Epidemiological studies have shown that HPV-related diseases are the most prevalent sexually transmitted infections. In this context, this report will present various clinical cases demonstrating the effectiveness of Acyclovir (ACV) or its prodrug Valaciclovir (VCV), both acyclic guanosine analogs commonly used for the treatment of HHV-1 and HHV-2, for the treatment of HPV-related diseases. The report shows the remission of five cases of penile condyloma and a case of remission in a woman affected by cervical and vaginal condylomas and a vulvar giant condyloma acuminate of Buschke and Lowenstein. The literature review shows that ACV is effective in treating skin warts when administered orally, topically, and intralesionally, suggesting its therapeutic potential in other diseases associated with HPV. ACV was also used successfully as an adjuvant therapy for juvenile and adult forms of laryngeal papillomatosis, also known as recurrent respiratory papillomatosis, prolonging the patient\'s symptom-free periods. Although the prevention of HPV infections is certainly achieved with the HPV vaccine, ACV and VCV have shown to be effective even against genotypes not included in the current vaccine and can be helpful for those problematic clinical cases involving unvaccinated individuals, immunocompromised patients, people who live with HIV, or non-responders to the vaccine. We and others concluded that randomized clinical trials are necessary to determine the efficacy of ACV and VCV for HPV-related diseases.

OBJECTIVE: In children, distinguishing anogenital warts (AGW) acquired innocently from those acquired by child sexual abuse (CSA) is challenging. High-quality studies examining this relationship are sparse. Here, we sought to evaluate the association between AGW and sexual abuse in children 12 years of age and younger with respect to wart location, age, and gender.
METHODS: A systematic review of Ovid MEDLINE, Embase, and Web of Science was performed for studies published on or before 2/16/2018. Studies were eligible for inclusion if they contained at least 10 patients 12 years old and younger and reported the number of patients who were sexually abused. The principal summary measures were the odds ratios (OR) of reported CSA with respect to subject age, wart location, and gender.
RESULTS: Three hundred twenty-seven studies were identified through record search. Twenty five were included in a summary synthesis (791 subjects); 10 were included in the final statistical analysis (199 subjects). In our overall review, 102 of 468 (21%) females and 36 of 204 (18%) males with AGW were abused or probably abused. Overlapping HPV types were found in abused and non-abused subjects. Perianal location and gender were not significant predictors of abuse. Both age and genital wart location (penis, vulva) did significantly predict CSA (α = .05). The odds ratio for sexual abuse of children aged 3-4 years was 7.45; 6.52 for ages 5-8 years; and 6.93 for ages 9-12 years compared to those 0-2 years of age. Genital location was associated with an OR of CSA of 5.93.
CONCLUSIONS: Our systematic review supports a significant association between AGW in a child greater than 2 years of age and odds of CSA. Genital wart location significantly predicts CSA as well. HPV typing is not a reliable method to ascertain CSA. Male family members and acquaintances were the most likely perpetrators of abuse.

According to our systematic literature review (PRISMA guidelines), only 37 vulvar squamous cell carcinomas (VSCCs) were diagnosed during pregnancy (age range: 17-41 years). The tumor size range was 0.3-15 cm. The treatment was performed after (14/37, 38%), before (10/37, 27%), or before-and-after delivery (11/37, 30%). We found that 21/37 (57%) cases were stage I, 2 II (5%), 11 III (30%), and 3 IVB (8%). HPV-related features (condylomas/warts; HPV infection; high-grade squamous intraepithelial lesion) were reported in 11/37 (30%) cases. We also found that 9/37 (24%) patients had inflammatory conditions (lichen sclerosus/planus, psoriasis, chronic dermatitis). The time-to-recurrence/progression (12/37, 32%) ranged from 0 to 36 (mean 9) months. Eight women died of disease (22%) 2.5-48 months after diagnosis, 2 (5%) were alive with disease, and 23 (62%) were disease-free at the end of follow-up. Pregnant patients must be followed-up. Even if they are small, newly arising vulvar lesions should be biopsied, especially in women with risk factors (HPV, dermatosis, etc.). The treatment of VSCCs diagnosed in late third trimester might be delayed until postpartum. Elective cesarean section may prevent vulvar wound dehiscence. In the few reported cases, pregnancy/fetal outcomes seemed to not be affected by invasive treatments during pregnancy. However, clinicians must be careful; larger cohorts should define the best treatment. Definite guidelines are lacking, so a multidisciplinary approach and discussion with patients are mandatory.

BACKGROUND: Several therapeutic options are available to manage anogenital warts (AGWs). However, no hierarchy of treatments is provided in the latest European and American recommendations. This study aimed to determine the efficacy and safety of local treatments for the management of AGWs.
METHODS: A search was conducted through 12 databases from inception to August 2018. All randomized controlled trials (RCTs) in which at least one parallel treatment group composed of immunocompetent adults with AGWs received at least one provider-administered or patient-administered treatment were included. Risk of bias assessment and meta-analyses of aggregated study data were performed on the basis of the Cochrane Handbook, and quality of evidence evaluation followed the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Primary endpoints were complete clearance and recurrence at 3 months.
RESULTS: Seventy RCTs (9931 patients) were included. All but four RCTs had a high risk of bias. CO2 laser was slightly more efficacious than cryotherapy [risk ratio (RR) 2.05; 95% confidence interval (CI) 1.61-2.62], with fewer recurrences at 3 months (RR 0.28; 95% CI 0.09-0.89). Electrosurgery was slightly more efficacious than cryotherapy. No differences in efficacy or side effects were found between cryotherapy and imiquimod or trichloroacetic acid. Podophyllotoxin gel was slightly more efficacious than podophyllotoxin cream. 5-Fluorouracil (5-FU) was slightly more efficacious and caused less erosion than CO2 laser (RR 1.37; 95% CI 1.11-1.70).
CONCLUSIONS: The vast majority of included RCTs had a low level of evidence, thereby preventing the establishment of a hierarchy of treatments. Nevertheless, our results provide an overview of the main AGW treatments available for general practitioners and specialists. While provider-administered treatments are superior, patient-administered treatments (e.g., imiquimod, podophyllotoxin) are useful solutions for compliant patients.
BACKGROUND: PROSPERO-CRD42015025827.

BACKGROUND: Cryotherapy is one of the most commonly used therapeutic modalities to treat anogenital warts (AGWs), but this treatment was not clearly established in the recent international recommendations.
OBJECTIVE: To compare the efficacy and safety of cryotherapy versus other AGW treatments.
METHODS: Through a systematic search of 12 electronic databases, we identified 11 randomized controlled trials, screened from database inception through October 2016, that met the inclusion criteria (including immunocompetent adults with AGWs receiving cryotherapy in 1 of the comparison groups). Primary endpoint was complete clearance of AGW. Risk-for-bias assessment was based on Cochrane Handbook recommendations. Meta-analyses used Review Manager v5.3 software.
RESULTS: Cryotherapy efficacy did not appear to differ from that of trichloroacetic acid, podophyllin, or imiquimod. Electrosurgery was weakly associated with better AGW clearance than cryotherapy (risk ratio [RR] 0.80, 95% confidence interval [CI] 0.65-0.99). Cryotherapy was associated with more immediate low-level adverse events (erythema, stinging, or irritation; RR 3.02, 95% CI 1.38-6.61) and immediate pain requiring oral analgesics (RR 2.11, 95% CI 1.07-4.17) but fewer erosions (RR 0.57, 95% CI 0.36-0.90).
CONCLUSIONS: All but 1 randomized-controlled trial had a high risk for bias.
CONCLUSIONS: With low-level quality of the evidence, cryotherapy is an acceptable first-line therapy to treat AGWs.

Anogenital warts (AGW, condylomata acuminata) and intraepithelial neoplasia (IEN) do not only impact health and social well-being, they are also associated with considerable costs for the healthcare systems. Immunocompromised and HIV-positive patients carry the highest epidemiological burden of human papillomavirus (HPV) infection and comprise a population specifically susceptible to treatment failures and recurrences. This systematic review aimed at identifying and appraising the available evidence from controlled studies of interventions for the treatment of AGW and IEN in immunocompromised patients.
We conducted a comprehensive literature search. The Cochrane Collaboration\'s tool was used to assess risk of bias in included studies. Our confidence in the (pooled) effect-estimates was evaluated according to the Grading of Recommendations Assessment, Development and Evaluation approach. All evaluations were based on data independently extracted by two review authors.
Nine randomised controlled trials and two controlled studies were eligible, investigating external AGW, intra-anal and/or vaginal warts, and intra-anal and/or perianal IEN. The identified studies assessed imiquimod, cidofovir, fluorouracil, electrocautery, systemic interferon-α and interferon-β, and the combination of intralesional interferon-α and podophyllin. Four studies combined an ablational intervention with either imiquimod, cidofovir, intralesional or systemic interferon-α. One study investigated an experimental therapeutic vaccination (HPV 16 E7) at different concentrations.
The quality of the evidence ranged from \'very low\' to \'moderate\' and was limited by the often small samples. Evidence was available for the efficacy of electrocautery for intra-anal IEN, and imiquimod cream for external AGW. Some further interventions should be subjected to investigations in larger samples. No data on some interventions established for the treatment of AGW in immunocompetent patients such as podophyllotoxin, sinecatechins, laser ablation or trichloroacetate were available. Future trials should address these gaps and include relevant patient-reported outcomes such as health-related quality of life.

Anogenital warts (AGWs, condylomata acuminata) are among the most common STIs and may severely impact quality of life (QoL). Available treatment options are characterised by a high proportion of non-responders and recurrences.
To systematically review and meta-analyse the available evidence from randomised controlled trials (RCTs) on topical treatments for AGWs considering short-term and long-term efficacy, effects on QoL and adverse events (AE).
A comprehensive literature search was performed in Cochrane Central Register of Controlled Trials, Embase and MEDLINE. Included studies were evaluated with the Cochrane Collaboration\'s risk of bias tool. The confidence in the pooled effect estimates was evaluated according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and categorised as \'very low\', \'low\', \'moderate\' or \'high\'.
Eighteen RCTs met the inclusion criteria. Regarding complete clearance (CC), imiquimod 3.75% and 5% cream, podophyllotoxin 0.5% solution and gel and polyphenon E 10% and 15% ointment were superior to placebo. Although more local AE and pain occurred in the actively treated groups, differences regarding dropouts due to AE were not statistically significant. For podophyllotoxin 0.15% cream, no placebo-controlled trials were available; however, in an active-controlled trial, it was inferior to podophyllotoxin 0.5% solution with respect to CC. No significant differences were detected between imiquimod 5% cream and podophyllotoxin 0.5% solution and between polyphenon E 10% and 15% ointment. No data on the influence on health-related QoL were available.
Our confidence in the pooled estimates (GRADE quality of the evidence) ranged from very low to high. Apart from the given results, other aspects such as availability, costs or patient preference have to be considered when making a treatment choice. Due to the limited number of direct comparisons, conclusions on the relative efficacy of the different treatment options are restricted.

BACKGROUND: The human papilloma virus (HPV) is a carcinogen known for its strong association with cervical cancers and cervical lesions. It is also known to be associated with a variety of squamous cell carcinomas in other areas, such as the penis, vulva, anus and head and neck. However, the association with urothelial carcinoma remains controversial. Here, we report a case of urothelial carcinoma with squamous differentiation associated with HPV-6/HPV-11.
METHODS: This is a case of a 70 year old man who presented with nocturia and pressure during urination. During the TURP procedure for what was clinically thought to be benign prostate hyperplasia with pathologic diagnosis as prostate carcinoma, a 2 cm papillary mass was found in the distal penile urethra. The papillary mass was found to be a high grade urothelial carcinoma positive for GATA 3 expression, with focal areas of squamous differentiation. The areas with squamous differentiation demonstrated koilocytic differentiation, which were positive for strong p16 expression. The tumor was found to harbor low risk HPV 6/11 by in situ hybridization.
CONCLUSIONS: This study case demonstrates HPV infection with a low risk subtype (HPV 6/11) associated with an urothelial carcinoma with squamous differentiation and condylomatous features.

OBJECTIVE: Worldwide, transgender women are an at-risk population for contracting sexually transmitted infections. Little information exists on symptoms and characteristics of neovaginal human papillomavirus (HPV) infections and associated diseases. We describe a case series of transgender women with symptomatic HPV-related neovaginal lesions and a review of current literature.
METHODS: Transgender women with symptomatic HPV-related neovaginal lesions were identified from a departmental database comprising clinical and outpatient data on transgender women who underwent vaginoplasty between 1990 and 2015. HPV status was determined on excision and biopsy specimens by HPV DNA testing using GP5+6+-PCR and p16INK4A immunohistochemistry. Current literature was reviewed using the MEDLINE and EMBASE databases.
RESULTS: This case series includes four transgender women with symptomatic, HPV-related neovaginal lesions. Two women presented with neovaginal and neovulvar pain and condylomata/leukoplakia, which were excised. These lesions showed moderate-to-severe dysplasia at histopathological examination, and were positive for high-risk HPV (hrHPV) and p16INK4A. Recurrence occurred in one patient and was treated with laser evaporation. Two women presented with neovaginal coital pain, neovaginal bleeding and condylomata. Neovulvar lesions were treated with podophyllotoxin. Neovaginal lesions were excised or evaporated. These lesions were low-risk HPV (lrHPV) positive. The literature search shows treatment options varying from conservative, topical podophyllotoxin to excision or laser evaporation under general anaesthesia.
CONCLUSIONS: Neovaginal HPV infection can lead to benign condylomata (lrHPV) and various grades of dysplasia (hrHPV). We advise physicians to consider HPV infection and associated lesions in transgender women with otherwise unexplainable neovaginal pain or bleeding after vaginoplasty.

Verrucous carcinoma of the vulva is a rare lesion (1). Affecting essentially postmenopausal women, this lesion is a distinct and particular entity in vulval carcinoma classification and its scalability is uncertain and unpredictable. Here, we present a case concerning a 48-year-old patient, without follow-up after a condyloma acuminate of the vulva (large left lip). The origin of this case will be discussed in this article. The treatment decided was only surgical. A review of literature shows the rarity of this lesion of the female genital tract.