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Vaginal intraepithelial neoplasia

Vaginal intraepithelial neoplasia
Literature review current through: Jan 2024.
This topic last updated: Apr 22, 2022.

INTRODUCTION — The diagnosis of vaginal intraepithelial neoplasia (VaIN) has increased steadily over the past several decades as a result of heightened awareness, expanded cytologic and human papillomavirus screening, and the liberal use of colposcopy. The relative rarity of VaIN, which is far less common than vulvar intraepithelial neoplasia (VIN) or cervical intraepithelial neoplasia (CIN), is an impediment to a thorough understanding of the disease process and its natural course. As a result, much of this information is an extrapolation of our knowledge of the pathophysiology of VIN and CIN.

Diagnosis and management of patients with VaIN are reviewed here. VIN and CIN are discussed separately. (See "Vulvar squamous intraepithelial lesions (vulvar intraepithelial neoplasia)" and "Cervical intraepithelial neoplasia: Management" and "Cervical intraepithelial neoplasia: Choosing excision versus ablation, and prognosis and follow-up after treatment".)

CLASSIFICATION — VaIN is defined by the presence of squamous cell atypia without invasion. The disease is classified according to the depth of epithelial involvement:

VaIN 1 and 2 involve the lower one-third and two-thirds of the epithelium, respectively (picture 1).

VaIN 3 involves more than two-thirds of the epithelium.

Carcinoma in situ, which encompasses the full thickness of the epithelium, is included under VaIN 3.

In 2012, as part of the Lower Anogenital Squamous Terminology (LAST) Standardization Project for human papillomavirus-associated lesions, the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology (ASCCP) proposed a revised terminology by which VaIN is reported using a two-tiered nomenclature: vaginal low-grade squamous intraepithelial lesion (LSIL) for low-grade disease (VaIN 1) and vaginal high-grade squamous intraepithelial lesion (HSIL) for high-grade disease (VaIN 3) [1]. VaIN 2 is an intermediate lesion that is usually reclassified as either VaIN 1 or VaIN 3 on pathology review.

While clinically we often refer to VaIN using the LAST terminology, this topic will utilize the VaIN 1, 2, and 3 terminology as most studies present their data in this format.

EPIDEMIOLOGY — The true incidence of VaIN is unknown but is estimated at 0.2 to 0.3 cases per 100,000 females in the United States [2]. The average patient is between 43 and 60 years of age [3-5].

The incidence of vaginal carcinoma in situ (a subset of VaIN 3, as discussed above) is estimated at 0.1 cases per 100,000 females in the United States and peaks between the ages of 70 to 79 years, slightly younger than the peak incidence age for vaginal carcinoma [6].

In patients who undergo hysterectomy for cervical intraepithelial neoplasia, the incidence of subsequently developing VaIN 2+ is as high as 7.4 percent [7]. (See 'Classification' above.)

RISK FACTORS, PATHOGENESIS, AND PREVENTION

Human papillomavirus — Human papillomavirus (HPV) is the most common cause of VaIN [3]. Most VaIN 3 lesions are associated with at least one high-risk HPV subtype (table 1), with HPV 16 and 18 being the most prevalent subtypes [8-10].

A review of 232 published VaIN cases reported the following prevalence of HPV: 99 percent in VaIN 1 and 93 percent in VaIN 2,3 [11]. A worldwide collaborative found a similarly high prevalence of HPV in VaIN 2,3 (96 percent) [8].

VaIN is consistently associated with prior or concurrent neoplasia elsewhere in the lower genital tract. Because 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), up to 50 to 90 percent of patients with VaIN had or currently have either intraepithelial neoplasia or carcinoma of the cervix, vulva, anus, or perianal region [4,12-16].

Patients 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. However, VaIN is frequently multifocal, can occur 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 [7,17-22]. Approximately 1 to 7 percent of patients undergoing hysterectomy for CIN develop VaIN a few months to several years after surgery [7,18-20,23]. For example, one study found VaIN in 5 percent of 793 patients followed for 10 years after surgery for CIN 3 [21], and another study found the average time to diagnosis of VaIN after hysterectomy in patients with benign disease was 11 years, compared with 1 year among patients with CIN [22]. Thus, it is unlikely that VaIN is the result of extension from the cervix in every case.

Similarly, patients treated for vulvar neoplasia are at high risk of developing VaIN. In one retrospective study including 302 patients who underwent surgery for vulvar intraepithelial neoplasia (VIN) or cancer and followed for 72 months (median), abnormal cervical/vaginal cytology was present in 25 percent of patients and VaIN 2+ developed in 9 percent of patients [24]. Risk factors on multivariate analysis included prior abnormal cytology (odds ratio [OR] 3.4, 95% CI 1.6-7.6) and immunodeficiency (OR 3.4, 95% CI 1.3-8.8).

The disparity between the relatively high incidence of CIN and rarity of VaIN in patients 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 [25]. Patients who have been exposed to diethylstilbestrol (DES) in utero often have squamous metaplasia of the vagina; this observation may explain the increased incidence of VaIN noted in some studies of these patients [26,27]. However, these patients are also at risk for atypical vaginal adenosis and DES-associated clear cell adenocarcinoma, which are separate entities from VaIN and are discussed elsewhere. (See "Outcome and follow-up of diethylstilbestrol (DES) exposed individuals", section on 'Females exposed to DES in utero (DES daughters)'.)

The prevalence of oncogenic HPV subtypes in the vagina is similar in patients who have and have not undergone hysterectomy [28]. Thus, presence of the cervix does not appear to be necessary for oncogenic HPV to infect the genital tract. In fact, subsequent occult vaginal invasion appears to be more common in patients with CIN treated with hysterectomy than in those whose cervix was retained [22]. This may be the result of lower rates of follow-up cytology and more difficult examination of the vaginal apex in hysterectomized patients. It may also be a result of selection bias since only patients with no cervical dysplasia are likely to have their cervix retained.

Low levels of education, low family income, and history of vaginal condyloma have all been identified as risk factors for developing VaIN; however, all of these factors are also dependent variables predicting exposure to HPV [29].

HPV vaccination could potentially prevent approximately 70 percent of VaIN cases [30,31]. In one cohort study including over 500,000 female patients ages 17 to 26 years, HPV-vaccinated patients (82 percent) had lower rates of VaIN 3 or worse compared with HPV-unvaccinated patients (adjusted hazard ratio 0.30, 95% CI 0.13-0.68); the cumulative incidence of disease, however, was low [32]. (See "Human papillomavirus vaccination".)

Other risk factors

Immunodeficiency – VaIN is more common in patients with genetic and acquired immunosuppression, including HIV infection [33-35]. This is discussed in detail elsewhere. (See "Vulvar and vaginal intraepithelial neoplasia in patients with HIV infection".)

Cigarette smoking – Some data suggest an increased risk for VaIN 2,3 in high-risk HPV-positive patients who smoke compared with high-risk HPV-positive nonsmokers [36]. Smoking cessation is recommended to decrease the likelihood of VaIN.

The data regarding the role of previous radiation treatment in the development of secondary neoplasia of the vagina are conflicting [37,38].

NATURAL HISTORY — The natural course of VaIN has not been fully characterized. Although there have been no prospective studies, several retrospective investigations of various treatment modalities of VaIN have reported that 2 to 8 percent of cases of VaIN progress to invasive vaginal carcinoma [12-14,39-43].

One study, as an example, found that 9 of 32 patients undergoing vaginectomy for VaIN 3 had foci of invasive carcinoma upon histologic examination [39]. In another study, among patients with VaIN 3 who underwent excisional therapy, 4 of 39 (10 percent) were found to have vaginal carcinoma [44]. In another series, 18 of 23 patients with VaIN followed expectantly for at least three years had complete regression of their lesions, three patients had persistent disease, and two (one with VaIN 3 and another with a lower grade lesion) progressed to invasive carcinoma resulting in an estimated lifetime risk of malignant transformation of VaIN to invasive vaginal carcinoma of 9 to 10 percent [12].

CLINICAL PRESENTATION — VaIN is usually asymptomatic, although patients can present with postcoital spotting or vaginal discharge. It should be excluded in all patients with an abnormal Pap smear who are posthysterectomy or who do not have identifiable cervical lesions that could account for the abnormality.

DIAGNOSTIC EVALUATION — The following components are part of the diagnostic evaluation for patients with suspected VaIN.

Physical examination — A gynecologic examination should be performed, with thorough inspection and palpation of the vagina for lesions, color changes, ulceration, and thickening or irregularity of the vaginal wall. The majority of VaIN lesions are located in the upper one-third of the vagina, and multiple lesions occur in over 50 percent of patients [45,46].

Colposcopy — A thorough colposcopic assessment of the entire vagina should be performed for any patient with the above physical examination findings.

After the insertion of a speculum and the application of acetic acid, VaIN lesions will appear as raised or flat white, granular epithelium with sharply demarcated borders and may contain areas of vascular punctation. Lesions located in posthysterectomy vaginal recesses can be difficult to visualize; skin hooks may be used to gently evert these areas. The presence of a markedly irregular surface or severe vascular abnormalities with unusual branching suggests an invasive process, which warrants an excisional biopsy. Schiller or Lugol iodine solution can be used to detect lesions and confirm boundaries prior to excision.

In the postmenopausal patient, a few weeks of topical estrogen treatment will often accentuate visualization and improve detection of VaIN.

Biopsy technique — The planned biopsy site is prepared with iodine or 4% chlorhexidine. Local anesthetic is injected (eg, 1 percent lidocaine without epinephrine). When a biopsy is attempted, it is helpful to partially close the speculum to allow the vagina to fold in on itself. Keeping the vagina taut makes performing a biopsy difficult. For sessile lesions, the biopsy is taken using a cervical biopsy forceps (eg, Kevorkian). Some raised or pedunculated lesions can be grasped with a forceps and biopsied using a fine scissor (eg, Metzenbaum). Hemostasis is usually obtained with application of Monsel solution or use of silver nitrate. If bleeding persists, a suture may be necessary.

DIAGNOSIS AND DIFFERENTIAL

Diagnosis — The diagnosis of VaIN is made by characteristic histologic findings on biopsy; specifically, VaIN is defined by the presence of squamous cell atypia without invasion.

In our practice, we review all VaIN pathology slides. As discussed above, VaIN 2 is considered to be an intermediate lesion (as classified by the Lower Anogenital Squamous Terminology [LAST] Standardization Project). During our review, we reclassify VaIN 2 into low-grade or high-grade lesions, which affects management considerably. (See 'Classification' above and 'Treatment' below.)

Differential diagnosis — The differential diagnosis includes vaginal cancer, which is distinguished from VaIN by the presence of invasion. (See "Vaginal cancer".)

Other benign etiologies, such as Gartner duct cysts, vaginal polyps, vaginal adenosis, or endometriosis, are in the differential for both VaIN and vaginal cancer. These are discussed elsewhere. (See "Vaginal cancer", section on 'Differential diagnosis'.)

TREATMENT — The treatment of VaIN depends on grade (algorithm 1).

Low-grade VaIN — We manage patients with low-grade VaIN (ie, VaIN 1 and VaIN 2 lesions that are reclassified as VaIN 1 on pathology review) with close surveillance rather than treatment (algorithm 1). These low-grade lesions are often the result of infection with nononcogenic subtypes of human papillomavirus (HPV) and will regress spontaneously [11]. In postmenopausal patients, these lesions can be associated with atrophic changes and may respond to topical estrogen [47]. This is discussed in more detail elsewhere. (See "Genitourinary syndrome of menopause (vulvovaginal atrophy): Treatment", section on 'Vaginal estrogen therapy'.)

High-grade VaIN — High-grade VaIN (ie, VaIN 3 and VaIN 2 lesions that are reclassified as VaIN 3 on pathology review) has a higher risk of progression to squamous cell carcinoma of the vagina and is therefore treated (algorithm 1) (see 'Posttreatment surveillance' below). A broad range of treatment options are available and include excision, ablation, topical therapy, and radiation therapy.

First-line options

How to choose — The goals of treatment for VaIN 3 are to prevent disease progression while minimizing potential treatment sequelae. Previous treatment failures, the presence of multifocal disease, the patient's general health and comorbidities, as well as a desire to preserve sexual function are factors to consider in selecting a therapeutic course.

Our first-line approach to treatment of VaIN 3 is as follows (algorithm 1):

Excision is required for those patients with VaIN in whom:

A diagnostic specimen is needed for further evaluation.

A lesion is worrisome for possible invasive disease (eg, raised, ulcerative, or with irregular borders), irrespective of results from colposcopy/biopsy.

Lesions that cannot be fully visualized or that involve the vaginal vault or lateral fornices.

For patients lacking any of the features listed above, our approach is as follows:

For patients with single lesions, we treat with excision, provided that complete removal with satisfactory cosmetic and functional results is expected.

By contrast, we suggest ablative therapy rather than excision for patients with the following:

-Multifocal disease.

-Lesions in which excision would disrupt normal anatomy significantly and impair functional results.

Occasionally, topical therapy is used as first-line treatment in patients with early lesions and multifocal disease or those who are poor surgical candidates. (See 'Subsequent-line options' below.)

Complications most commonly associated with both excision and ablation include pain, scarring, and sexual dysfunction. In terms of efficacy, a review of 21 available studies on therapeutic modalities found that cure rates for VaIN were similar for excision, laser ablation, and an ultrasonic aspirator and dissector (69.0 to 87.5 percent) [48].

Surgical therapy — Surgical excision is the mainstay of VaIN treatment (table 2). (See 'How to choose' above.)

This approach permits histologic diagnosis, which is a significant advantage over other treatments since invasive foci have been detected in up to 10 to 28 percent of specimens [22,44]. Surgical approaches include the following:

Wide local excision is the most commonly performed surgical procedure for VaIN 3. It is usually performed transvaginally, although at times an open or minimally invasive abdominal approach is necessary.

Partial vaginectomy is required when VaIN is buried in posthysterectomy suture recesses since these lesions are frequently inaccessible to other forms of treatment.

Total vaginectomy is performed rarely and reserved for extensive and persistent disease.

These surgical excision procedures are discussed in detail elsewhere. (See 'Subsequent-line options' below and "Vaginectomy".)

Complications of surgical therapy range from shortening or stenosis of the vagina due to wide local excisions to significant postoperative morbidity following abdominal procedures. The risk of complications is significantly increased in previously irradiated patients (for example, in patients with previously treated cervical cancer) [4]. Electrosurgical loop excision, laser vaginectomy, and ultrasonic surgical aspiration are modifications of the cold-knife approach that may promote rapid healing and reduce the frequency of complications [49-52].

Ablation — Ablative therapy is only performed if the lesion is fully visualized and invasive disease has been excluded by biopsy. It is typically preferred for younger patients and in those patients with multifocal disease to preserve normal anatomy. (See 'How to choose' above.)

Two commonly used ablative techniques include:

CO2 laser – The procedure is generally well tolerated, heals satisfactorily, and results in minimal sexual dysfunction (table 3) [53-61]. Pain and bleeding are the most frequent complications, requiring intervention in 20 percent of patients in one series [62]. Approximately one-third of patients will require more than one treatment with CO2 laser.

Ultrasonic surgical aspiration is associated with less postoperative pain and less vulvar scarring compared with CO2 laser [51].

Subsequent-line options — While surgery and ablation are the most common treatment methods for VaIN 3, a variety of alternate, less radical modalities have been used and studied. Topical therapy is a common next-line option for treatment of disease recurrence.

Topical application of therapeutic agents has the advantage of treating the entire vaginal mucosa, with good coverage of multifocal disease and disease in folds and recesses of the vagina. As with ablation, a prerequisite for topical treatment is that invasion has been excluded by thorough colposcopic examination and biopsy. Complications most commonly associated with topical therapies include pain, irritation, and superficial ulcerations.

Preferred: Imiquimod — Imiquimod may be a reasonably effective and well-tolerated topical therapy option for the treatment of VaIN 3. One reported regimen is 5% imiquimod cream applied to the vaginal lesions three times a week for eight weeks [63]. The most common adverse events are local burning and soreness, which are generally not severe enough for patients to discontinue treatment.

In a systematic review and meta-analysis of six studies including 94 patients with any grade VaIN, 5% imiquimod was associated with a complete response (CR) rate of 77 percent (95% CI 59.4-98.5) and an HPV clearance rate of 53 percent (95% CI 29.5-93.6) [64]. In a subsequent systematic review including 37 patients with VaIN 2 or 3, treatment with imiquimod resulted in a 76 percent CR rate; response rates were higher in patients with prior hysterectomy compared with patients without hysterectomy [65]. Larger studies with standardized treatment protocols and longer follow-up are needed to make safe conclusions regarding the effectiveness, recurrence rates, and durability (recurrence-free interval) of this treatment.

Alternative: Fluorouracil — Successful treatment of high-grade VaIN with fluorouracil (FU) has been reported in the literature with failure rates comparable to other techniques (table 4) [57,59,66-71]. Several dosing protocols have been suggested, ranging from twice daily application for 14 days to once weekly for 10 weeks. Complications of topical FU include vaginal irritation or burning and ulcerations [67,72]. External zinc oxide cream or petroleum jelly can be used as a barrier to help protect against ulceration in adjacent areas. Topical estrogen may also reduce patient discomfort.

In a meta-analysis including 14 observational studies including 358 patients with VaIN and treated with a first course of 5% FU, the overall CR rate was 82 percent; patients with high-grade VaIN had a CR rate of 78 percent [73].

A study of insertion of 2 g topical 5% FU cream at night once every two weeks for eight doses for the treatment of cervical intraepithelial neoplasia in young patients reported at least one side effect in 48 percent of patients (epithelial disruption, discharge, pain, burning); however, in no participant were these side effects so severe that they would interfere with usual activities [74]. Columnar metaplasia of the vaginal mucosa can occur after topical FU; the clinical significance of this finding is not known [75].

Last-line option

Radiation — Intracavitary radiation therapy is reserved for patients who have failed previous treatments, are poor surgical candidates, or who have extensive, multifocal disease. While radiation is an effective form of treatment, it is rarely used because simple resection of the cuff or ablative therapy is usually successful, and radiation is associated with higher rates of morbidity than other therapies. Vaginal complications caused by intracavitary radiation include atrophy, stenosis, and shortening. These anatomic distortions can interfere with sexual function and are an impediment to thorough colposcopic follow-up. Bowel and bladder changes and the induction of menopause can also occur. Poor wound healing of irradiated tissue is a concern for patients who subsequently require surgical intervention [20].

In one study of 14 patients who received high dose rate brachytherapy for VaIN 3, disease regressed (12 of 14; 85 percent), progressed to invasive cancer (1 of 12; 7 percent), or persisted (1 of 12; 7 percent) during a median follow-up of 46 months [76]. A study demonstrated the effectiveness of high dose rate brachytherapy with an 88 percent success rate for the treatment of VaIN in 34 patients with minimal acute side effects and 44 percent with mostly mild late toxicities [77]. In another series with median follow-up of 77 months, regression occurred in 17 of 22 patients who received medium dose rate brachytherapy for VaIN 3 [78]. Low dose rate brachytherapy has also been used [79].

POSTTREATMENT SURVEILLANCE — Management of VaIN requires long-term follow-up given a significant risk of progression to cancer for these patients irrespective of treatment modality used [80].

In a multicenter retrospective case study of 205 patients with biopsy-proven VaIN 2 or 3, progression to squamous cell carcinoma of the vagina was observed in nearly 6 percent of patients with a mean follow-up of 57 months (range 4 to 254 months) [80]. Patients at increased risk for progression were those with VaIN 3 (15 compared with 1.4 percent with VaIN 2) and those with prior hysterectomy for human papillomavirus (HPV)-related disease (17 versus 1.4 percent in nonhysterectomized patients). In a subsequent study including 337 patients with VaIN 3, rates of disease persistence, progression, and recurrence were 8.6, 7.4, and 4.2 percent, respectively, during the 14 month (median) follow-up period; older age and prior hysterectomy for cervical dysplasia were risk factors for progression [81]. Other studies have reported higher rates of disease recurrence, with one literature review reporting an 18 percent recurrence rate (range 0 to 50 percent) during follow-up periods of three months to 18 years (table 2) [4,13,18,22,39,40,50]. Recurrences of VaIN have also been described in vaginal tissue grafts performed to reconstruct the vagina after vaginectomy [82].

Posttreatment follow-up should include the following:

Clinical examination every six months for two years and annually thereafter.

Annual co-testing (cytology and HPV).

Given the high prevalence of HPV in VaIN, HPV testing, in addition to cytology, is preferred where available. In a retrospective study including 3229 patients with VaIN (over half of whom had VaIN 2 or 3), co-testing compared with cytology alone had higher sensitivity for VaIN only (97 versus 76 percent), concomitant VaIN (97 versus 79 percent), and VaIN after hysterectomy (98 versus 83 percent) [83].

Repeat colposcopy is performed for any HPV-positive test or any cytologic abnormality.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Vulvar cancer and vaginal cancer".)

SUMMARY AND RECOMMENDATIONS

Classification – Vaginal intraepithelial neoplasia (VaIN) is defined by the presence of squamous cell atypia without invasion. The disease is classified according to the depth of epithelial involvement: VaIN 1 involves the lower one-third of the epithelium and VaIN 3 involves more than two-thirds of the epithelium (picture 1). VaIN 2 is an intermediate lesion and is often reclassified to low-grade (VaIN 1) or high-grade (VaIN 3) on pathology review. (See 'Classification' above.)

Clinical presentation – VaIN is usually asymptomatic, although patients can present with postcoital spotting or vaginal discharge. It should be excluded in all patients with an abnormal Pap smear who are posthysterectomy or who do not have identifiable cervical lesions that could account for the abnormality. (See 'Clinical presentation' above.)

Diagnostic evaluation – Evaluation includes a thorough gynecologic examination with colposcopy and biopsies of any concerning lesions. Diagnosis is made by characteristic histologic findings on biopsy. In our practice, we review all VaIN pathology slides and reclassify VaIN 2 into VaIN 1 (low-grade) or VaIN 3 (high-grade) lesions. (See 'Diagnostic evaluation' above and 'Diagnosis and differential' above.)

Treatment – Treatment of VaIN depends on whether it is a low-grade or high-grade lesion (algorithm 1).

Low-grade VaIN – For patients with low-grade disease (VaIN 1 and VaIN 2 lesions that are reclassified as VaIN 1 on pathology review), we suggest surveillance rather than surgical treatment (Grade 2C). These lesions are often the result of infection with nononcogenic subtypes of human papillomavirus (HPV) or atrophic changes and will often regress spontaneously. (See 'Low-grade VaIN' above.)

High-grade VaIN – For patients with high-grade lesions (VaIN 3 and VaIN 2 lesions that are reclassified as VaIN 3 on pathology review), we suggest excision or ablation rather than surveillance (Grade 2C). The goals of treatment are to prevent disease progression while minimizing potential treatment sequelae. (See 'High-grade VaIN' above and 'How to choose' above.)

-For patients with a single lesion or lesions that are worrisome for possible invasive disease (eg, raised, ulcerative, or with irregular borders), we suggest surgical excision rather than ablation (Grade 2C). Excision is also favored for lesions that cannot be fully visualized (eg, lesions involving the vaginal vault or lateral fornices). (See 'Surgical therapy' above.)

-For patients with multifocal disease that is completely visualized, we suggest ablation rather than surgical excision (Grade 2C). However, invasive disease must first be excluded by biopsy prior to proceeding with ablation. (See 'Ablation' above.)

Recurrent VaIN – For patients with recurrent disease, we suggest topical therapy with imiquimod rather than a repeat excision or ablation (Grade 2C). Topical fluorouracil is a less commonly used alternative. These medications have the advantage of treating the entire vaginal mucosa, with good coverage of multifocal disease and disease in folds and recesses of the vagina. As with ablation, invasive disease must be excluded prior to treatment with topical therapies. (See 'Subsequent-line options' above.)

Last-line therapy – A last-line option for the treatment of VaIN 3 is radiation therapy. We suggest radiation for patients who have failed previous treatments, are poor surgical candidates, or who have extensive, multifocal disease. Radiation is associated with higher rates of morbidity than other therapies. (See 'Last-line option' above.)

Posttreatment surveillance – Management of VaIN requires long-term follow-up. In our practice, we perform HPV-based testing and clinical examination every six months for two years and annually thereafter to evaluate for persistent or progressive disease. (See 'Posttreatment surveillance' above.)

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Topic 3233 Version 26.0

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