Human papillomaviruses (HPV) consist of more than 100 different viruses. Some types of HPV cause warts on the hands or feet; others cause genital warts; and some have been linked with cancer, most notably cervical cancer.

Gardasil prevents infection with four types of HPV—types 6, 11, 16, and 18. HPV types 16 and 18 cause roughly 70% of all cases of cervical cancer, and HPV types 6 and 11 account for roughly 90% of genital warts. Gardasil was approved by the U.S. Food and Drug Administration (FDA) in June 2006.

Previous studies have shown that Gardasil protects against high-grade precancerous changes to the cervix, vulva, and vagina. High-grade changes are those that are the most likely to progress to invasive cancer if not treated.

Less is known about how vaccination will affect the risk of low-grade precancerous changes (cervical, vulvar, or vaginal intraepithelial neoplasia grade 1). Although many low-grade changes will resolve on their own without treatment, these changes require follow-up and may be a source of anxiety and expense.

To further understand how effectively Gardasil may protect against genital warts as well as low-grade lesions, researchers conducted a study including almost 18,000 women from around the world. Participants were ages 16-26 years at enrollment.

One group of women was given three doses of Gardasil, and the other group received a placebo. HPV-related outcomes were compared between groups:

• Gardasil was 96-100% effective in preventing low-grade lesions or genital warts related to the HPV types the vaccine is targeted against (types 6, 11, 16, and 18).
• When looking at all lesions regardless of HPV type, the efficacy of Gardasil was 30% for low-grade cervical changes; 75% for low-grade vulvar changes, 48% for low-grade vaginal changes, and 83% for genital warts.
• Protection was sustained through the four years of follow-up.

The researchers concluded that Gardasil provides sustained protection against low-grade cervical, vulvar, and vaginal lesions related to HPV types 6, 11, 16, and 18. Because such lesions affect patient health and healthcare cost and may cause anxiety, preventing them could be an important contribution to public health.

Reference: The FUTURE I/II Study Group. Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial. BMJ. 2010;341:c3493.

In 2010, an estimated 217,000 U.S. men will be diagnosed with prostate cancer and 32,000 will die of the disease.[1]

Men 50 years of age or older are often offered prostate-specific antigen (PSA) testing for the early detection of prostate cancer. The test may be offered at a younger age to men at high risk of prostate cancer. The PSA test measures proteins that are produced and shed by the prostate. PSA levels tend to be elevated when prostate cancer is present, but levels can also be elevated in benign (non-cancerous) conditions affecting the prostate.

For men with elevated PSA levels (often defined as a PSA level higher than 4.0 ng/mL), a prostate biopsy may be recommended in order to determine whether or not prostate cancer is present. Prostate cancer can also be present among men with lower PSA levels, however, which has led some researchers to suggest lowering the threshold for biopsy in order to detect more cancers.

A potential concern with lowering the threshold for biopsy is that it could increase the overdiagnosis and overtreatment of prostate cancer. Many prostate cancers will never cause health problems during a man’s lifetime. Treatment of these indolent cancers exposes men to the risk of treatment side effects without providing a health benefit; this constitutes “overtreatment.”  Unfortunately, although some prostate cancers can be classified as “low-risk” on the basis of tumor stage, PSA level, and Gleason score, it is still not possible to know for certain which prostate cancers require treatment and which don’t.

To explore the characteristics and treatment of prostate cancers among men with low PSA levels, researchers evaluated information from a large U.S. cancer database: the Surveillance, Epidemiology, and End Results (SEER) system.[2] Information was available for almost 124,000 men diagnosed with prostate cancer between 2004 and 2006.

• 14% of the prostate cancer diagnoses occurred among men with a PSA level of 4.0 ng/mL or lower.
• 54% of the prostate cancer cases among men with low PSA levels were considered “low-risk” on the basis of tumor stage, PSA level, and Gleason score. By comparison, among men with PSA levels between 4.1 and 10.0 ng/mL, 48% of prostate cancers were considered low risk.
• 77% of prostate cancer patients with low PSA levels were treated aggressively with either radical prostatectomy or radiation therapy. This is similar to the rate of treatment among men with higher PSA levels.

The researchers conclude: “Most men diagnosed as having prostate cancer with a PSA threshold below 4.0 ng/mL had low risk disease but underwent aggressive local therapy. Lowering the biopsy threshold but retaining our inability to distinguish indolent from aggressive cancers might increase the risk of overdiagnosis and overtreatment.”

References:

[2] Shao Y-H, Albertsen PC, Roberts CB et al. Risk profiles and treatment patterns among men diagnosed as having prostate cancer and a prostate-specific antigen level below 4.0 ng/mL. Archives of Internal Medicine. 2010;170:1256-1261

Workers in certain occupations may face an increased risk of cancer due to exposures that they encounter on the job. Exposure to radiation, potentially hazardous chemicals, or second-hand smoke may all carry risk. Some studies have linked work as a painter with an increased risk of bladder and lung cancer.

Using data from multiple studies, researchers associated with the International Agency for Research on Cancer (IARC) evaluated the risk for bladder cancer associated with occupational exposure to painting.

• Overall, occupational exposure to painting increased the risk of bladder cancer by 25%. The elevated risk remained after taking into consideration smoking and other risk factors.
• The longer the duration of exposure to painting, the greater the risk.

The IARC has classified occupational exposure as a painter as “carcinogenic to humans,” based primarily on increases in risk of bladder cancer and lung cancer. Although the researchers say that the increase in bladder cancer risk is “modest,” they note that any elevation is noteworthy “because several million people are employed as painters worldwide.”

Reference: Guha N, Steenland NK, Merletti F, et al. Bladder cancer risk in painters: a meta-analysis. Occupational and Environmental Medicine. 2010 Aug;67(8):568-73.

Metastatic breast cancer refers to cancer that has spread to distant sites in the body. Chemotherapy is a cornerstone of therapy for metastatic breast cancer; however, novel therapeutic approaches are now providing more targeted methods of treatment.

Avastin is an agent targeted against the vascular endothelial growth factor (VEGF). VEGF is involved in the growth and spread of cancer cells, which Avastin reduces or prevents. Avastin is approved for the treatment of some colon, kidney, brain, and lung cancers as well as breast cancer.

The ODAC is a committee that makes recommendations to the FDA regarding approval of drugs for use in oncology. Although the FDA is not required to follow recommendations of the ODAC, it often does.

The committee’s current recommendation that Avastin combined with chemotherapy not be used as initial therapy in advanced breast cancer is based on their review of three studies involving more than 2,400 patients. Their decision is based on evaluating the risks and benefits of treatment with the combination of Avastin and chemotherapy compared with chemotherapy alone. The initial study that led to the accelerated approval from the FDA in 2008 resulted in a progression-free survival improvement of 5.5 months with the addition of Avastin to paclitaxel compared with paclitaxel alone. Two subsequent studies showed smaller improvements in progression-free survival. There is still no evidence, however, that Avastin improves overall survival among women with breast cancer.

Avastin is still currently available for advanced breast cancer patients; the FDA is expected to make a decision on whether or not this should remain an option for initial treatment of this disease by September 17, 2010. The decision will not affect use of Avastin for other cancers.

Reference: Genentech press release. Genentech Provides Update From Avastin FDA Advisory Committee Meeting. Accessed July 2010.

Squamous cell carcinoma of the penis is relatively uncommon in the United States, with about 1,400 cases diagnosed annually. The disease, however, is more prevalent in Africa, South America, and Asia, and an estimated 26,000 new cases are diagnosed annually worldwide. Men with regional lymph node involvement have low survival rates. Because of its rarity, there is limited information regarding multimodality treatment for metastatic penile cancer.

The current study involved 30 men with Stage III or IV penile cancer with regional lymph node involvement but no distant metastases. All men underwent four courses of neoadjuvant chemotherapy (prior to surgery) with a combination of Taxol/Ifex/Platinol. Fifty percent of men experienced an objective response from the therapy, and 73% subsequently underwent surgery.

After a median follow-up of 34 months, nine patients (30%) remained alive and free of recurrence and two patients had died of other causes without recurrence. The researchers concluded that a neoadjuvant combination of Taxol/Ifex/Platinol was effective in terms of the conventional response rate, time to disease progression, and overall survival. The regimen produced a pathologic complete response in 10% of patients. The researchers recommend the neoadjuvant regimen for men with regional metastatic penile cancer.

Reference:

Adult ALL is a malignant disease or cancer of the blood characterized by the rapid uncontrolled growth of abnormal, immature white blood cells known as lymphoblasts. There are approximately 5,000 new cases of adult ALL each year in the United States, with approximately 1,500 deaths. Up to 40% of adults with ALL have Ph+ ALL. Adults with Ph+ ALL usually receive Gleevec® (imatinib) in the induction regimen.

Sprycel is a tyrosine kinase inhibitor that may be used for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy. Previous studies have suggested that Sprycel is also effective for first-line therapy of Ph+ ALL. Researchers from Italy reported that Sprycel monotherapy resulted in a 100% complete hematologic remission rate in 36 patients with newly diagnosed Ph+ ALL.[2] Researchers affiliated with the European Working Group on Adult ALL (EWALL) reported a 100% complete hematologic remission rate for 22 patients with newly diagnosed Ph+ ALL treated with Sprycel plus chemotherapy.[3] Studies have been ongoing to determine the optimal incorporation of Sprycel into a tolerable regimen for induction, consolidation, and maintenance therapies.

In the current Phase II study, researchers from M. D. Anderson Cancer Center evaluated 35 newly diagnosed adult patients with Ph+ ALL. Patients initially underwent treatment with a combination of Sprycel, hyperCVAD, and high-dose cytarabine and methotrexate. Once patients achieved a complete remission, maintenance therapy consisted of daily Sprycel indefinitely with monthly vincristine and prednisone for two years. The researchers reported that 33 of the 35 patients (94%) achieved a complete remission with two patients being lost before assessment due to infection. This is an initial report of an ongoing study, and at a median follow up of 14 months survival endpoints have not yet been reached. However, the estimated two-year survival is 64%. So far, grade 3 and 4 side effects include bleeding, fluid build-up in the lungs (pleural effusion), and fluid around the heart (pericardial effusion).

These researchers concluded that the combination of Sprycel and chemotherapy is “effective in achieving long term remissions in patients with newly diagnosed Ph+ ALL.” The overall and disease-free survival data will provide additional efficacy data for this promising combination for newly diagnosed Ph+ ALL patients.

References:

[2] Foa R, Vitale A, Guarini A, et al. Dasatinib monotherapy effective and feasible as first-line treatment of adult Philadelphia-chromosome positive acute lymphoblastic leukemia: Final results of the GIMEMA LAL1205 study. Blood. 2008;112:119, abstract number 305

[3] Cayuela J-M, Recher C, Leguay T, et al. Dasatinib (Sprycel®) and chemotherapy for first-line treatment of elderly patients with de Novo Philadelphia Positive ALL: Results of the first 22 patients included in the EWALL-PH-01 Trial (on behalf of the European Working Group on Adult ALL (EWALL). Blood. 2008;112:1004, abstract 2920.

The survival rate for childhood cancer is high, with 80% of children and adolescents surviving five or more years. Prior studies have demonstrated that during the first 20 years following diagnosis, survivors of childhood cancer have an increased risk of dying from a second cancer or other diseases when compared with the general population.  Researchers recently investigated whether this elevated risk continued to be present 25 years following diagnosis of childhood cancer.

In this British study, researchers followed 17,981 childhood cancer survivors diagnosed at the age of 15 or younger to determine how their risk of premature death resulting from chronic disease compared with the general population. The childhood cancer survivors included in this analysis survived five years or longer, were diagnosed between 1940 and 1991, and were followed through 2006.

• Overall, the number of early deaths in the childhood cancer survivor population was 11 times that of the general population.
• Rates of premature death declined as time elapsed but were still threefold higher than the general population, even 45 years after diagnosis.
• Compared with the general population, childhood cancer survivors experienced a higher risk of premature death due to a second cancer, circulatory disease, or pulmonary disease that persisted beyond 25 years following diagnosis.

The researchers concluded that “survivors diagnosed more than 25 years ago are currently most at risk of dying of a second primary cancer or circulatory disease, yet these survivors are much less likely to be actively followed up than those diagnosed more recently. The findings of this study suggest that survivors should be able to access health care intervention programs even many years after survival from their first cancer.”

Reference:

Many cases of melanoma are thought to be related to sun exposure. Preventative measures include avoidance of sun exposure, avoidance of tanning beds, and the use of sunscreens. Many educational initiatives have been deployed throughout the country to raise the awareness of the rising melanoma epidemic in an effort to improve screening and prevention. In a prior study evaluating trends in melanoma incidence as related to UV index and lower latitude, no link to melanoma incidence in Hispanics or African Americans was demonstrated.[2]

In this study researchers evaluated data from the Florida Cancer Data System and compared it with the data from the National Cancer Institute’s national database of cancer statistics called the Surveillance, Epidemiology and End Results (SEER) Program. Melanoma incidence was evaluated for age, sex, and ethnicity and compared in order to identify trends in Florida, which is considered a higher-risk region for melanoma in the United States.

• Male Hispanic Floridians were reported to experience a 20% higher incidence of melanoma compared with male Hispanics in the national database.
• Female Hispanic Floridians were reported to experience a significantly lower incidence of melanoma compared with female Hispanics in the national database.
• Female African-American Floridians (non-Hispanic) were reported to experience a 60% higher incidence of melanoma compared with African-American females in the national database.

This study highlights the importance of education about the early signs of melanoma for all patient populations, regardless of race. Although Hispanics and African Americans have a lower risk of developing melanoma, they tend to present with more-advanced disease.

Reference:

[2] Eide MJ and Weistock MA. Association of UV Index, Latitude, and Melanoma Incidence in Nonwhite Populations— US Surveillance, Epidemiology, and End Results (SEER) Program, 1992 to 2001. Archives of Dermatology. 2005;141:477-481.

The nasopharynx is the area above the soft palate (roof of the mouth) and behind the nose. Nasopharyngeal cancer is considered a type of head and neck cancer. Approximately 40,000 people in the United States are diagnosed with head and neck cancer every year.

Regionally advanced nasopharyngeal cancer refers to cancer that has spread to nearby tissues or lymph nodes. Standard treatment typically includes radiation therapy and chemotherapy. Data are limited, however, on toxicity (side effects) and non-cancer-related mortality associated with radiation plus chemotherapy in this patient population.

A recent study compared survival and toxicity of radiation plus chemotherapy with that of radiation alone in patients with regionally advanced nasopharyngeal carcinoma. Chemotherapy agents used in the radiation-plus-chemotherapy group included Platinol® (cisplatin) and fluorouracil.

At five years, patients who received radiation plus chemotherapy had significantly improved failure-free and progression-free survival rates compared with those who received radiation only. As well, deaths due to cancer progression were significantly lower for the radiation-plus-chemotherapy group. The survival advantages of radiation plus chemotherapy, however, were reduced by increased toxicity and a higher rate of non-cancer deaths: once these outcomes were accounted for, overall survival was similar between both groups.

It appears that although adding chemotherapy to radiation for treatment of advanced nasopharyngeal carcinoma does significantly reduce deaths due to cancer progression, the increase in deaths from other causes ultimately reduces the survival advantage. In other words, overall survival is similar between radiation plus chemotherapy and radiation alone.

Reference: Lee A, Tung S, Chua D, et al. Randomized trial of radiotherapy plus concurrent–adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma. Journal of the National Cancer Institute [early online publication]. July 15, 2010.

Many chemicals and environmental contaminants are thought to pose a risk for cancer, but information about risk to humans is often limited. Recently, the President’s Cancer Panel issued a report outlining the environmental risks for the disease.[2] There are some common chemicals and occupational agents for which the evidence of carcinogenic toxicity is suggestive but inconclusive.

The American Cancer Society, National Institute for Occupational Safety and Health, National Institute of Environmental Health Sciences, and the National Cancer Institute collaborated to sponsor a report that identified 20 potential causes of cancer that may warrant further research due to widespread human exposure and suggestive evidence from animal studies. Below is the list, which includes 19 common chemicals, plus one environmental condition:

• Lead and lead compounds
• Indium phosphide
• Cobalt with tungsten carbide
• Titanium dioxide
• Welding fumes
• Refractory ceramic fibers
• Diesel exhaust
• Carbon black
• Styrene-7, 8-oxide, and styrene
• Propylene oxide
• Formaldehyde
• Acetaldehyde
• Dichloromethane, methylene chloride (DCM)
• Trichloroethylene (TCE)
• Tetrachloroethylene (perc, tetra, PCE)
• Chloroform
• Polychlorinated biphenyls (PCBs)
• Di (2-ethylhexyl) phthalate (DEHP)
• Atrazine
• Shift work

In order to determine the risk to humans, the report recommends additional research on each of these potential contributors to cancer.

Reference:

[2] 2008-2009 President’s Cancer Panel. Reducing environmental cancer risk: What we can do now.  U.S. Department of Health and Human Services; National Institutes of Health; National Cancer Institute. April 2010. Accessed online: http://deainfo.nci.nih.gov/advisory/pcp/pcp08-09rpt/PCP_Report_08-09_508.pdf.