article

HPV Malignancy

Malignancy is typically associated with high-risk types of HPV, especially with types 6 and 11; however, low-risk type association has been observed. Verrucous carcinoma (VC), a low-grade, well-differentiated form of SCC, is believed to be associated with both high- and low-risk genotypes.[26] VC can be divided into three distinct clinicopathologic types based on anatomic area of involvement: oral florid papillomatosis (oral cavity), giant condyloma of Buschke and Löwenstein (anogenital area), and carcinoma cuniculatum (palmoplantar surface). These tumors rarely metastasize, typically spreading through local invasion.[27] While the authors are yet to establish a direct causal relationship between HPV and VC, persistent HPV infection and viral oncogene expression is known to promote the degradation of the p53 tumor suppression gene, which may result in a lower threshold for tumor formation.[28]

VC can vary in histopathologic appearance from benign lesions resembling pseudoepitheliomatous hyperplasia to VCs that are virtually indistinguishable from invasive SCC. Characteristic features of genital warts, such as vacuolation and prominent keratohyalin granules in the stratum granulosa, are not always detectable.[29,30] For more ambiguous lesions, VC and SCC may be differentiated based upon their immunoperoxidase staining pattern – more specifically, staining samples with p53 and Ki-67 will target the nuclei of basal proliferating cells, which are located predominantly in the lower third of the epidermis in VC. This can be contrasted with the staining pattern of SCC, which will be positive for these same markers throughout the full thickness of the epidermis.[31]

A further complication of HPV infections, as mentioned previously, is the increased risk for malignant progression, especially cervical dysplasia and a long-term risk of invasive cancer.[32] While most HPV infections will ultimately clear spontaneously, one-third of EGW harbor high-risk HPV[4] and 10–20% of exposed women will develop persistent oncogenic infections that are associated with a greater risk of progression to cervical intraepithelial neoplasm (CIN) grade II/III. These are thought to be precancerous lesions, which, if left untreated, may eventually give rise to invasive cervical cancer.[33] Penile cancer, which is less common, has shown a strong correlation to both high-risk HPV infection and a history of persistent EGW. This is evidenced by a case–control study involving over 100 men with penile cancer, which identified the risk of penile cancer to be 5.9-times higher in men with a history of EGW when compared with those without (95% CI: 2.1–17.6).[34]