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Johan Lindholm

Other affiliations: Karolinska Institutet
Bio: Johan Lindholm is an academic researcher from Karolinska University Hospital. The author has contributed to research in topics: Cancer & Epidermoid carcinoma. The author has an hindex of 25, co-authored 59 publications receiving 3767 citations. Previous affiliations of Johan Lindholm include Karolinska Institutet.


Papers
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Journal ArticleDOI
TL;DR: The incidence of HPV‐positive cancers is still increasing in the County of Stockholm, suggesting an epidemic of a virus‐induced carcinoma, with soon practically all tonsillar SCC being HPV positive, as in cervical cancer.
Abstract: In the county of Stockholm, between 1970 and 2002, we have previously reported a 3-fold parallel increase in the incidence of tonsillar squamous cell carcinoma (SCC) and the proportion of human papillomavirus (HPV) positive tonsillar SCC. Here, we have followed the above parameters in all patients (n = 120) diagnosed with tonsillar SCC during 2003-2007 in the same area, and also in correlation to our previous data. Ninety-eight pretreatment biopsies were available and presence of HPV DNA and HPV-16 E6 and E7 RNA were tested by polymerase chain reaction (PCR) and RT-PCR. Incidence data were obtained from the Swedish Cancer Registry. Data reported from 1970 to 2002 were also obtained for comparison. HPV DNA was present in 83 of 98 (85%) of the tonsillar SCC biopsies from 2003 to 2007 and 77 of these were HPV-16 positive. HPV-16 E6 and E7 RNA were found in 98% of 52 analyzed HPV-16 positive cases. The proportion of HPV-positive cancers had significantly increased both from 1970 to 2007 (p < 0.0001) as well from 2000 to 2007 (p < 0.01), with 68% (95% confidence interval (CI), 53-81) 2000-2002; 77% (95% CI, 63-87) 2003-2005; and 93% (95% CI, 82-99) 2006-2007. The incidence rate of HPV-positive tumors almost doubled each decade between 1970 and 2007, in parallel with a decline of HPV-negative tumors. In conclusion, the incidence of HPV-positive cancers is still increasing in the County of Stockholm, suggesting an epidemic of a virus-induced carcinoma, with soon practically all tonsillar SCC being HPV positive, as in cervical cancer.

706 citations

Journal ArticleDOI
TL;DR: A highly significant and parallel increase both in the incidence of tonsillar cancer and the proportion of HPV‐positive tumors is demonstrated, which should definitely influence future preventive strategies as well as treatment for this type of cancer.
Abstract: Smoking and alcohol are well-known etiological factors in tonsillar cancer. However, as in cervical cancer, human papillomavirus (HPV) is currently found in a sizable proportion of tonsillar cancer. Recent reports from the U.S. and Finland show an increase in the incidence of tonsillar cancer, without a parallel rise in smoking and alcohol consumption. This study investigates whether the incidence of tonsillar cancer has also changed in Sweden and whether a possible explanation of the increase is a higher proportion of HPV-positive tonsillar cancer. The incidence of tonsillar cancer between 1970 and 2002 in the Stockholm area was obtained from the Swedish Cancer Registry. In parallel, 203 pretreatment paraffin-embedded tonsillar cancer biopsies taken during 1970-2002 from patients in the Stockholm area were tested for presence of HPV DNA by PCR. The incidence of tonsillar cancer increased 2.8-fold (2.6 in men and 3.5 in women) from 1970 to 2002. During the same period, a significant increase in the proportion of HPV-positive tonsillar cancer cases was observed, as it increased 2.9-fold (p < 0.001). The distribution of HPV-positive cases was 7/30 (23.3%) in the 1970s, 12/42 (29%) in the 1980s, 48/84 (57%) in the 1990s and 32/47 (68%) during 2000-2002. We have demonstrated a highly significant and parallel increase both in the incidence of tonsillar cancer and the proportion of HPV-positive tumors. Hence, HPV may play an important role for the increased incidence of tonsillar cancer. This should definitely influence future preventive strategies as well as treatment for this type of cancer.

460 citations

Journal ArticleDOI
TL;DR: Cylindrical APE performed in the prone position for low rectal cancer removes more tissue around the tumor that leads to a reduction in CRM involvement and intraoperative perforations, which should reduce local disease recurrence.
Abstract: Purpose Abdominoperineal excision (APE) of the rectum and anus for rectal cancer continues to have greater local recurrence and poorer survival than that seen following anterior resection. Changing to an extended prone perineal dissection results in a more cylindrical specimen and should improve outcomes. Patients and Methods One hundred twenty-eight specimens from patients who underwent APE that was performed for potentially curable primary rectal adenocarcinoma were dissected according to standard protocol in Leeds and Stockholm between 1997 and 2007 and were studied. Tissue morphometry was performed on the cross sectional photographs of 93 patient cases. Results The cylindrical technique removed more tissue in the distal rectum and in all slices that contained tumor compared with the standard operation (both P < .0001). Greater distance was observed from the muscularis propria or internal sphincter to the anterior, posterior, and lateral resection margins (all P < .0001). This was associated with lower...

376 citations

Journal ArticleDOI
TL;DR: HPV‐16 is mainly episomal in tonsillar cancer, the viral load showed a wide distribution and the clinical outcome in this study was better when the HPV load was higher.
Abstract: The aim of our study was to investigate the physical state and the viral load of HPV-16 in tonsillar cancer and to correlate these findings with clinical outcome. To distinguish between integrated and episomal forms of HPV, 22 fresh-frozen tonsillar cancer samples were analysed by a method based on restriction enzyme cleavage, ligation and PCR (rliPCR). HPV-16 was detected in 11/22 and HPV-33 in 1/22 of the cancers, hence 12/22 (55%) of the tumours were HPV positive. Only extrachromosomal forms of HPV-16 were observed. Full-length episomal HPV was detected exclusively in 7/11 of the cancers, whereas both full-length and deleted forms of episomal HPV-16 were found in parallel in 2 other tumours. In 1 tumour only a deleted episomal form of HPV-16 was present. In the remaining HPV-16 positive tumour both full-length episomal as well as an 11 kbp PCR product were detected and if the 11 kbp product contained integrated HPV, or was off-size linearised episomal could not be determined. In 2 cervical cancer controls, HPV-16 was integrated and could be chromosome located. HPV-16 was quantified by real-time PCR and most tonsillar cancers contained between 10 to a few hundred copies of HPV per beta-actin. The 6 patients with tumour sections with > or =190 HPV-16 copies/beta-actin remained tumour free (p = 0.026) and had a better survival rate (p = 0.039) when compared to the 5 patients with tumours sections with < or =60 HPV-16 copies/beta-actin. In conclusion, HPV-16 is mainly episomal in tonsillar cancer. The viral load showed a wide distribution and the clinical outcome in our study was better when the HPV load was higher.

244 citations

Journal ArticleDOI
TL;DR: The incidence of base of tongue cancer, as well as the proportion of HPV‐positive tumors, has increased in Sweden during the study period, suggesting that HPV may contribute to this increase.
Abstract: Numerous reports have shown that the incidence for oropharyngeal cancer is increasing and that human papillomavirus (HPV) is a risk factor. However, few studies have investigated the specific subsites of the oropharynx. Following our previous research on tonsillar cancer, we assessed the increase in the incidence of base of tongue cancer and the prevalence of HPV in this disease. Between 1998 and 2007, 109 patients were diagnosed for base of tongue cancer in Stockholm county. Ninety-five paraffin-embedded diagnostic tumor biopsies from patients were obtained and tested for HPV, both by general HPV PCR and HPV-16/HPV-33 type-specific PCR. Expression of HPV-16 RNA was analyzed to confirm E6 and/or E7 expression. Incidence data were obtained from the Swedish Cancer Registry. An overall increase in the incidence of base of tongue cancer from 0.15/100,000 person-years during 1970-1974 to 0.47/100,000 person-years during 2005-2007 was found in Sweden. The prevalence of HPV in base of tongue cancer in Stockholm county increased from 58% during 1998-2001 to 84% during 2004-2007 (p < 0.05). In the HPV-positive tumors, HPV-16 dominated (86%) but interestingly, HPV33 was detected in as many as 10%. E6 and/or E7 RNA were found in 85% of the samples tested. The incidence of base of tongue cancer, as well as the proportion of HPV-positive tumors, has increased in Sweden during the study period, suggesting that HPV may contribute to this increase.

213 citations


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TL;DR: A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination, and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake.
Abstract: The global burden of cancer continues to increase largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors, particularly smoking, in economically developing countries. Based on the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.6 million cancer deaths are estimated to have occurred in 2008; of these, 56% of the cases and 64% of the deaths occurred in the economically developing world. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% of the total cancer cases and 14% of the cancer deaths. Lung cancer is the leading cancer site in males, comprising 17% of the total new cancer cases and 23% of the total cancer deaths. Breast cancer is now also the leading cause of cancer death among females in economically developing countries, a shift from the previous decade during which the most common cause of cancer death was cervical cancer. Further, the mortality burden for lung cancer among females in developing countries is as high as the burden for cervical cancer, with each accounting for 11% of the total female cancer deaths. Although overall cancer incidence rates in the developing world are half those seen in the developed world in both sexes, the overall cancer mortality rates are generally similar. Cancer survival tends to be poorer in developing countries, most likely because of a combination of a late stage at diagnosis and limited access to timely and standard treatment. A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination (for liver and cervical cancers), and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake. Clinicians, public health professionals, and policy makers can play an active role in accelerating the application of such interventions globally.

52,293 citations

Journal ArticleDOI
TL;DR: A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests.
Abstract: Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests.

23,203 citations

Journal ArticleDOI
TL;DR: Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer and the risk of death significantly increased with each additional pack-year of tobacco smoking.
Abstract: Background Oropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown. Methods We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a randomized trial comparing accelerated-fractionation radiotherapy (with acceleration by means of concomitant boost radiotherapy) with standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck. Proportional-hazards models were used to compare the risk of death among patients with HPV-positive cancer and those with HPV-negative cancer. Results The median follow-up period was 4.8 years. The 3-year rate of overall survival was similar in the group receiving accelerated-fractionation radiotherapy and the group receiving standard-fractionation radiotherapy (70.3% vs. 64.3%; P = 0.18; hazard ratio for death with accelerated-fractionation radiotherapy, 0.90; 95% confidence interval [CI], 0.72 to 1.13), as were the rates of high-grade acute and late toxic events. A total of 63.8% of patients with oropharyngeal cancer (206 of 323) had HPV-positive tumors; these patients had better 3-year rates of overall survival (82.4%, vs. 57.1% among patients with HPV-negative tumors; P<0.001 by the log-rank test) and, after adjustment for age, race, tumor and nodal stage, tobacco exposure, and treatment assignment, had a 58% reduction in the risk of death (hazard ratio, 0.42; 95% CI, 0.27 to 0.66). The risk of death significantly increased with each additional packyear of tobacco smoking. Using recursive-partitioning analysis, we classified our patients as having a low, intermediate, or high risk of death on the basis of four factors: HPV status, pack-years of tobacco smoking, tumor stage, and nodal stage. Conclusions Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer. (ClinicalTrials.gov number, NCT00047008.)

5,263 citations

01 Jan 2002
TL;DR: This list includes tumours of undefined neoplastic nature, which are of uncertain differentiation Bone Tumours, Ewing sarcoma/Primitive neuroedtodermal tumour, Myogenic, lipogenic, neural and epithelial tumours, and others.

4,185 citations