Cervical Cancer in Women, no simple proposition !

Preventing cancer, as we know, is no simple proposition.

We have clues about what practices may help—say, exercising regularly, nixing cigarettes, and eating real, healthful food. But when we see even hyper-fit celebrities like Lance Armstrong fall victim, it’s easy to wonder whether there’s much we can do to prevent tumors in our own bodies.

But when it comes to cervical cancer in women, the answer in many cases is a resounding “yes.”

So much so, in fact, that the Centers for Disease Control has billed this disease “the most preventable female cancer.”

One of the most important tools?

That mainstay of gynecological exams, known as the Pap test.

Historically, cervical cancer was one of the most common causes of cancer death in American women.

But thanks to widespread adoption of Pap tests in Western countries during the 1950s, cancer death rates plummeted a whopping 74 percent among American women between 1955 and 1992.

According to the CDC, 6 of 10 cervical cancers occur in women who have never received a Pap test or have not been tested in the past five years. By contrast, about 90 percent of women whose cervical cancer was detected by a Pap test will survive.

Human papillomavirus, shown in this electron micrograph, is the leading cause of cervical cancer. (Credit: NCI)

Problem solved, right? Hardly.

Worldwide, cervical cancer remains a leading cause of death in women who live in lower-resource areas where screening tests are not as readily available, with the highest incidence rates in Central America and sub-Saharan Africa.

The disease also remains far more common in Hispanic women and Vietnamese-American women than in other U.S. ethnic groups because of lower screening rates, some of which can be explained by diverse cultural beliefs. Our researchers are working with these communities to try to improve detection.

Another emerging tool is a relatively new vaccine called Gardasil. Now geared toward members of both genders aged 9-26, this drug offers protection against the types of human papillomavirus (HPV) that cause 70 percent of all cervical cancers.

Our own Dr. Denise Galloway was among the researchers who spent decades laying the groundwork for this important vaccine.

If you know someone who isn’t getting regular Pap tests because of financial concerns, learn about a government program that can help.

To learn more about cervical cancer, visit our disease information page.

The Galloway lab is focused on ‘the role that small DNA viruses play in cancer’, including the high risk human papillomaviruses (HPV) in anogenital cancers, genus beta HPVs in squamous cell skin cancers, and the Merkel cell polyomavirus (MCPyV) in Merkel cell carcinomas.

We have taken a broad based approach that includes mechanistic studies into how the viral oncoproteins contribute to neoplasia, and molecular epidemiologic studies into the natural history of viral infections and risk factors that are associated with the development of these cancers.

We have sought to determine how the HPV 16 E6 and E7 oncoproteins disrupt the cell cycle checkpoints that normally maintain genomic integrity, and how E6/E7 facilitates the immortalization of primary human cells in culture.

In ongoing studies, we are interested in how the E6 protein regulates expression of hTERT, the catalytic sub-unit of telomerase. HPV 16 E6 targets two isoforms of NFX1, promoting degradation of the NFX1-91 transcriptional repressor, and stabilizing the hTERT mRNA in concert with NFX1-123. We are also studying the genus beta E6 proteins, investigating the mechanisms by which they block apoptosis, and disrupt p53 activity by targeting the coactivator p300.

To aid in epidemiologic studies we have developed serologic assays to detect and characterize papillomavirus and polyomavirus-specific antibodies. The recent establishment of multiplex assays in our lab is affording a more comprehensive assessment of the prevalence of HPV and HPyV infections. In collaborative studies we are assessing HPV antibodies following natural infection in cohorts of young and mid-adult women, young men, and vaccinees (Dr. Laura Koutsky). We are determining whether markers of genus beta HPV infections predict the development of skin cancer in organ transplant recipients (Drs Margaret Madeleine, Dan Berg, Connie Davis and Peggy Porter), and similarly the association of MCPyV antibodies in Merkel cell carcinoma (Dr. Paul Nghiem).

In addition to viral oncogenes, we have studied the contributions of cellular oncogenes such as c-Myc and Ha-Ras to immortalization of human cells. In collaboration with Dr. Carla Grandori we have developed expression signatures for cells expressing these oncogenes and are examining how the RecQ helicases facilitate proliferation in c-Myc expressing cells and tumors. PUBLICATIONS

Anne Broache,
Quest science writer

 

 

 

RELATED REFERENCES – GLOBAL:

NORTH AMERICA

USA – National Library of Medicine
CANADA – Journal of Obstetrics and Gynaecology, Canada
CANADA – Where Can I Get a Pap Test?

EUROPE

Europe PubMed Central

ASIA

THAILAND – Bumrungrad Hospital

AUSTRALIA

NSW – Cervical Screening Program

AFRICA

South Africa – South African HPV Advisory Board

SOUTH AMERICA

UCSF School of Medicine

 
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