VAIN is uncommon, accounting for approximately 0.4% of lower genital tract intraepithelial disease but, like vulval intraepithelial neoplasia (VIN), has increased in recent years; it is now found in younger females and this rise seems to be associated with the increased prevalence of human papillomavirus (HPV) infections of the genital tract. Its incidence is estimated at 0.2/100 000 compared with the rate for cervical intraepithelial neoplasia (CIN) of 36.4/100 000.

There appear to be four populations of women who are at increased risk of developing VAIN.

The first, which forms the majority, is those women who have already undergone procedures to deal with a pre-existing cervical precancer (CIN). Treatment may have been in the form of a local conservative procedure, using laser, loop diathermy, or cryotherapy. It is estimated that up to 1–3% of patients with cervical neoplasia have either coexisting VAIN or will develop it at a later date. The time at which this will occur may be as short as 2 years or may extend up to 17 years. There also seems to be an increased risk of VAIN in those who have VIN.

The second population comprises those who have had radiation therapy for cervical cancer. This increased incidence of VAIN may take some 10–15 years to manifest itself after the initial radiation therapy; it has been suggested that the epithelium of the vagina may be sensitized by low-dose radiation for the subsequent development of neoplasia.

The third population consists of those who have had a hysterectomy as treatment for CIN, and in whom a vaginal abnormality is diagnosed during follow-up. About 70% of women with VAIN had undergone hysterectomy. This presentation was more common in the past, when relatively few patients had the advantage of a colposcopic assessment of their CIN before being treated by hysterectomy. In many cases, part of the pre-existing cervical lesion extended into the vaginal fornix and was not included in the surgical resection. Between 1% and 6% of cervical and vaginal (forniceal) intraepithelial lesions coexist, and in some 67% of them a confluence between the two areas is present. The incidence of VAIN 10 years after hysterectomy follow-up is 0.9%. It is in this area of abnormal (atypical) epithelium (with its extension of CIN) that the subsequent VAIN and invasive cancer would seem to develop.

The age range for those who may develop VAIN extends from 24 to 80 years, with a mean age estimated at around 50 years. In the younger age group there has been a marked increase in association with other epithelial lesions of the genital tract, and this may be related to the increased presence of HPV.

The fourth group consists of women who are immunosuppressed, either following renal or other transplants or idiopathically, or in association with human immunodeficiency virus infections.

The exact malignant potential of VAIN is still not known. It is assumed that VAIN progresses to invasive disease because of its similarity to intraepithelial disease of the cervix, but, unfortunately, it is difficult to determine either the number or the type of VAIN lesions that will indeed progress. The lifetime risk of malignant progression of VAIN has been reported at around 10% while more than three-fourths of VAIN lesions may regress back to normal.

Furthermore VAIN not associated with CIN or VIN tended to have a higher regression rate (91%) than those with accompanying CIN/VIN.

With the advent of the quadrivalent prophylactic vaccine against HPV-induced lower genital tract lesions, there is already evidence of efficacy of its ability to reduce the rate of VAIN lesions.

It has been assumed for many years that both cervical and vaginal neoplasias share a common etiology, although the direct evidence has been difficult to document. However, indirect evidence comes from a number of associations. The most notable is that vaginal and cervical neoplasias occur synchronously; that cervical cancer survivors have an increased risk of developing vaginal neoplasia as a second primary tumor and vice versa; and that HPVs, which are now recognized as the viral agents involved in the pathogenesis of cervical neoplasias, are present in vaginal tumor tissue. A multicenter case-controlled study of in situ and invasive vaginal carcinomas found that certain parameters of sexual behavior were only modestly related to vaginal cancer risk and that even in women who had reported five or more sexual partners in a lifetime the risk of disease was only 1.4-fold increased. An early age of first intercourse was not found to be associated, and this was surprising given the consistency in the association of these factors with cervical cancer causation. However, in that study, women who reported a history of sexually transmitted diseases, most commonly due to genital warts, were found to be at excess risk of vaginal tumors. It is believed that 70% of tumors are HPV induced, mostly as a result of HPV type 16.

VAIN following a hysterectomy for CIN is very uncommon; various authors quote between 1% and 3% as the prevalence of vaginal recurrence after hysterectomy when a similar lesion previously existed on the cervix. Some authors have quoted a higher frequency of 20% in patients previously treated for CIN. Although the long-term recurrence rate for VAIN is uncertain, it is suggested by many authors that incomplete excision of the vaginal cuff at the time of hysterectomy for CIN may explain these early recurrences. The presence of such a lesion in the vaginal cuff area before 1 year after hysterectomy often represents a failure to diagnose and treat the vaginal component of cervical disease at the time of primary treatment; in many cases, histologic examination of the original uterine specimen reveals disease at the excised surgical margins.

The neoplastic process can be present within pre-existing vaginal cuff inclusion cysts or sinuses. Any nodularity or distortion of the vaginal cuff found during hysterectomy must be treated by surgical excision, not only so as to treat the existing VAIN but also to exclude the presence of any occult invasive cancer within these lesions.

While most of these cases are diagnosed within a few years of surgery, a different pattern is seen in patients who have a history of previous radiotherapy. This raises the possibility that a sublethal dose of radiation, sufficient to cause cell damage but not cell death, may have been implicated in the etiology.

Preoperative colposcopy and staining of the upper vagina with Lugol’s iodine solution should demonstrate the extension of any abnormal (atypical) cervical epithelium onto the vaginal fornix. This will allow a surgeon performing hysterectomy for CIN to determine accurately the amount of vaginal cuff to remove, whether the operation be by the abdominal or by the more preferable vaginal or laparoscopic approach. Indeed, hysterectomy as a treatment for CIN is nowadays uncommon. Figure 8.9a shows a diagrammatic representation of the failure to evaluate preoperatively the extent of CIN. The vaginal angle clamp can be seen applied across an area of CIN that extends into the right vaginal fornix; obviously this extension had not been fully recognized preoperatively. The result is that residual disease is retained postoperatively in the angle of the vagina (Figure 8.9b). These angle clamps should be ligated, the vaginal vault can be left open, and mattress sutures should be avoided in the resuturing of the vault. Hemostasis is obtained by simply oversewing the vaginal edges. No prospective trial to evaluate the efficacy of this procedure has been undertaken.

Once the patient has been examined and the lesion defined, it is important to take a biopsy in order to produce tissue confirmation. From time to time in the patient who has had a previous hysterectomy and is postmenopausal, it will be difficult to gain access to the upper vagina. The use of acetic acid or iodine may produce further considerable discomfort to the patient because of the thinness and atrophic change in the vaginal skin. It is often worthwhile for the patient to use estrogen cream for 2–4 weeks before returning to the colposcopy clinic for a re-examination; by this time the vaginal skin will have markedly thickened. Sometimes, minor epithelial abnormalities will have disappeared and the major-grade VAIN lesions will be much easier to identify confidently and biopsy.

In the postmenopausal woman it may be extremely difficult to obtain an adequate cytologic sample of the vaginal vault epithelium because of marked atrophic changes; attempts to procure an adequate smear from this dry surface may induce bleeding, further obscuring and interfering with the cytologic specimen. In these cases, it is imperative to use estrogens in the form of cream instilled high into the vagina so that, after a few weeks, it will be possible and easier to obtain a satisfactory smear, and also to procure a punch biopsy.