Trends in incidence and survival from anal cancer and incidence of high-grade anal intraepithelial neoplasia in Denmark.

OBJECTIVE: The aim of the current study was to assess temporal trends in incidence of anal squamous cell carcinomas (SCC) and high-grade anal intraepithelial lesions (AIN2/3), and estimate survival from anal cancer and factors related to 5-year mortality in Denmark. METHODS: We analyzed anal SCC and AIN2/3 cases in the period of 1998-2018 from the Danish Cancer Register and the Danish Registry of Pathology, respectively. Overall, period, gender, and histology specific age-standardized incidence rates, average annual percentage change (AAPC), and 5-year relative survival were estimated. Cox proportional hazards models were applied to evaluate the effect on 5-year mortality of period, age, gender, and stage of disease. RESULTS: Altogether 2580 anal cancers and 871 AIN2/3 were identified. The AIN2/3 incidence increased for women 1998-2007 (AAPC: 3.5% (95% CI -0.7, 8.0)) and then tended to decrease during 2008-2018(AAPC: -5.2% (95% CI -9.6, -0.6)). A similar pattern was observed for men, although at a lower incidence with the decrease starting later (2008-2012) and the trend not reaching statistical significance. The anal SCC incidence increased over the whole study period for both women and men (women AAPC: 4.0% (95% CI 3.2%, 4.9%) and men AAPC: 3.6% (95% CI 2.3%, 4.9%)). The relative survival improved over time (from 61% to 72%). Being older and male was associated with a higher risk of dying within 5 years. CONCLUSIONS: There is a need to focus attention on anal cancer and its precursor lesions, as the cancer incidence continues to increase. Actions could include screening and gender-neutral HPV vaccination.

Incidence of penile intraepithelial neoplasia and incidence and survival of penile cancer in Denmark, 1997 to 2018.

PURPOSE: Squamous cell carcinoma (SCC) of the penis is rare. Some studies have suggested that the incidence is increasing but the available literature is equivocal. We examined the incidence of high-grade penile intraepithelial neoplasia (PeIN), the incidence and 5-year relative survival as well as mortality of penile SCC in Denmark over the latest 20 years. METHODS: New cases of high-grade PeIN and penile cancer were identified from high-quality nationwide registries. Age-standardized (World) incidence rates per 100,000 person-years and average annual percentage change (AAPC) were estimated. For penile SCC, 5-year relative survival was calculated, and Cox regression was used to examine the effect of selected characteristics on mortality. RESULTS: Altogether, 1,070 new cases of high-grade PeIN were diagnosed (1997-2018) and the incidence increased from 0.87 to 1.84 per 100,000 person-years from 1997-1998 to 2017-2018 (AAPC = 4.73; 95% CI: 3.54-5.94). We identified 1,216 penile cancer cases (1997-2018) (95.7% SCC). The incidence of penile SCC increased slightly from 0.85 per 100,000 person-years in 1997-1998 to 1.13 per 100,000 person-years in 2017-2018 (AAPC = 1.01; 95% CI: 0.24-1.79). The 5-year relative survival of penile SCC did not change substantially, whereas the mortality tended to decrease. CONCLUSION: Penile SCC is increasing slightly in Denmark, while a pronounced increase in the incidence of high-grade PeIN is seen. The 5-year relative survival from penile cancer was relatively stable over time. Increasing exposure to HPV infection at the population level may have contributed to the observed increase in PeIN and penile SCC. Awareness of HPV may also have contributed to the increased detection of PeIN.

Trends in rectal cancer incidence, relative survival, and mortality in Denmark during 1978-2018.

OBJECTIVE: Rectal cancer is common in developed countries, though incidence varies globally. We assessed time trends in incidence, relative survival and mortality in Denmark. METHODS: Rectal cancer cases ( N = 50 461) diagnosed in 1978-2018 were identified in the Danish Cancer Registry. We calculated age-standardized incidence rates, overall and according to sex and age. Average annual percentage changes (AAPC) were estimated using Poisson regression. We estimated 5-year relative survival and evaluated the effect of age, calendar year of diagnosis, sex and stage of disease on mortality using the Cox proportional hazards model. RESULTS: The incidence of rectal cancer tended to decrease in all age groups and both sexes during 1978-1997, but increased since 1998, more in men (AAPC = 2.05%; 95% CI,1.80; 2.31) than in women (AAPC = 0.99%; 95% CI,0.68; 1.30). It increased in men until 79 years and in women up to 59 years. Mortality decreased over time when adjusting for age, stage and sex. Overall, men had the highest 5-year mortality after adjusting for age, calendar period and stage. Five-year relative survival improved (1978-2018) for all stages. Initially, the overall 5-year relative survival tended to be better for women, but in recent years, it has been similar in both sexes. CONCLUSION: Incidence of rectal cancer increased in the last two decades, most markedly in women 59 years and younger. Mortality decreased when adjusting for age and stage. Relative survival improved over time more for men than for women, so in recent years, it has been virtually identical in men and women.

The prognostic significance of HPV, p16, and p53 protein expression in vaginal cancer: A systematic review.

INTRODUCTION: Human papillomavirus (HPV), p16, and p53 have been investigated as prognostic markers in various HPV-related cancers. Within the field of vaginal cancer, however, the evidence remains sparse. In this systematic review, we have compiled the presently published studies on the prognostic significance of HPV and immunohistochemical expression of p16 and p53 among women with vaginal cancer. MATERIAL AND METHODS: We conducted a systematic search of PubMed, Embase, and Cochrane Library to identify relevant studies published until April 2021. We included studies reporting survival after histologically verified vaginal cancers tested for HPV, p16, and/or p53. Survival outcomes included overall survival, disease-free survival, disease-specific survival, and progression-free survival. RESULTS: We included a total of 12 studies. The vast majority of vaginal cancer cases included in each study were squamous cell carcinomas (84%-100%). Seven studies reported survival after vaginal cancer according to HPV status, and the majority of these studies found a tendency towards improved survival for women with HPV-positive vaginal cancer. Three out of four studies reporting survival according to p16 status found an improved survival among women with p16-positive vaginal cancer. For p53, only one of six studies reported an association between p53 expression and survival. CONCLUSIONS: This systematic review suggests that women with HPV- and p16-positive vaginal cancer have an improved prognosis compared with those with HPV- or p16-negative vaginal cancer. Results for p53 were varied, and no conclusion could be reached. Only 12 studies could be included in the review, of which most were based on small populations. Hence, further and larger studies on the prognostic impact of HPV, p16, and p53 in vaginal cancer are warranted.

Risk of cervical intraepithelial neoplasia grade 2 or worse after conization in relation to HPV vaccination status.

Human papillomavirus (HPV) is essential for developing cervical cancer and precancerous lesions. Currently, three vaccines are available, which are effective as prophylaxis against HPV infection, however, limited knowledge exists about the possible effect of vaccinating women treated with conization to prevent recurrence. The aim of our study was to examine the risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) after conization according to HPV vaccination status. Using Danish nationwide registries, we identified women diagnosed with CIN3 on the cone (2006-2012) and their HPV vaccination status. Vaccinees were defined as women vaccinated between 3 months before until 1 year after conization. The women were followed from 1 year after conization until diagnosis of CIN2+, conization, death, emigration or end of follow-up. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of CIN2+ comparing vaccinees with nonvaccinees. The HR was adjusted for age, histology on cone, education, year of conization, repeat conizations and CIN2+ lesions between conization and start of follow-up. Altogether 17,128 women were included (2,074 vaccinees). There was a statistically nonsignificant lower risk of CIN2+ among vaccinees (HRadjusted = 0.86, 95% CI: 0.67-1.09). Women vaccinated 0-3 months before tended to have a slightly lower HR of CIN2+ (HRadjusted = 0.77, 95% CI: 0.45-1.32) than women vaccinated 0-12 months after conization (HRadjusted = 0.88, 95% CI: 0.67-1.14), although not statistically significantly different. Our results add to the current knowledge about the potential clinical effect of vaccination as an adjunct to conization of high-grade cervical neoplasia to decrease risk of recurrence.

Prevalence and type distribution of human papillomavirus in squamous cell carcinoma and intraepithelial neoplasia of the vulva.

In this updated systematic review and meta-analysis, we estimate the pooled prevalence of human papillomavirus (HPV) DNA and HPV type distribution in squamous cell carcinoma of the vulva (vulvar cancer) and vulvar intraepithelial neoplasia (VIN). PubMed, Embase and Cochrane Library databases were used to identify studies published between 1990 and 2015 and using a PCR-based or hybrid capture test to evaluate the presence of HPV DNA in vulvar cancer or VIN. Pooled estimates of the HPV prevalence with corresponding 95% confidence intervals (CI) were calculated based on a random effects model. The I2 statistic was used to describe the amount of heterogeneity. In meta-regression analyses, potential sources of heterogeneity were evaluated. We identified 92 eligible papers, comprising altogether 5,015 cases of vulvar cancer (64 papers) and 2,764 cases of VIN (48 papers). The pooled prevalence of HPV in vulvar cancer was 39.7% (95% CI: 35.1-44.4%). Overall, 76.3% (95% CI: 70.1-82.1%) of VIN lesions tested HPV-positive, while the HPV prevalence in new subcategories of VIN, uVIN and dVIN, was 86.2% (95% CI: 73.5-95.5%) and 2.0% (95% CI: 0-10.0%), respectively. Substantial between-study heterogeneity was observed (vulvar cancer: I2 = 88.4%; VIN: I2 = 90.7%) with the largest variation between geographical regions. Among HPV-positive cases, the predominant high-risk HPV type was HPV16, followed by HPV33 and HPV18. HPV6 was detected as a single infection in a small subset of VIN and vulvar cancer samples. Thus, HPV vaccination targeting these HPV types may prevent a substantial number of vulvar lesions.