Diagnoses of primary vaginal carcinoma must satisfy the International Federation of Gynecology and Obstetrics (FIGO) criteria, including sparing of the uterine cervix. According to these criteria, vaginal carcinoma is rare and affects older women aged greater than 60 years. The posterior wall of the upper third of the vagina is the most frequently involved site [61]. Coexistence of vaginal intraepithelial neoplasia (VAIN) and vaginal carcinoma is rare, comprising 0.4 % of all intraepithelial neoplasia affecting the lower female genital tract. VAIN has been shown to be associated with high-risk human papillomavirus (HPV) infection, with cervical intraepithelial neoplasia (CIN) seen in up to 43 % of women [62–65]. VAIN reportedly occurs in the presence of multiple HPV-associated lesions affecting the lower genital anogenital tract. The natural history of VAIN is thought to be largely similar to that of CIN with high-grade VAIN considered a precancerous lesion [62, 66]. Although a three-tier system stratifying vaginal intraepithelial neoplasia into VAIN1, VAIN2, and VAIN3 categories has been previously widely used in clinical management, a two-tier system categorizing vaginal intraepithelial neoplasia as either LSIL or HSIL has recently been proposed and adopted in the newly released 2014 WHO classification [67]. It is, henceforth, anticipated that the new two-tier system will be adopted in the clinical management of VAIN.

Vaginal SILs are commonly asymptomatic. Cytologic screening is the conventional method of identifying the presence of vaginal SIL. The vagina should be carefully inspected by colposcopy for obvious abnormalities, with particular attention paid to the upper vagina. Vaginal HSIL commonly involves the upper third of the vagina or the vaginal vault following hysterectomy and is frequently multifocal involving other regions of the lower genital tract, termed “lower genital tract neoplastic syndrome ” (Fig. 14.5). Colposcopic examination and directed biopsy are the mainstays of accurate vaginal HSIL diagnosis. In typical colposcopic findings, vaginal HSILs are ovoid and slightly raised, exhibiting a thickened acetowhite epithelium and a raised external border. Lesions with a papillary surface or abnormal vascular patterns, such as punctuation or mosaic, should be examined by multiple biopsies to rule out invasive carcinoma [61] (Fig. 14.5). Colposcopy is often a poorer predictor of histological findings in vaginal SIL than in cervical SIL. Even in cases where colposcopy reveals mild and atrophic changes, histologic findings occasionally demonstrate more severe changes (Fig. 14.6).

Evidence regarding the optimal clinical management of HSIL is lacking. Empirical practices include surgical excision or ablation of suspicious areas [68, 69]. Conservative surveillance in selected populations has been reported previously; however, the efficacy and safety of these approaches is not well known [65]. Renavelu et al. suggested the following limitations frequently apply to HSIL studies: (a) clear definitions of “remission” and “recurrence” are lacking; (b) the majority of case series are smaller; (c) those of comparable size date back 10 years; (d) previous papers report a mixed series of LSIL and HSIL; and of particular note, (e) the role of abnormal cytology as a preclinical indicator of disease recurrence has not previously been established among women posttreatment [65].

Local excision is the main therapeutic approach for vaginal HSIL. Ideally, local excision of a small and isolated area is performed under local anesthesia. Excision of large or multiple areas can be performed under general anesthesia. When lesions involve the upper area or vaginal vault following hysterectomy, upper colpectomy may be appropriate. Alternatively, total colpectomy followed by vaginal restoration with a split-thickness skin graft may be considered. However, major surgery carries a risk of bladder and/or bowel fistula formation or shortening and narrowing of the vagina. Therefore, aggressive surgical procedures are considered inappropriate for the treatment of HSIL.

CO₂ laser vaporization is an efficient treatment of histologically proven lesions with the absence of invasive carcinoma confirmed cytologically and colposcopically that may performed under local or general anesthesia [71]. Prior to vaporization, the lesion is injected with mixture of saline and anesthetic or saline alone that acts as a necessary protective buffer that prevents penetration to deeper tissues. Vaginal HSIL can be effectively treated by CO₂ laser vaporization to a depth of 1.5 mm, sufficient for the destruction of epithelium containing vaginal SIL without damaging surrounding structures [71, 72]. Cavitational ultrasonic surgical aspiration (CUSA) may be effective and safe for the treatment of VAIN. CUSA allows selective removal of diseased tissue with minimal damage to surrounding healthy tissue [74, 75].

Topical application of 5-fluorouracil (5-FU) cream has been advocated by a varying proportion of investigators over the last three decades and was most frequently employed in the 1980s [61]. Vaginal burning with ulceration and vaginal bleeding, occasionally requiring surgery, are common complications of topical 5-FU administration. Combination therapy consisting of laser vaporization and 5-FU treatment may be preferred for the treatment of multifocal lesions, particularly in post-hysterectomy cases with deep vaginal angles [76]. Different treatment schedules and dose levels have been investigated to identify regimens that maintain efficacy while decreasing adverse effects. Some investigators have advocated surface irradiation as brachytherapy using an intravaginal applicator [77–79]. However, brachytherapy is associated with risk of recurrence and marked vaginal stenosis, increasing the difficulty of subsequent therapies [61]. A recent cohort study reported high rates of regression and cure of vaginal HSIL in patients treated with intravaginal estrogen alone or in combination with other treatment modalities. This treatment may represent a viable alternative therapy [80].

The incidence of vulvar intraepithelial neoplasia (VIN) is increasing in women under 50 years of age [81]. The rising prevalence of human papillomavirus infection (HPV) has led to a continuously increasing incidence of VIN and vulvar carcinoma [82–84]. In 1986, the International Society for the Study of Vulvar Disease (ISSVD) introduced the term, VIN , to designate precursors of vulvar squamous cell carcinoma. Although VIN was initially considered a single category, strong evidence has subsequently accumulated over the last two decades indicating the existence of at least two distinct clinicopathologic subtypes, one associated with high-risk HPV infection and a second independent of HPV infection. In 2004, the ISSVD proposed a classification system reflecting these two subtypes: HPV-associated usual VIN (uVIN) and HPV-independent differentiated VIN (dVIN) . Following this proposal, dVIN is considered a clinical distinct entity from uVIN. The natural history of uVIN is thought to be similar to that of cervical intraepithelial neoplasia (CIN) with high-grade uVIN considered a precancerous lesion [85]. The three-tier classification system has previously been used in the clinical management of VIN, but there has been renewed interest in the use of the two-tiered squamous epithelial lesion stratification system describing low-grade SIL (LSIL) and high-grade SIL (HSIL), nomenclature that more accurately reflects the similar natural history of uVIN to other lower anogenital tract HPV-associated intraepithelial lesions. The two-tiered squamous epithelial lesion stratification system for uVIN and use of the term dVIN were recently adopted in the newly released 2014 WHO classifications [86].

Vulvar HSIL has a diverse clinical presentation. Nonspecific symptoms , including pruritus, irritation, and pain, are observed in approximately 60 % of cases. In younger patients, symptoms are often preceded or accompanied by condylomas. Since patients commonly present asymptotically or with nonspecific symptoms, accurate vulvar inspection during routine gynecologic examination is important. Vulvar lesions may be red, white, or pigmented in color and either flat or raised and may coexist with erosions or ulcers [85, 87, 88]. These findings should prompt further vulvar examination using a magnification instrument such as a colposcope. The use of acetic acid is not recommended as it is nonspecific for vulvar HSIL [89]. Biopsy of the most suspicious part of the lesion should be performed under local anesthesia to confirm diagnosis. The diagnosis of vulvar HSIL is made from the clinical appearance and subsequent biopsy findings. Unifocal lesions are most commonly observed around the vaginal introitus. Perianal skin is involved in 10–15 % of the patients with vulvar HSIL [89].

The considerable temporal difference of 20–30 years between the peak incidence of vulvar HSIL and invasive vulvar carcinoma suggests that there may not always be a causal link between these two conditions [90, 91]. The risk of progression to invasive carcinoma in vulvar HSIL is considered to be low [88, 92, 93]. Further, vulvar HSIL is commonly multifocal, whereas invasive vulvar carcinoma is most frequently unifocal. The behavior of vulvar HSIL is not apparently comparable to that of cervical HSIL. Spontaneously regressing vulvar HSIL, so-called bowenoid papulosis [94], characterized by small, multifocal, papular, and hyperpigmented lesions affecting the labia majora and/or perianal skin is known to occur in younger women (Fig. 14.8). The high rate of regression has been reported in patients under 30 years and has been shown to be particularly common in pregnant women [92, 95].

Despite the fact that dVIN was first described in the 1960s by Abell as a highly differentiated form of vulvar carcinoma in situ, until more recently, the pathological entity had not gained wide attention because its existence had clinically been questioned [96, 97]. Recent knowledge has revealed that dVIN is often observed in areas of lichen sclerosus in older women [97, 98]. It is estimated that dVIN accounts for a small proportion with up to 5 % of all VIN lesions compared with uVIN [99, 100]. White or red lesions in areas of hyperkeratosis, ulceration, and the presence of a rough and irregular surface are all suspicious for dVIN (Fig. 14.9). Patients are often symptomatic with a long history of lichen sclerosus of vulvar itching and/or burning, and dVIN diagnosis might be frequently missed. Due to the highly malignant potential of dVIN, non-healing ulcers and/or newly developed white hyperkeratotic lesions in patients with lichen sclerosus should be periodically biopsied or excised without delay to obtain a representative histopathological diagnosis [91]. It should be emphasized that the recognition of dVIN in patients with lichen sclerosus can be extremely challenging owing to associated ulceration and fissuring [85].