[Question #6926] ASC-US and +HPV cancer risk

11 months ago
My wife is 3 months pregnant and went for her PAP/HPV testing in April 2020. She is 42 and has always been receiving PAP and HPV screenings as per her doctor's recommendations. She has never had an abnormal PAP or positive HPV result. Her last test before this year was on 3/11/19 with a NORMAL PAP and NEGATIVE for HR HPV. 
On her most recent tests in April 2020, she received the following results:
2. HPV RNA HR E6/E7, TMA:  Value = "Detected", Ref Range = "Not Detected"
3. HPV GENOTYPE 16 & 18:   Value = "Not Detected", Ref Range = "Not Detected"

Her doctor ordered a Colposcopy next month, plus a biopsy if necessary but didn't give us much additional info. She has never had sex with anyone before me. However, I had multiple partners in the past. I'm certain I gave her HPV because we started having sex 6 months ago. These are her first abnormal test results. We are both quite nervous. 
My questions are:

1. Given her history and recent test results, what are the chances that Cervical Cancer has already developed/will develop quickly?
2. What does the "HPV RNA HR E6/E7, TMA" test mean since she tested NEGATIVE for HPV 16 and 18?
3. On her HPV RNA HR E6/E7 results, the Value was "Detected" but the Ref Range was "Not Detected". what does this mean?
4. Lastly, her HPV 16/18 test has the comment: "The assay can differentiate HPV 16 from HPV 18 and/or HPV 45, but does not differentiate between HPV 18 and HPV 45" What does this mean?

Thank you doctor!
Edward W. Hook M.D.
Edward W. Hook M.D.
11 months ago
Welcome to our Forum.  Thanks for your question.  I’ll do my best to help although for most of the decision making I would urge your wife to work with her OB to determine the way forward.

Pregnancy has many effects on the immune system and warts and thus presumably HPV can reactivate or become more apparent with pregnancy.  With a newly positive PAP, colposcopy would be a logical next step.  In many instances the colposcopy shows changes and biopsy is not required.  In answer to your specific questions:

1.  Typically it takes years or even decades for the small proportion of HPV infections that progress to cancer to do this.  The term ASCUS means Atypical Squamous Cells of Uncertain Significance and while further evaluation is warranted, it would be unusual for this grade of abnormality to indicate cancer.  Often ASCUS will even resolve on its own.

2.  There are a number of HPV types which are associated with somewhat increased risk for cancer.  While types 16 and 18 are among the most common types, there are other HPV types also associated with elevated cancer risk.  The E6/E7 proteins are likewise associated as co-factors with risk for cancer.  This is why the colposcopy is warranted.

3.  “Detected”simply means that the test for E6/E7 was positive.

4.  This result means that the test results do not tell you what HPV type is present but do indicate that the type present is not HPV 16.

Please understand that interpreting these test results can be confusing. Once again these are the sorts of things which you and your wife would best discuss with her obstetrician. I hope that my responses are some help. EWH
11 months ago
Dr. Hook, thank you for your responses. They were very helpful. Just had a couple follow up questions: 

1. Are E6/E7 proteins always present with HR HPV? Do they present an "additional" cancer risk on top of the HR HPV?

2. So, the chances of first time ASC-US with +HR HPV rarely turn out to be cancer upon completion of a Colposcopy, correct?

3. Referring to your answer to question #4, I understand she doesn't have HPV 16. Her test results also came back NEGATIVE for HPV18. Given the disclaimer "does not differentiate between HPV 18 & 45", does this mean they're not sure if she's NEGATIVE for 18? Or, is she negative for either 18 or 45 but they don't know which?

I attached the test results. Sorry if the last question was confusing. 

Thanks again!
Edward W. Hook M.D.
Edward W. Hook M.D.
11 months ago
1.  No, they are not always present and when present are associated with a somewhat increased risk.  The risk however remains relatively low.
2.  Correct.
3.  The last question is a bit confusing but, as I read it, her test is negative for 16, 18, and 45 but, as I said earlier, you should really be discussing this with her OB/GYN.

10 months ago
Dr. Hook, thank you for your replies. I believe I have 1 more follow up question left. 

In reference to my original question #2 for the E6/E7 test, the Value says "Detected" and the Reference Range says "Not Detected". My question is: What does it mean for the Reference Range to be "NOT DETECTED"? 

Thank you for your help and we are following up with her OB as scheduled. 
Edward W. Hook M.D.
Edward W. Hook M.D.
10 months ago
Laboratories certainly do make it difficult to understand their results, don’t they. The reference, or normal/preferable result of a test to E6/E7 RNA is that it be not present/detectable.  I your wife’s specimen, E6/E7 RNA was detected.

I hope that my responses have been somewhat helpful to you and your wife. It is now however time for you to seek further answers and discuss this with your obstetrician gynecologist. As you note this is my final response to this thread. The thread will be closed shortly without further responses. Take care. EWH