Low-grade squamous intraepithelial lesions (LSIL) associated with certain human papillomavirus (HPV) genotypes may preferentially progress to cervical cancer. HPV genotyping may thus have the potential to improve the effectiveness of screening programs and to reduce overtreatment. LSIL cases (n = 8,308) from 55 published studies were included in a meta-analysis. HPV genotype distribution was assessed by geographic region and in comparison with published data on cervical squamous cell carcinoma (SCC). HPV detection in LSIL was 80% in North America but less than 70% in other regions, most likely reflecting regional differences in LSIL diagnosis. Among 5,910 HPVpositive LSILs, HPV16 was the most common genotype (26.3%) followed by HPV31 (11.5%), HPV51 (10.6%), and HPV53 (10.2%). HPV-positive LSILs from Africa were 2-fold less likely to be infected with HPV16 than those in Europe, and HPV-positive LSILs from North America were more likely to be infected with HPV18 than those from Europe or South/Central America. Interpretation for rarer genotypes was hampered by variation in HPV testing methodology. SCC/LSIL prevalence ratios indicated that HPV16 was 2-fold and HPV18 was 1.5-fold more common in SCC than in HPV-positive LSIL, thus appearing more likely to progress than other high-risk genotypes (SCC/LSIL prevalence ratios between 0.05 and 0.85). HPV53 and HPV66 showed SCC/LSIL ratios of 0.02 and 0.01, respectively. HPV genotype distribution in LSIL differs from that in cervical cancer, highlighting the importance of HPV genotype in the risk of progression from LSIL to malignancy. Some regional differences in the relative importance of HPV genotypes in LSIL were noted.

Detection of persistent cervical carcinogenic human papillomavirus (HPV) DNA is used as a marker for cervical cancer risk in clinical trials. The authors performed a systematic review and meta-analysis of the association between persistent HPV DNA and high-grade cervical intraepithelial neoplasia (CIN2-3), high-grade squamous intraepithelial lesions (HSIL), and invasive cervical cancer (together designated CIN2-3/HSIL+) to evaluate the robustness of HPV persistence for clinical use. MEDLINE and Current Contents were searched through January 30, 2006. Relative risks (RRs) were stratified by HPV comparison group. Of 2,035 abstracts, 41 studies were eligible for inclusion in the meta-analysis. Over 22,500 women were included in calculation of RRs for persistent HPV DNA detection and cervical neoplasia. RRs ranged from 1.3 (95% confidence interval: 1.1, 1.5) to 813.0 (95% confidence interval: 168.2, 3,229.2) for CIN2-3/HSIL+ versus 12 months), wider testing intervals, CIN2-3/HSIL+, and use of an HPV-negative reference group were consistently associated with higher RRs. Thus, HPV persistence was consistently and strongly associated with CIN2-3/HSIL+, despite wide variation in definitions and study methods. The magnitude of association varied by duration of persistence and testing interval. Precise definition and standardization of HPV testing, sampling procedure, and test interval are needed for reliable clinical testing. These findings validate HPV persistence as a clinical marker and endpoint.

A systematic review was conducted of HPV type distribution in anal cancer and anal high-grade and low-grade squamous intraepithelial lesions (HSIL and LSIL). A Medline search of studies using PCR or hybrid capture for HPV DNA detection was completed. A total of 1,824 cases were included: 992 invasive anal cancers, 472 HSIL cases and 360 LSIL cases. Crude HPV prevalence in anal cancer, HSIL, and LSIL was 71, 91 and 88%, respectively. HPV16/18 prevalence was 72% in invasive anal cancer, 69% in HSIL and 27% in LSIL. The HPV 16 and/or 18 prevalence in invasive anal cancer cases was similar to that reported in invasive cervical cancer. If ongoing clinical trials show efficacy in preventing anal HPV infection and associated anal lesions, prophylactic HPV vaccines may play an important role for the primary prevention of these cancers in both genders. ' 2008 Wiley-Liss, Inc.Key words: human papillomavirus; anal cancer; anal neoplasia; review; epidemiology Anal cancer is a slowly progressing disease that begins as a superficial mass and may spread locally, involve regional lymph nodes or metastasize to distant organs. 1 Globally, annual incidence rates of invasive anal cancer range from 0.1 to 2.8 cases per 100,000 among men and 0.0 to 2.2 per 100,000 among women (specific rates as defined by C21 ICD-9 code). 2 Although the incidence of anal cancer in the United States (0.9 cases per 100,000 population) is relatively low compared with cervical cancer (8 cases per 100,000 women), anal cancer rates among men who have sex with men (MSM) are notably higher. Among HIV-seronegative MSM, the estimated incidence of anal cancer is 35 cases per 100,000, and this rate doubles to 70 cases per 100,000 among HIV-seropositive MSM. 3 With the introduction of highly active antiretroviral therapy, anal cancer rates have continued to increase, possibly reflecting the longer life-expectancy in a generally unscreened HIV-seropositive population. 4 It is known that invasive cervical cancer among women is preceded by cervical intraepithelial neoplasia (CIN) 2-3. Similarly, invasive anal cancer has well-documented precursors, known as anal intraepithelial neoplasia (AIN) 2-3 (histology) or high-grade squamous intraepithelial lesions (HSIL) (cytology). 5 AIN 1 and cytological low-grade squamous intraepithelial lesions (LSIL) are not considered direct precursors of invasive anal cancer, but may precede the later development of AIN2/3 or HSIL.Invasive anal cancer, like invasive cervical cancer, has been causally linked to high-risk human papillomavirus (HPV) infection. [6][7][8][9] Carcinogenic types of human papillomavirus (HPV) infection have been detected in more than 99% percent of invasive cervical cancer cases using sensitive polymerase chain reaction (PCR) assays. 10,11 To date, no literature review has been conducted to quantify overall and type-specific prevalence of HPV among invasive anal cancer and preinvasive anal lesions. Data on the proportion of anal cancer cases attributable to specific types of HPV infection are important to pre...

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HPV DNA was detected in half of SCC, with HPV16 being the most common type. If proven efficacious in men, prophylactic vaccines targeting carcinogenic types HPV16 and 18 could potentially reduce approximately one-third of incident SCC.