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HPV vaccination has been introduced in clinical practice in recent years and represents the most effective strategy of primary prevention of cervical carcinoma and of female genital preneoplastic conditions. One of the major issues of the subject is represented by vaccination coverage of the target population. Since its introduction, HPV vaccine efficacy has been progressively demonstrated also towards extragenital HPV-correlated conditions and in males too. Moreover, even subjects of older age groups or subjects who already had HPV infections have been demonstrated to received benefits from vaccination, due to improvements of their immunological response. Recently, vaccine efficacy has also been investigated in terms of adjuvant administration after treatments of preneoplastic or benign conditions of the female lower genital tract caused by HPVs; preliminary results indicate an interesting and promising field of application. On this basis, in this article an analysis of the state of the art has been performed, with specific regard to the Italian scenario and with the focus of future perspectives of implementation of the HPV vaccination policy. From the available evidences, the Italian HPV Study Group recommends the extension of systematic HPV vaccination to males too, to adult subjects and also after conservative treatment of genital HPV correlated conditions.

The aim of the present study is to re-update the clinical significance of vestibular papillomatosis. At the beginning of the eighties this condition has been related to HPV infection based on histological and/or molecular evidence of the virus presence and considered responsible of many cases of pruritus and/or vulvodynia. Based upon these findings a lot of clinicians have been treating this condition by laser ablation or by topical application of podophyllin or trichloroacetic acid. At present the majority of the authors believes that vestibular papillomatosis should be considered an anatomical variant of the vestibular mucosa not HPV related. Therefore HPV-DNA presence should be considered a causal rather than a causal agent. This evidence is important in defining the management of vestibular papillomatosis: the papillae are usually distinguishable from condylomata acuminata by clinical examination and biopsies or HPV testing are not necessary. According to the studies considering vestibular papillomatosis a non HPV related condition and on the bases of a series of 252 women examined, the Authors share the opinion that this clinical entity should be considered a normal vestibular findings. As a consequence no ablative treatment is usually required even if in presence of symptomatology or HPV molecular infection.

In 1986 the International Society For the Study of Vulvar Disease classified vulvar Paget's disease (VPD) as a non-squamous intraepithelial lesion of the vulva. The clinical multiform aspect of VPD, similar to other dermatological lesions, often delays the execution of a biopsy. Paget's cells could be instead easily identified at histological examination and with histochemical reactions. Underlying adenocarcinomas or stromal invasion are present in about 10% of intraepithelial VPD. Patients with VPD are at risk for a second synchronous or metachronous neoplasia: colo-rectal adenocarcinoma (more frequent in perianal localization of VPD), cervical adenocarcinoma, carcinoma of the transitional epithelium from the renal pelvis to urethra and mammary carcinoma. A wide spectrum of frequency of these associations is reported in the literature (0-45%). Therapy for intraepithelial VPD is wide and deep surgical resection comprising all the skin appendages. However VPD has a high frequency of recurrences (15-62%), often irrespective for radicality of surgical excision. When association with underlying invasive adenocarcinoma or stromal invasion is histologically confirmed, vulvar surgical approach must be integrated with inguino-femoral lymphadenectomy. The role of chemotherapy and radiotherapy in the multimodal approach to extensive or recurring VPD is still controversial. Recurrences or progression of intraepithelal VPD are reported more than 10 years from first surgical resection so that long term follow-up is mandatory.

Human papillomavirus subclinical lesions are well known on the cervix and are identified by colposcopy after acetic acid staining. The transfer of this technique from the cervix to the vulva has led to the identification of areas of white epithelial changes which have been defined by similarity as vulvar subclinical HPV (VSHPV) lesions. A critical revision of the different clinical VSHPV lesions classifications, the vulvar diagnostic role of acetic acid staining, the natural history of HPV infection and the histological-biomolecular diagnostic techniques has the authors to the conclusions that the majority of the "so called" VSHPV lesions should not be considered a real disease. The presence of HPV-DNA in these subclinical lesions should be considered causal and not causal. To avoid overtreatments in women with proven HPV-DNA positivity without macroscopic clinical lesions, the authors recommend to abandon the acetic acid staining on the vulva and invite to consider the VSHPV lesions a faked diagnosis and not a clinical entity.

The aim of this paper is to update the physicians (gynecologists, dermatologists and pathologists) on the evolution of vulvar disease terminologies. In doing that the authors illustrate briefly the fundamental steps which led to present classifications of the International Society for the Study of Vulvar Disease (ISSVD). The classification of "non neoplastic epithelial disorders" together with that of "intraepithelial alterations" are illustrated and compared with the terminologies previously employed. The last ISSVD definition of "superficially invasive carcinoma" of the vulva is also presented and discussed. The authors concluded that even if all these ISSVD classifications represent an important effort for reaching a common language for a better international exchange of different experiences, nevertheless an improvement of these terminologies is still requested.

The data on the natural history of vaginal intraepithelial neoplasia (VaIN) available in the literature are scarce and incomplete. As a matter of fact the majority of the Authors report series with a small number of cases, which are predominantly represented by VaIN III and usually already treated. Nevertheless from the review of the literature it seems that VaIN, particularly those of low grade (I-II), tend to show a high rate of spontaneous regression. The lesions are frequently multifocal, associated with papilloma virus (HPV) infection and arising in young women. On the contrary, the VaIN showing a more aggressive behaviour are usually represented by single lesions, arising in older women. Those patients are also frequently immunosuppressed, with a history of preceding genital neoplasia and a previous exposure to radiation and/or chemotherapy.

Thirty-two women with histologically confirmed cervical intraepithelial neoplasia (CIN) associated with human papillomavirus (HPV) infection were treated with intralesional beta-interferon. At 12 months from the end of the treatment, 60% of the patients showed complete regression, histologically assessed, of CIN. Considering separately the different CIN grades, the regression for CIN I was 71%, 64% for CIN II and 45% for CIN III. Side-effects were rather frequent (84%) but they did not require discontinuation of the treatment. On the basis of these data the Authors believe that intralesional beta-interferon, in selected cases, can play a role, as a conservative modality, among the different techniques of CIN therapy.