Cervical cancer without HPV

Most studies confirm that 99% of cervical cancer are due to Human Papilloma viruses.   However, there is a small minority of cervical cancer that is not HPV related.   Recently, I operated on a 17 year old girl who is completely HPV negative.   I reviewed the literature and found that the youngest patient with non-HPV related cervical cancer was a 6 year old girl!   The rare type is clear cell adenocarcinoma rather than the usual squamous cell carcinoma (Usually HPV related).

HPV that causing cervical cancer are almost always transmitted through sexual contact.  The HPV require skin abrasion/injuries to allow them to penetrate to deeper skin layer so they can reproduce.  Chronic HPV infection, especially with high risk types HPV 16 and 18, are usually required to cause cancer (exception is shorter period required in immunosuppressed patients such as HIV infected or transplant patients).  This is why sexual abstinence and condoms reduce the risk of HPV infection.  However, clear cell cervical cancers do not seem to require HPV or sexual intercourse to cause cancer.

HPV vaccines are effective in reducing the risks of HPV related cervical, vaginal, vulvar and anal cancers.  Some patients have asked me if they could get HPV infection from the vaccines.   This is very very unlikely since the vaccines do not contain HPV.  The vaccines have the shell-like virus coat without HPV DNA.  I don't know any case report in the world that showing HPV vaccines causing HPV infection/cancer.   I highly recommend HPV vaccines for girls and boys to reduce these risks. 

Disclaimer: I am a speaker and consultant to Merck which makes one of the HPV vaccines.  

Sex and cancer diagnosis

Many patients of mine have told me that their cancer diagnosis turned their sexual interest down significantly.  It is very understandable for a sexually active couple to stop after seeing their gyn oncologists since their energy is focused on this new challenging diagnosis.   Furthermore, chemotherapy and surgery just wear you out to even thinking about this issue.

However, as time passes, there are physical changes that may affect your sexual health in the long term.  You may hear me saying that if you don't use it you lose it.   Similarly, vagina is like any other organs.  If you don't use it, especially when you become menopause due to surgery/radiation, your vagina tissue becomes less elastic and its diameter will narrow.  Sex may cause more pain and discomfort than before.  Do talk to your doctor about this and don't be embarrassed since many patients have similar questions that you do.  One of my patients, Michelle Witlock,  is very knowledgable and open about her experience going thru the extensive cancer treatment and how it affected her sexual life.  She gave me permission to share her website with you.  Do consider visiting her sites for informative stories: 

http://www.tamikaandfriends.org/get-support/ask-our-experts/sex-after-cancer

http://www.michelleleewhitlock.com/index.php

New biomarkers and ovarian cancer

Most people are aware about CA125 by now.  It is a blood test that measure our antibody responses to cancer antigen and it is called 125 because it was the 125th antibody against the studied ovarian cancer cell line.   It is elevated in about 80% patients with advanced ovarian cancer as well in other cancers such as uterine, cervix and others.  Unfortunately, it is also increases with other non-cancer conditions such as endometriosis, infection, inflammation, etc.  Therefore, CA125 is FDA-indicated only to measure tumor responses to chemotherapy, not to screen for ovarian cancer.

Another relatively new biomarker is HE4 blood test.  It is more specific than CA125 in that HE4 is not as elevated as CA125 in patients with endometriosis.   HE4 is also only indicated for cancer monitoring, not as screening.

Ova1 is a blood test measuring 5 different proteins which is put into one score to help surgeons to triage patients as low or high risk for ovarian cancer.   FDA cleared its usage for patients who are about to be operated for ovarian mass.   If the Ova1 test is abnormal, the test would suggest that gyn oncologist should be involved in the surgery.  In contrast, if the Ova1 test is normal, then the patient is at low risk for ovarian cancer and no gyn oncologist is needed to be involved.   Disclaimer: West Clinic was involved in the clinical study leading to the FDA approval of this test.

ROMA is another blood test combining CA125 and HE4 into one score.  ROMA is also FDA-cleared to be used like Ova1. Both Ova1 and ROMA are not indicated for ovarian cancer screening.

By now you may ask why don't any of these biomarkers be used to screen for ovarian cancer.  Unfortunately, no present test is currently has enough sensitivity and specificity to screen for a low prevalence disease like ovarian cancer (prevalence is 1 out of 2500 American women = 0.04%).   Even when we have a test with 100% sensitivity and 99% specificity, we only get about 4.8% of positive predictive value.  This means that this ideal test will only identify correctly one patient with ovarian cancer but falsely diagnosed 20 other patients who have no cancer as having ovarian cancer.   It is indeed a holly grail to find a better screening test.

Reference:

-Ueland, FR, et al. Obstet Gynecol 2011:VOL 117, NO. 6, June 2011

-ROMA® (HE4 EIA + Architect CA125 II™) Instructions For Use 2011-09, Fujirebio Diagnostics, Inc  

-Bast RC, et al.  Differential diagnosis of a pelvic mass.   Int Gyn Cancer. 2012

 

Drinking green tea and ovarian cancer

Green tea is the most widely used herbal product, used by 24 to 30 percent of all cancer patients.

   
Some suggested drinking a large amounts of green tea may improve survival in patients with ovarian cancer.  A Chinese study on 254 patients with ovarian cancer evaluated for 3 years in regards to survival and quantity of tea consumed. About 96% of patients were followed at the end of 3 year study period.  Statistical analysis were calculated to show a survival difference between tea drinkers and non-drinkers (p<0.001). There were 81 (77.9%) of 104 tea-drinkers who survived to the time of interview, compared to only 67 women (47.9%) still alive among the 140 non-drinkers.

Green tea can interact in a variety of ways with conventional cancer treatments.  The polyphenols in green tea inhibit multiple cytochrome p450 enzymes that are important in drug metabolism.  This enzymes work to degrade chemotherapy and other toxins that enter our bodies.  Consequently, green tea could increase the plasma concentrations of a variety of chemotherapeutic agents (for example Taxol, Taxotere, Adriamycin), possibly increasing drug toxicity. On the other hand, some drug-metabolizing enzymes are induced, which might lead to resistance to other chemotherapeutic agents.

In addition, preclinical studies suggest that the polyphenols contained in green tea may inhibit the induction of tumor cell death by the proteasome inhibitor bortezomib , which is used to treat multiple myeloma. While it is not clear that patients receiving this drug should refrain from drinking any green tea, it might be prudent to avoid ingesting large quantities, until further information is available.  Furthermore, do let your doctor know if you are drinking green tea since it may increase drug toxicities.

Reference:

-          Ernst E, et al.  Complementary and alternative therapies for cancer.  Uptodate. Sept 2012.

-     Dy GK, et al. Complementary and alternative medicine use by patients enrolled onto phase I clinical trials. J Clin Oncol. 2004;22(23):4810

-          Mei Y, et al.  Reversal of cancer multidrug resistance by green tea polyphenols. J Pharm Pharmacol. 2004;56(10):1307.

Can exercise reduces my risk of getting cancer?

In the world, there is an estimated 12.7 million cancer cases and 7.6 million cancer deaths worldwide.  In the United States, more Americans die from cancer than heart disease.  Obviously, many patients have asked me on ways to reduce the cancer risk.  I talked to you on my earlier blog of various ways.  On this page, I would like to discuss research on exercise and cancer prevention.

We know that about 60% of American adults are not active and 25% of them are completely sedentary.  A Harvard paper estimated that sedentary lifestyle is associated with 5 percent of cancer deaths.  A  study evaluated 79,771 Japanese adults in regards of cancer diagnosis and their activity levels.  The decreased risk was more clearly observed in women than in men, especially among the elderly and those who regularly engaged in leisure-time sports or physical exercise. By site, decreased risks were observed for cancers of the colon, liver, and pancreas in men and for cancer of the stomach in women. The author concluded that being active is beneficial in preventing cancer in a relatively lean population (Japanese have less obesity rate than Americans).  Some other studies suggest active life decreases breast and endometrial cancer rate.

How does exercise reduces cancer risk?.  It appeared that active life reduces circulating levels of insulin, hormones, and other growth factors (which are known to induce cancer growth); impact on prostaglandin levels; improved immune function, and altered bile acid metabolism.

Thus, now you have more reason to exercise.  Please talk to your health care provider first to make sure that you could exercise safely. At West Clinic where I work, the Wings organization has free exercise programs. please check their wellness program at http://www.westclinic.com/wings/

Reference:

- Inoue M, et al, Japan Public Health Center-based Prospective Study Group. Daily total physical activity level and total cancer risk in men and women: results from a large-scale population-based cohort study in Japan. Am J Epidemiol. 2008;168(4):391.

- Wolin KY, et al. Physical activity and colon cancer prevention: a meta-analysis.Br J Cancer. 2009;100(4):611

- Dallal CM, et al.Long-term recreational physical activity and risk of invasive and in situ breast cancer: the California teachers study. Arch Intern Med. 2007;167(4):408

I underwent hysterectomy, should I still get a pap smear?

It depends.   In general if you have your uterus and cervix removed for benign causes and you never had abnormal pap smear in the past, you don't have to get pap smear anymore.   You may still need a regular pap smear if:
- you had partial hysterectomy where the uterus was removed but your cervix was left in
- you had hysterectomy due to cervical cancer or dysplasia (abnormal cell growth in the cervix)
- you had history of abnormal pap smear before your hysterectomy
- your doctor or practitioner recommends it

The recommendation for routine pap smear has changed as well.  The starting age used to be 18 years old or 3 years after becoming sexually active.   Now most health organizations recommend starting pap smear at age 21 years old.  They did this knowing that there will be younger girls develop cervical cancer since the screening age is moved up.   Their reasoning is pap smear is to reduce number of cancer but will never eliminate it.  In the same time, pap smear at early age may increase surgery done in young girls.

The frequency of screening pap smear has also been changed from every year to every 2-3 years (from age 21 to 30 years old), then every 3-5 years with cotesting (pap smear + high risk HPV testing).

If you are confused, you are not alone since the guidelines keep on changing that even many doctors have difficulty keeping up with the changes.   There should be new recommendations coming from ASCCP and probably NCCN on pap smear probably in spring 2013.  Stay tune...

I am on chemo - should I get flu vaccine?

Our immune system protects us against illness and infection. Flu (influenza) vaccine works by inducing our body to generate antibodies against future infection from flu viruses.  However, in patients who are immunosuppressed (during chemotherapy, organ transplant, etc), our body may not be able to generate rigorous antibodies as compared when we were not immuno-suppressed.

However, patients who are immunosuppressed probably need the protection even more than healthy persons.  Thus, most oncologists recommend their patients to get flu vaccine knowing that the antibody responses may not be as good.  For most patients, the benefits are usually still outweigh the risks.   Do be aware, just like anything in medicine, there are side effects (fever, weakness, serious reaction, etc) that come with the vaccine.  Do discuss them with your oncologists since flu season is coming.

Chemo brain - is it real?

Some of my patients told me that they have "chemo brain".  They felt that they could not remember things as well and sometimes got disoriented.  Some reported that they were not as "sharp" as they used to.  

Out of curiosity, I investigated this and found a recent study reviewing 17 studies in 807 patients previously chemotherapy treated for breast cancer.  Neuropsychological tests were done to look at eight cognitive domains: attention, executive functioning, information processing, motor speed, verbal ability, verbal memory, visual memory, and visuospatial ability.  The study revealed that indeed patients treated with chemo (in contrast to control or prechemo baseline) performed worse in verbal and visuospatial abilities. Age, education, time since treatment, and endocrine therapy did not moderate these impairments.

Thus, Chemo brain indeed exists - at least in these patients.  

Reference:

Jim HS, Phillips KM, Chait S, et al. Meta-Analysis of Cognitive Functioning in Breast Cancer Survivors Previously Treated With Standard-Dose Chemotherapy. J Clin Oncol 2012.

what can I do to reduce my risks of getting cancer

My patients and friends often ask me on how to prevent cancer.  Many asked about the newest research they read or found in internet.   Unfortunately, many of those research are still in cell lines, animal studies or very early human studies.  Furthermore, many of these research would not yield its early promised.  I could vouch of this experience when my colleagues at UT Southwestern and I pioneered the first gene therapy in ovarian cancer in the world using adenovirus to reduce tumor growth.  Despite early promises and reaching a phase III study in human, the experiment did not go further due to excessive toxicities

But I have good news.   Actually there are things we know effectively prevent cancers.  However, I must warn you that these are not as exciting as what you read in the internet.   About 66% of cancer in the United States are related to smoking, overweight, poor diet, and inactivity. In one study, nine modifiable risks were identified as the cause of 35 percent of cancer deaths worldwide: smoking, alcohol, diet low in fruit and vegetables, excess weight, inactivity, unsafe sex, urban air pollution, use of solid fuels, and contaminated needles.

Thus, we could indeed reduce risks of cancer by one third (and other diseases too) by not smoking, maintain ideal body weight, active life and sensible diet.   Wow... If you published a study using a newly discovered pill to reduce cancer by 1/3, you would have been famous.  But in reality, we don't have that magic pill but we do have the power to reduce these cancer risks markedly by doing what our parents and teachers asked us to do.  Do be healthy and have a happy active life...

Reference:

·  Harvard Report on Cancer Prevention Volume 2: Prevention of Human Cancer. Cancer Causes and Control 1997; 8:S1.

·  Danaei G, Vander Hoorn S, Lopez AD, et al. Causes of cancer in the world: comparative risk assessment of nine behavioural and environmental risk factors. Lancet 2005; 366:1784.