Olesen TB, et al. - Researchers investigated the prevalence of human papillomavirus (HPV) DNA and p16 ^INK4a positivity in penile cancer and penile intraepithelial neoplasia worldwide. An association of a large proportion of penile cancers and penile intraepithelial neoplasias, with infection with HPV DNA (predominantly HPV16), was observed. This finding supports immunizing men and boys against HPV as this may be beneficial.

Methods

• This is a systematic review and meta-analysis.
• Until July 24, 2017, PubMed, Embase, and the Cochrane Library were searched for English-language articles published from Jan 1, 1986, onwards.
• These searched articles were required to report the prevalence of HPV DNA and p16 ^INK4a positivity, either alone or in combination, in at least five cases of penile cancer or penile intraepithelial neoplasia.
• Researchers included only studies that used PCR or hybrid capture for the detection of HPV DNA and immunohistochemical staining or methylation for the detection of p16 ^INK4a.
• Data extraction and subsequent crosschecking were carried out, and discussions regarding inconsistencies were performed to reach consensus.
• Stratifying by histological subtype and HPV DNA or p16 ^INK4a detection method, the pooled prevalence and 95% CI of HPV DNA and p16 ^INK4a positivity in penile cancer and penile intraepithelial neoplasia were estimated by using random-effects models.
• They estimated type-specific prevalence of HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, and HPV45 in penile cancer.

Results

• Of 1,836 non-duplicate records, 73 relevant papers (71 studies) were eligible.
• After pooling, 50·8% was recorded as the HPV DNA prevalence in penile cancer (52 studies; n=4199) (95% CI 44·8–56·7; I 2=92·6%, p _{heterogeneity}<0·0001).
• With regard to pooled HPV DNA prevalence, a high prevalence was reported in basaloid squamous cell carcinomas (84·0%, 95% CI 71·0–93·6; I 2=48·0%, p _{heterogeneity}=0·0197) and in warty-basaloid carcinoma (75·7%, 70·1–81·0; I 2=0%, p _{heterogeneity}=0·52).
• HPV16 was identified as the main oncogenic HPV type in penile cancer (68·3%, 95% CI 58·9–77·1), followed by HPV6 (8·1%, 4·0–13·7) and HPV18 (6·9%, 2·9–12·4).
• They estimated 79·8% pooled HPV DNA prevalence in penile intraepithelial neoplasia (19 studies; n=445) (95% CI 69·3–88·6; I²=83·2%, p _{heterogeneity}<0·0001).
• For p16 INK4a percent positivity in penile cancer (24 studies; n=2295), the pooled estimate was 41·6% (95% CI 36·2–47·0; I 2=80·6%, p _{heterogeneity}<0·0001), with a high pooled p16 INK4a percent positivity in HPV-related squamous cell carcinoma (85·8%, 95% CI 72·1–95·4; I 2=56·4%, p _{heterogeneity}=0·0011) vs non-HPV-related squamous cell carcinoma (17·1%, 7·9–29·1; I²=78·3%, p _{heterogeneity}<0·0001).
• Moreover, the p16 INK4a percent positivity was 79·6% (95% CI 65·7–90·7; I ²=89·9%, p _{heterogeneity}<0·0001) vs 18·5% (9·6–29·6; I ²=89·3%, p _{heterogeneity}<0·0001) in HPV-positive cases of penile cancer vs HPV-negative penile cancers, respectively.
• In penile intraepithelial neoplasia (six studies; n=167), the pooled p16 INK4a percent positivity was 49·5% (95% CI 18·6–80·7).