LaserCo₂ role in the treatment of vaginal intrepithelial neoplasia (VAIN) retrospective study involving 587 patients

Aim of the Study: To evaluate the presentation features of intraepithelial vaginal neoplasia, the clinical outcome in LaserCO₂ vaporization treated patients, the therapeutic results, the procedure-associated complications, and the risk factors for recurrence. Materials and Methods: This was a retrospective study of 587 consecutive patients diagnosed with vaginal intraepithelial neoplasia (VAIN) and treated by laserCO₂ vaporization at Spedali Civili of Brescia between January 1990 and June 2018. All the patients underwent cytological and colposcopic follow-up. Recurrences were evaluated in terms of clinical features and association with risk factors. Chi-Square was used to establish the correlation between the two groups. Results: Mean age was 40.9 years. Most lesions were localized at the vaginal superior third (94.4%), 55.3% were multifocal, and 49.5% were associated with synchronous intraepithelial cervical neoplasia (CIN). In 8% of cases, VAIN affected the vaginal vault in hysterectomized patients. In 84,4% among the 282 evaluable cases, a vaginal swab was positive for HPV. HR-HPV was more frequent in high-grade lesions. No intraoperative complications were registered and the treatment was well tolerated. Follow-up was available for 428 patients with a mean duration of 56 months. Complete regression of VAIN after treatment was 85.3% with a recurrence rate of 14.7%. HR-HPV has been identified as a significant risk factor for recurrence. Conclusions: LaserCO₂ vaporization is a safe, low impact, and effective technique for VAIN therapy with a high success rate. HR-HPV must be considered an independent risk factor for recurrence.

Vaginal intraepithelial neoplasia; Laser vaporization; Human papillomavirus; Colposcopy

[1] Cardosi R.J., Bomalaski J.J., Hoffman M.S.: “Diagnosis and management of vulvar and vaginal intraepithelial neoplasia”. Obstet. Gynecol. Clin. North Am., 2001, 28, 685

[2] Diakomanolis E., Stefanidids K., Rodolakis A., Haidopoulos D., Sindos M., Chatzipappas I., Michalas S.: “Vaginal intraepithelial neoplasia: report of 102 cases”. Eur. J. Gynaecol. Oncol., 2002, 23, 457.

[3] Rome R.M., England P.G.: “Management of vaginal intraepithelial neoplasia: a series of 132 cases with long term follow-up”. Int. J. Gynecol. Cancer, 2000, 10, 382.

[4] Sillman F.H., Fruchter R.G., Chen Y.S., Camilien L., Sedlis A., McTigue E.: “Vaginal intraepithelial neoplasia: risk factors for persistence, recurrence, and invasion and its management”. Am. J. Obstet. Gynecol., 1997, 176, 93.

[5] Sopracordevole F., Mancioli F., Clemente N., De Piero G., Buttignol M, Giorda G., Ciavattini A.: “Abnormal Pap Smear and Diagnosis of High-Grade Vaginal Intraepithelial Neoplasia: A retrospective Cohort Study”. Medicine, 2015, 94, e1827.

[6] Dodge J.A, Eltabbakh G.H., Mount S.L., Walker R.P., Morgan A.: “Clinical features and risk of recurrence among patients with vaginal intraepithelial neoplasia”. Gynecol. Oncol., 2001, 83, 363.

[7] Qing Cong, Yu Song, Qing Wang, Hongwei Zhang, Shujun Gao, Long Sui: “A Retrospective Study of Citology, High-Risk HPV, and Colposcopy Result of Vaginal Intraepithelial Neoplasia Patients”. Soares M.A. (ed). Cairo: Hindawi, BioMed Research International, 2018, Article ID 5894801.

[8] Jentschke M., Hoffmeister V., Soergel P., Hillemnns P.: “Clinical presentation, treatment and outcome of vaginal intraepithelial neoplasia”. Arch. Gynecol. Obstet., 2016, 293, 415.

[9] Kim M.K., Lee I.H., Lee K.H.: “Clinical Outcomes and risk of recurrence among patients with vaginal intraepithelial neoplasia: a comprehensive analysis of 576 cases”. J. Gynecol. Oncol., 2018, 29, e6.

[10] Sopracordevole F., Moriconi L., Di Giuseppe J., Alessandrini L., Del Piero E., Giorda G., et al.: “Laser Excisional Treatment for Vaginal Intraepithelial Neoplasia to Exclude Invasion: What Is the Risk of Complications?” J. Low. Genit. Tract Dis., 2017, 21, 311.

[11] Buck H.W., Guth K.J.: “Treatment of vaginal intrepithelial neoplasia (primarily low grade) with Imiquimod 5% cream”. J. Low Genit. Tract. Dis., 2003, 7, 290.

[12] Minucci D., Cinei A., Insacco E., Oselladore M.: “Epidemiological aspects of vaginal intraepithelial neoplasia (VAIN)”. Clin. Exp. Obstet. Gynecol., 1995, 22, 36.

[13] Murta E.F., Neves Junior M.A., Sempionato L.R., Costa M.C., Maluf P.J.: “Vaginal intraepithelial neoplasia: clinical therapeutic analysis of 33 cases”. Arc. Gynecol. Obstet., 2005, 272, 261.

[14] Piovano E., Macchi C., Attamante L., Fuso L., Maina G., Pasero L., Volante R., Zola P.: “CO2 laser vaporization for the treatment of vaginal intraepithelial neoplasia: effectiveness and predictive factors for recurrence”. Eur. J. Gynaecol. Oncol., 2015, 36, 383.

[15] Yang Y., Gao Y.L., Yu A.J., Zhang J.J.: “Clinical analysis of 13 cases with vaginal intraepithelial neoplasia”. Zhonghua Fu Chan Ke Za Zhi., 2010, 45, 197.

[16] Boonlikit S., Noinual N.: “Vaginal intraepithelial neoplasia: a retrospective analysis of clinical features and colpohistology”. J. Obstet. Gynaecol., 2010, 36, 94.

[17] Indraccolo U., Del Frate E., Cenci S., Ubertosi M., Donati Sarti R., Donati Sarti C., Baldoni A.: “Vaginal intraepithelial neoplasia and human papillomavirus infection: a report of 75 cases”. Minerva Ginecol., 2006, 58, 101. [In Italian]

[18] Diakomanolis E., Rodolakis A., Boulgaris Z., Blachos G., Michalas S.: “Treatment of vaginal intraepithelial neoplasia with laser ablation and upper vaginectomy”. Gynecol. Obstet. Invest., 2002, 54, 17.

[19] Vinokurova S., Wentzensen N., Einenkel J., Klaes R., Ziegert C., Melsheimer P., et al.: “Clonal hystory of papillomavirus-induced dysplasia in the female lower genital tract”. J. Natl. Cancer Inst., 2005, 97, 1816.

[20] Hampl M., Wentzensen N., Vinokurova S., Von Knebel-Doeberitz M., Poremba C., Bender H.G., Kueppers V.: “Comprehensive analysis of 130 multicentric intraepithelial female lower genital tract lesions by HPV typing and p16 expression profile”. J Cancer Res. Clin. Oncol., 2007, 133, 235.

[21] Yalcin O.T, Rutherford T.J., Chambers S.K., Chambers J.T., Schwartz P.E.: “Vaginal Intraepithelial neoplasia: treatment by carbon dioxe laser and risk factors for failure”. Eur. J. Obstet. Gynecol. Reprod. Biol., 2003, 106, 64.

[22] Gonzales Sanchez J.L., Flores Murrieta G., Chavez Brambila J., Deolarte Manzano J.M., Andrade Manzano A.F.: ‘Topical 5-Fluorouracil for treatment of vaginal intraepithelial neoplasms”. Ginecol. Obstet. Mex., 2002, 70, 244.

[23] Aho M., Vesterinen E., Meyer B., Purola E., Paavonen J.: “Natural History of vaginal intraepithelial neoplasia”. Cancer, 1991, 68, 195.

[24] Massad L.S.: “Outcomes after diagnosis of vaginal intraepithelial neoplasia”. J. Low. Genit. Tract. Dis., 2008, 12, 16.

[25] Hampl M., Sarajuuri H., Wentzensen N., Bender H.G., Keuppers V.: “Effect of human papillomavirus vaccines on vulvar, vaginal and anal intraepithelial lesions and vulvar cancer”. Obstet. Gynecol., 2006, 108, 1361.

[26] Srodon M., Stoler M.H., Baber G.B., Kurman R.J.: “The distribution of low and high-risk HPV types in vulvar and vaginal intraepithelial neoplasia (VIN and VAIN)”. Am. J. Surg. Pathol., 2006, 30, 1513.

[27] Sopracordevole F., Parin A., Scarabelli C., Guaschino S.: “Laser surgery in the conservative management of vaginal intraepithelial neoplasms”. Minerva Ginecol., 1998, 50, 507. [In Italian]

[28] Kalogirou D., Antoniou G., Karakitsos P., Botsis D., Papdimitriou A., Giannikos L.: “Vaginal intraepithelial neoplasia (VAIN) following hysterectomy in patient trated for carcinoma in situ of the cervix”. Eur. J. Gynaecol. Oncol., 1997, 18, 188.

[29] Wee W.W., Chia Y.N., Yam P.K.: “Diagnosis and treatment of vaginal intraepithelial neoplasia”. Int. J. Gynaecol. Obstet., 2012, 117, 15.

[30] Castle P.E., Rodriguez A.C., Porras C., Herrero R., Schiffman M., Gonzales P., et al.: “A comparison of cervical and vaginal human Papillomavirus”. Sex. Transm. Dis., 2007, 34, 849.

[31] Perrotta M., Marchitelli C.E., Velazco A.F., Tauscher P., Lopez G., Peremateu M.S.: “Use of CO2 laser vaporization for the treatment of high-grade vaginal intraepithelial neoplasia”. J. Low. Genit. Tract Dis., 2013, 17, 2.

[32] Bogani G., Ditto A., Martinelli F., Mosca L., Chiappa V., Rossetti D., et al.: “LASER treatment for women with high-grade vaginal intraepithelial neoplasia: A propensity-matched analysis on the efficacy of ablative versus excisional procedures”. Lasers Surg. Med., 2018, 50, 933.

[33] Kim H.S., Park N.H., Park I.A., Park J.H., Chung H.H., Kim J.W., et al.: “Risk factors for recurrence of vaginal intraepithelial neoplasia in the vaginal vault after laser vaporization”. Lasers Surg. Med., 2009, 41, 196.