Vaginal cancer pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Syed Musadiq Ali M.B.B.S.[2]

Overview

Vaginal cancer is a rare type of cancer that affects women. Vaginal intraepithelial neoplasia is a precancerous condition where some cells look abnormal. These cell changes are not cancer, but could become cancer over time. Vaginal intraepithelial neoplasia or VAIN means that the changed cells are only found in the innermost surface layer of the vagina. VAIN is more common in women who have had their uterus removed (hysterectomy) and in those who were treated for cervical cancer or pre-cancer in the past.

Pathophysiology

  • The vagina is a tube-like organ that connects the cervix (the lower part of the uterus) to the vulva (the outside female genitals).
  • The vagina is lined by a layer of flat cells called squamous cells.
  • This layer of cells is also called epithelium because it is formed by epithelial cells.
  • At birth, a baby passes through the vagina as he or she is born, so the vagina is sometimes also known as the birth canal.
  • Vaginal intraepithelial neoplasia is defined by the presence of squamous cell atypia without invasion.
  • The disease is classified according to the depth of epithelial involvement.
  • There are 3 types of VAIN: VAIN1, VAIN2, and VAIN3.
  • Low-grade VAIN (VAIN1) will sometimes go away on its own, but VAIN can sometimes lead to cancer if not treated.
  • Higher-grade VAIN (VAIN2 or VAIN3) is usually treated right away.
  • Two etiologies have been proposed to explain the strong association between VaIN and neoplasia elsewhere in the lower genital tract.
  • One possibility is that women who develop VaIN shortly after surgery for cervical intraepithelial neoplasia (CIN) may simply have vaginal extension of cervical disease that was not detected and treated.
  • VaIN is frequently multifocal, can occur several years after a hysterectomy for neoplasia, is independent of the amount of vaginal cuff excised, and is often observed de novo in the absence of cervical disease[1].
  • A second theory is that lower genital tract neoplasia share common etiologic factors, since approximately one-half of VaIN lesions are associated with concomitant cervical or vulvar neoplasia[2].
  • Tissues of common embryological origin are susceptible to neoplasia from exposure to similar carcinogenic stimuli. In particular, exposure to human papillomavirus (HPV) appears to induce neoplasms in all three locations of the lower female genital tract (cervix, vagina, vulva)[3].
  • HPV infection — HPV-associated lesions are often multifocal (originating within several discrete foci at one anatomic site) and multicentric (involving several distinct anatomic sites of the lower genital tract).
  • Although the relationship between HPV infection and intraepithelial neoplasia of the cervix is well known, there are less data available regarding vaginal neoplasia[4].
  • Several viral subtypes are associated with VaIN (table 1), with HPV 16 and 18 being the most prevalent HPV types [31]. The prevalence of oncogenic HPV subtypes in the vagina is similar in women who have and have not undergone hysterectomy[5].
  • Thus, presence of the cervix does not appear to be necessary for oncogenic HPV to infect the genital tract. (See "Cervical cancer screening tests: Techniques for cervical cytology and human papillomavirus testing", section on 'HPV testing'.)
  • The disparity between the relatively high incidence of CIN and rarity of VaIN in women who test positive for HPV may be due to increased susceptibility of the metaplastic transformation zone of the cervix to oncogenic stimuli. By contrast, the mature, stable, squamous epithelium of the vagina may be less vulnerable to the same stimuli[6].
  • Women who have been exposed to diethylstilbestrol (DES) in utero often have squamous metaplasia of the vagina instead of normal columnar epithelium; this observation may explain the increased incidence of VaIN noted in some studies of these women[7].
  • Women who have the human papillomavirus (HPV) are more likely than other women to develop this rare cancer.
  • Women who have been infected with herpes simplex virusare also at higher risk for vaginal cancer.
  • If a woman’s mother took a medicine called diethylstilbestrol (DES) when she was pregnant between 1940 and 1971.
  • Women whose mothers took DES – known as DES daughters – develop clear-cell adenocarcinomaof the vagina or cervix more often than women in the general population.
  • Lesions characteristically arise from the posterior wall of the upper third of the vagina. The common patterns of disease are:

References

  1. Creasman WT, Rutledge F (March 1972). "Carcinoma in situ of the cervix. An analysis of 861 patients". Obstet Gynecol. 39 (3): 373–80. PMID 5019309.
  2. Aho M, Vesterinen E, Meyer B, Purola E, Paavonen J (July 1991). "Natural history of vaginal intraepithelial neoplasia". Cancer. 68 (1): 195–7. PMID 2049744.
  3. Sturgeon SR, Curtis RE, Johnson K, Ries L, Brinton LA (March 1996). "Second primary cancers after vulvar and vaginal cancers". Am. J. Obstet. Gynecol. 174 (3): 929–33. PMID 8633671.
  4. Matsukura T, Sugase M (March 1995). "Identification of genital human papillomaviruses in cervical biopsy specimens: segregation of specific virus types in specific clinicopathologic lesions". Int. J. Cancer. 61 (1): 13–22. PMID 7705925.
  5. Castle PE, Schiffman M, Bratti MC, Hildesheim A, Herrero R, Hutchinson ML, Rodriguez AC, Wacholder S, Sherman ME, Kendall H, Viscidi RP, Jeronimo J, Schussler JE, Burk RD (August 2004). "A population-based study of vaginal human papillomavirus infection in hysterectomized women". J. Infect. Dis. 190 (3): 458–67. doi:10.1086/421916. PMID 15243917.
  6. Schneider A, de Villiers EM, Schneider V (September 1987). "Multifocal squamous neoplasia of the female genital tract: significance of human papillomavirus infection of the vagina after hysterectomy". Obstet Gynecol. 70 (3 Pt 1): 294–8. PMID 2819794.
  7. Bornstein J, Adam E, Adler-Storthz K, Kaufman RH (January 1988). "Development of cervical and vaginal squamous cell neoplasia as a late consequence of in utero exposure to diethylstilbestrol". Obstet Gynecol Surv. 43 (1): 15–21. PMID 2829071.