High-grade and low-grade HPV-induced urethral lesions treated by CO2 laser under colposcopy.

OBJECTIVES: This study is reporting the CO2 laser treatment efficiency on urethral lesions caused by human papillomavirus (HPV) and the correlation between the type of lesion high-grade and low-grade on the histology and the HPV genotype(s). METHODS: Sixty-nine patients (59 men and 10 women) with urethral lesions were screened for HPV genotype(s) by in situ hybridisation and PCR. HPV lesions were biopsied and p16INK4a expression was tested to confirm urethral high-grade squamous intraepithelial lesions (U HSIL) on the histology prior to CO2 laser treatment under colposcopy. The patients were followed up for 12 months. RESULTS: We observed urethral low-grade squamous intraepithelial lesions (U LSIL) in 54/69 cases (78.3%) and U HSIL in 7/69 cases (10%) confirmed by p16INK4a staining. Then we looked at the HPV genotype present in each lesion. We observed the following: 31/69 (45%) patients have a unique HPV genotype, with 12/31 (38.7%) of high risk; 21/54 (38.8%) of U LSIL and 1/7 (14%) of U HSIL have HPV low-risk and high-risk coinfections. Efficient treatment with CO2 laser under colposcopy was done using a meatal spreader to help visualisation of 20 mm in the distal urethra. We cured 64/69 (92.7%) patients at 3 months with 4/69 (5.7%) meatotomy and persistent 1/67 (1.4%) urethral stricture at 12 months. CONCLUSIONS: HSIL was present in the urethra without being able to define specific clinical criteria. Treatment with a CO2 laser under colposcopy with a meatus spreader is a simple surgical procedure with high efficiency and few complications that could prevent the risk of HPV-induced carcinoma.

Potential impact of the human papillomavirus vaccine on the incidence proportion of genital warts in French women (EFFICAE study): a multicentric prospective observational study.

UNLABELLED: Background The objective was to evaluate the effect of a HPV vaccination program on the incidence proportion of a proxy, genital warts (GW), in women in France. METHODS: The number of primary GW cases was prospectively recorded over two 4-month periods before (T0: Dec 2008 to March 2009) and after (T1: Dec 2011 to March 2012) a HPV vaccination program. A total of 160 gynaecologists participated in T0 and 189 in T1. Primary genital herpes (HSV) infection was used as a control. RESULTS: During T0, 39190 15- to 26 year-old women were seen, of whom 176 were diagnosed with GW (incidence proportion: 0.45%) and 155 with primary HSV infection (incidence proportion: 0.39%). During T1, 45628 females were seen [229 with GW (incidence proportion: 0.50%) and 202 with HSV (incidence proportion: 0.44%)]. In the 15-20 years age category, the incidence proportion of primary GW decreased from 0.41% to 0.30% (P=0.128) between T0 and T1, and the proportion of women newly diagnosed with primary genital herpes diseases slightly increased from 0.34% to 0.38% (P=0.620). In the 15-18 years age group, this decrease became significant (0.34% to 0.18%; P=0.048). CONCLUSIONS: A trend for a non-significant decreased incidence proportion of GW was observed in young women below 20 years who are more frequently vaccinated. This may be the result of HPV vaccination and suggests that a substantial increase in vaccine coverage could lead to a more pronounced decreased incidence proportion of GW in the future.

Human papillomavirus genotype distribution in anal cancer in France: the EDiTH V study.

Anal cancer is a rare cancer but its incidence is increasing. Human papillomavirus (HPV) infection seems to be associated with the occurrence of most cases. The genotype-specific prevalence of HPV in anal cancer was estimated to assess the potential benefit of HPV vaccination in France. Anal cancer histological specimens were retrospectively recruited in 2008 from 16 French centres and centrally tested for HPV genotyping using the INNO-LiPA assay allowing the detection of 28 genotypes. Results were analyzed according to age, gender, HIV status when available and histological diagnosis. A total of 366 anal cancer cases were analyzed among which 62% were females. Mean age at diagnosis was 54.8 years in males and 66.4 years in females (p < 0.001). HPV was found in 96.7% of cases, 72% being infected by a single HPV type. Presence of at least one high-risk genotype was observed in 91% of cases (96% in females and 83% in males; p < 0.001). HPV16 was by far the most prevalent genotype (75%), followed by HPV18, HPV52, HPV33, and HPV51 (4-6%). HPV16/18 alone or in association were found in 78% of all cases. HIV-positive cases had a higher proportion of multiple HPV infection than HIV-negative cases and a slightly different HPV type distribution with an under-representation of HPV16 and an over-representation of other types. Our results indicate that anal cancer rarely occurs in the absence of HPV and emphasize the predominant role of HPV16. The potential benefit of HPV vaccine on the occurrence of anal cancer should be further evaluated.

Study of persistence and recurrence rates in 106 patients with condyloma and intraepithelial neoplasia after CO2 laser treatment.

Our aim was to evaluate remission and relapse rates and the number of laser sessions necessary for treatment. Among the relapses observed, we sought to differentiate between the persistence and recurrence of an HPV-induced lesion. This retrospective study was performed in patients, immunocompetent or not, treated with CO2 laser for condylomatous or neoplastic anogenital lesions by the same operator over a period of 12 months. 106 treated patients were followed for 6 months. Three groups of patients were analysed: HIV(+) patients, patients with therapeutic immunosuppression (ImST) and immunocompetent patients (ImC). Twenty-seven (25.5%) patients presented with high-grade intraepithelial neoplasms (IEN III). IEN III lesions were more common in the HIV(+) group than in immunocompetent patients (47.4% versus 20.2%, p = 0.015). The development of HPV-induced lesions at several sites on the body was also more common in HIV(+) patients. Post-laser controls at one month demonstrated a clinical absence of HPV-induced lesions in 81.2% of cases, recurrence in 12.6% of cases and persistence in 6.6% of cases. Remission rates at one month did not differ significantly between the three groups. 93% of patients in remission at one month were still in remission at three months. IEN III neoplasms in remission at one month remained so at six months. ImC and ImST patients presented more frequently with recurrence than persistence, when compared with HIV(+) patients. At six months, 83% of patients were in remission after 1.4 laser treatments. The excision of HPV-induced anogenital lesions using CO2 laser remains an efficient treatment, even if it needs to be repeated if lesions recur or persist. CO2 laser treatment under colposcopic guidance can achieve remission in both immunocompromised and non-compromised patients with longstanding lesions.

[Penile intraepithelial neoplasia]. / Les néoplasies intra-epithéliales du pénis.

The increasing incidence of anogenital carcinoma in situ in young adults over the last twenty years is correlated with certain sexually transmissible diseases. This increased incidence of genital lesions requires a review of the clinicopathological classification of penile intraepithelial neoplasia (PIN) to help the clinician differentiate the aetiology in order to propose the least mutilating treatment. Bowen-like or human papillomavirus (HPV)-induced PIN in young men present different clinical features and a different natural history from those of high-grade PIN of elderly men. This distinction between the clinical features and the period of development of the lesions according to their histology, differentiated, undifferentiated or borderline, allows evaluation of the risk of progression of the intraepithelial neoplasia. Lesions corresponding to oncogenic HPV infection, often involving all of the anogenital region, require clinical surveillance to avoid possible carcinomatous transformation. Most importantly, the detection and treatment of these lesions participate in the prevention of cervical cancer.

Cytologic detection of human papillomavirus DNA in normal male urethral samples.

OBJECTIVES: To quantify the existence of human papillomavirus (HPV) infection without detectable lesions in the male urethra, and to verify the sensitivity and specificity of ureteral cytology. We compared the results of clinical and colposcopic examinations, ureteral cytology, and HPV DNA testing by polymerase chain reaction amplification in the male partners of women with genital HPV disease. METHODS: A total of 110 cytobrush samples of urethral cells from male sexual partners of women with genital HPV-associated lesions were analyzed by cytology and for virologic detection of HPV 6/11, 42, 16/18 by polymerase chain reaction followed by Southern blot hybridization. The results were correlated with the presence or absence of genital HPV-associated lesions. RESULTS: HPV DNA was detected in 1 sample (3%) from men without visible lesions, in 5 samples (15%) from men with penile lesions but without urethral lesions, and in 16 men with urethral lesions (78%). Cytology showed cellular changes suggesting HPV infection in 81% of men with urethral lesions, but also in 15% of men without lesions. CONCLUSIONS: Our results show that HPV-DNA positivity in the absence of clinically or colposcopically detected lesions is a rare event. Although sensitive enough, cytology is not specific, and its use as a screening tool may lead to a high number of false-positive results.

Frequency of herpes simplex virus, cytomegalovirus and human papillomavirus DNA in semen.

Herpes simplex virus (HSV-2) and cytomegalovirus (CMV) infections produce brain damage in the newborn, and human papillomavirus (HPV) plays a role in cervical carcinogenesis. To assess the frequency of herpes virus and HPV in semen and its role in transmission, semen from 111 male partners of women with histologically-detected genital HPV infection was analysed for HSV, CMV and HPV infection. We used cell culture to detect HSV and CMV, and polymerase chain reaction (PCR) for HPV. Virological findings in the sperm were correlated to the presence or absence of HPV-associated genital lesions and to the viral type. Viral cultures yielded HSV-2 DNA in 9% and CMV DNA in 6.3% of cases. No correlation was established with a history of clinically apparent infection for HSV. HPV-DNA was detected in 23.4% of semen by PCR techniques: in 48% of subjects with urethral lesions, in 22% of patients with penile lesions, in 2% of patients without HPV-associated lesions. HPV-DNA type 16 was detected in 3.6% of cases. Patients with a positive HPV semen sample and penile or urethral lesions had the same HPV type detected in the two specimens. The study shows a high detection of clinically inapparent HSV and CMV, but does not confirm high HPV prevalence in semen from men without detectable lesions. Our study also suggests that the mechanism for semen contamination by HPV is the exfoliation of infected cells from urethral lesions during semen ejaculation, and probably, by abrasion from penile lesions. This could result in the contamination of semen used in assisted reproductive technology.

[Buschke-Lowenstein penile tumor]. / Tumeur pénienne de Buschke-Löwenstein.

The Buschke-Löwenstein genital tumour is a poorly defined, uncommon tumour. The distinction between benign lesions, potentially malignant lesions and carcinomatous lesions is difficult. The authors report a case of Human Papillomavirus (HPV) 11-associated Buschke-Löwenstein tumour with an area of micro-invasive carcinoma on histological examination of the surgical resection specimen. A 34-year-old patient was operated for recurrent condylomatous lesions of the penis with scrotal extension. Histological examination of the complete operative specimen confirmed the presence of Buschke-Löwenstein tumour as well as an area of dermal micro-invasion on one section. Molecular hybridization revealed the presence of HPV 11 DNA and immunohistochemistry showed basal cells weakly expressing mutant p53. The classification of Buschke-Löwenstein tumours is controversial. Some authors consider these tumours to be benign tumours or giant condylomata (non-metastatic, associated with HPV 6-11), while others consider these tumours to be borderline malignant (local extension and risk of progression to invasive carcinoma). The role of HPV as cofactor involved in carcinomatous transformation also remains controversial. The authors emphasize the need for surgical resection of this type of tumour with histological examination of the entire operative specimen looking for areas of micro-invasion. In the presence of micro-invasion with healthy resection margins and staging by clinical examination and complementary investigations, treatment essentially consists of regular surveillance.