New and Surprising Insights Into Pathogenesis of Multicentric Squamous Cancers in the Female Lower Genital Tract

Abstract

Infection with high-risk types of human papillomavirus (HR-HPV) is extremely common in the cervix, vagina, and vulva; and women with persistent HR-HPV infections at these sites have been shown to be at increased risk for the development of invasive squamous cell cancers at these locations ( 1 – 3 ) . Prior to the establishment of routine cervical cancer screening, invasive cervical cancer was among the most common causes of cancer mortality in women. Compared with cervical cancer, vaginal and vulvar cancers develop infrequently (current age-adjusted incidences of cervical, vaginal, and vulvar cancers = 8.9/100 000 women per year, 0.7/100 000 women per year, and 2.3/100 000 women per year, respectively) ( 4 ) . Previous studies (e.g., [5,6] ) have shown that a history of a prior cervical neoplasm (cervical intraepithelial neoplasia grade 3 [CIN 3] or invasive cervical cancer) is an important risk factor for the development of vaginal and vulvar cancers. The most likely explanation for this association is that women who develop cervical neoplasia frequently are infected with HR-HPV both at the cervix and in the vagina and vulva, and they occasionally develop a second independent neoplasm at the last two sites. Other explanations for this association between a history of a prior cervical neoplasm and the later development of a vaginal or vulvar cancer include recurrence of the original cervical cancer at the surgical margin after hysterectomy and development of a second primary neoplasm in the vagina or vulva as a result of radiation therapy for treatment of the original cervical neoplasm.