Question

A 36-year-old woman attends the emergency department with worsening light-headedness and ongoing vaginal bleeding after intercourse earlier that evening. She reports repeated episodes of bleeding after sex over the past year. She has had multiple previous sexual partners and inconsistent condom use. She smokes, drinks occasionally, has gained weight, and has a past history of genital herpes.

On speculum examination, there is active bleeding from a visibly abnormal cervix. She is urgently referred to gynaecology with suspected cervical malignancy.

Which of the following factors is most likely to have made the greatest contribution to the development of her condition?

A. Progesterone-only implant
B. Increased body weight
C. Smoking
D. Previous genital herpes infection
E. Human papillomavirus type 2 infection

Answer

C. Smoking

Detailed explanation

This patient has features strongly suggestive of cervical cancer:

• Postcoital bleeding
• Recurrent abnormal vaginal bleeding
• Visible abnormal cervix
• Active cervical bleeding
• Risk factors such as smoking and previous high-risk sexual exposure

The single most important cause of cervical cancer overall is persistent infection with high-risk human papillomavirus, especially HPV 16, 18 and 33.

However, the option given here is HPV type 2, not HPV 16 or 18. HPV 2 is classically associated with common cutaneous warts, especially on the hands, and is not a major cervical carcinogenic strain.

Among the options provided, smoking is therefore the best answer. Women who smoke have approximately a two-fold increased risk of cervical cancer compared with non-smokers. Smoking is thought to impair local cervical immune defence and may allow persistence of oncogenic HPV infection. Tobacco-related carcinogens can also be detected in cervical mucus.

Why the other options are wrong

A. Progesterone-only implant
Progesterone-only contraception, such as the contraceptive implant, is not a major established risk factor for cervical cancer. Combined oral contraceptive use has been associated with a small reversible increase in cervical cancer risk, especially with prolonged use, but that is not the same as a progesterone-only implant.

B. Increased body weight
Obesity is a risk factor for several malignancies, especially endometrial, breast, colorectal and oesophageal adenocarcinoma. It is not one of the strongest direct risk factors for cervical cancer. Some association may be partly related to reduced screening uptake or technical difficulty with cervical screening.

C. Smoking
This is correct. Smoking roughly doubles cervical cancer risk and is an established modifiable risk factor. In exam questions, smoking is important when high-risk HPV is not listed as an option.

D. Previous genital herpes infection
HSV-2 causes genital herpes but is not regarded as a direct cause of cervical cancer. It may coexist with other sexually transmitted infections because of shared sexual risk factors, but HSV itself is not the key carcinogenic infection.

E. Human papillomavirus type 2 infection
HPV is central to cervical cancer pathogenesis, but the important types are high-risk HPV strains, especially 16, 18 and 33. HPV 2 is mainly associated with common skin warts and is not a major cervical cancer strain. This is the trap in the question.

Key exam point

High-risk HPV, especially types 16, 18 and 33, is the most important cause of cervical cancer, but if the option says HPV 2, do not choose it. HPV 2 causes common warts, not cervical cancer. In this question, smoking is the best answer.

Very important clinical trap

Do not answer “HPV” automatically without checking the subtype.

HPV 16 and 18: high-risk cervical cancer strains.
HPV 6 and 11: genital warts, low malignant potential.
HPV 2: common skin warts, not an important cervical cancer strain.

Cheat sheet for exam

• Cervical cancer commonly presents with:
  • Postcoital bleeding
  • Intermenstrual bleeding
  • Postmenopausal bleeding
  • Offensive or persistent vaginal discharge
  • Abnormal cervix on speculum examination
• Main histological types:
  • Squamous cell carcinoma: about 80%
  • Adenocarcinoma: about 20%
• Most important cause:
  • Persistent high-risk HPV infection
• High-risk HPV types:
  • HPV 16
  • HPV 18
  • HPV 33
• Low-risk HPV types:
  • HPV 6 and 11 cause genital warts
• HPV 2:
  • Common cutaneous warts
  • Not a major cervical cancer strain
• Other cervical cancer risk factors:
  • Smoking
  • HIV/immunosuppression
  • Early age at first intercourse
  • Multiple sexual partners
  • High parity
  • Lower socioeconomic status
  • Long-term combined oral contraceptive use
• Smoking:
  • Approximately doubles cervical cancer risk
  • Modifiable risk factor
  • Promotes persistence of high-risk HPV and local carcinogenic changes
• HPV oncogenesis:
  • E6 inhibits p53
  • E7 inhibits retinoblastoma protein, Rb

Flash cards

Q: What is the most important cause of cervical cancer?
A: Persistent infection with high-risk HPV, especially HPV 16 and 18.

Q: Which HPV types are most associated with cervical cancer?
A: HPV 16, 18 and 33.

Q: Which HPV types cause genital warts?
A: HPV 6 and 11.

Q: What disease is HPV 2 classically associated with?
A: Common cutaneous warts, particularly palmar or skin warts.

Q: How much does smoking increase cervical cancer risk?
A: Approximately two-fold compared with non-smokers.

Q: What are classic presenting symptoms of cervical cancer?
A: Postcoital bleeding, intermenstrual bleeding, postmenopausal bleeding and abnormal vaginal discharge.

Q: Which HPV oncogene inhibits p53?
A: E6.

Q: Which HPV oncogene inhibits Rb?
A: E7.

Q: Does HSV-2 directly cause cervical cancer?
A: No. HSV-2 causes genital herpes but is not a direct major cervical cancer risk factor.

Q: Is the progesterone-only implant a major risk factor for cervical cancer?
A: No. Long-term combined oral contraceptive use has a debated/small association, but progesterone-only implant use is not a key risk factor.

MCQs

1. A 31-year-old woman presents with recurrent postcoital bleeding. Examination reveals a friable abnormal cervix. Which HPV type is most strongly associated with cervical cancer?

A. HPV 2
B. HPV 6
C. HPV 11
D. HPV 16
E. HPV 1

Answer: D. HPV 16

Explanation: HPV 16 is one of the highest-risk HPV types for cervical cancer. HPV 18 and 33 are also important. HPV 6 and 11 cause genital warts and have low malignant potential. HPV 2 is associated with common skin warts.

2. Which of the following is false regarding cervical cancer?

A. Smoking increases the risk
B. HPV 16 is a high-risk oncogenic strain
C. HPV E6 inhibits p53
D. HPV 2 is a major cause of cervical cancer
E. Postcoital bleeding is a common presenting symptom

Answer: D. HPV 2 is a major cause of cervical cancer

Explanation: This is false. HPV 2 is associated with common cutaneous warts. Cervical cancer is mainly associated with persistent high-risk HPV infection, especially HPV 16, 18 and 33.

3. Which symptom is most classically associated with cervical cancer?

A. Cyclical pelvic pain relieved by menstruation
B. Postcoital bleeding
C. Profuse frothy green discharge only
D. Primary amenorrhoea
E. Acute urinary retention

Answer: B. Postcoital bleeding

Explanation: Cervical cancer commonly presents with abnormal vaginal bleeding, especially postcoital bleeding. It can also present with intermenstrual or postmenopausal bleeding and vaginal discharge.

4. A woman with suspected cervical cancer asks how smoking contributes to the disease. Which explanation is most accurate?

A. Smoking directly causes HPV 2 infection
B. Smoking prevents cervical ectropion from healing
C. Smoking increases cervical cancer risk, partly by impairing local immunity and promoting HPV persistence
D. Smoking only increases endometrial cancer risk
E. Smoking protects against cervical adenocarcinoma but not squamous carcinoma

Answer: C. Smoking increases cervical cancer risk, partly by impairing local immunity and promoting HPV persistence

Explanation: Smoking is an established modifiable risk factor for cervical cancer and approximately doubles risk. It may promote persistence of high-risk HPV and expose cervical tissue to carcinogenic substances.

5. Which HPV-related mechanism contributes to cervical carcinogenesis?

A. E6 activates BRCA1
B. E7 stimulates p53 repair activity
C. E6 inhibits p53 and E7 inhibits Rb
D. E6 suppresses oestrogen receptors only
E. E7 activates mismatch repair proteins

Answer: C. E6 inhibits p53 and E7 inhibits Rb

Explanation: High-risk HPV strains produce oncogenic proteins. E6 inhibits the p53 tumour suppressor pathway, while E7 inhibits the retinoblastoma tumour suppressor pathway.

6. Which of the following is most strongly associated with genital warts rather than cervical cancer?

A. HPV 16
B. HPV 18
C. HPV 33
D. HPV 6
E. HIV

Answer: D. HPV 6

Explanation: HPV 6 and 11 are low-risk strains that cause genital warts. HPV 16, 18 and 33 are high-risk cervical cancer-associated strains.

7. Which of the following is false regarding risk factors for cervical cancer?

A. HIV infection increases risk
B. Multiple sexual partners increase risk
C. Smoking increases risk
D. High-risk HPV infection increases risk
E. HSV-2 is the main direct cause of cervical cancer

Answer: E. HSV-2 is the main direct cause of cervical cancer

Explanation: HSV-2 causes genital herpes but is not the main direct cause of cervical cancer. Persistent high-risk HPV infection is the key driver.

8. A 42-year-old woman has abnormal cervical screening and high-risk HPV is detected. Which tumour suppressor protein is inhibited by HPV E7?

A. p53
B. Rb
C. APC
D. PTEN
E. VHL

Answer: B. Rb

Explanation: HPV E7 inhibits the retinoblastoma protein, Rb. HPV E6 inhibits p53. This distinction is a common exam favourite.

9. Which contraceptive-related statement is most accurate for cervical cancer risk?

A. Progesterone-only implant is the strongest contraceptive risk factor
B. Copper coil use is the main cause of cervical cancer
C. Long-term combined oral contraceptive use has been associated with a small reversible increase in risk
D. Barrier contraception increases cervical cancer risk
E. Emergency contraception causes cervical cancer

Answer: C. Long-term combined oral contraceptive use has been associated with a small reversible increase in risk

Explanation: The combined oral contraceptive pill has been associated with a small increased risk of cervical cancer, which appears to reduce after stopping. Progesterone-only implant use is not a major established risk factor.

10. A patient has HPV 2 detected from a hand wart. She is worried about cervical cancer. Which statement is most appropriate?

A. HPV 2 is the most oncogenic cervical strain
B. HPV 2 mainly causes common skin warts and is not a major cervical cancer strain
C. HPV 2 causes most adenocarcinomas of the cervix
D. HPV 2 is equivalent in risk to HPV 16
E. HPV 2 always requires colposcopy

Answer: B. HPV 2 mainly causes common skin warts and is not a major cervical cancer strain

Explanation: HPV 2 is associated with common cutaneous warts. Cervical cancer is associated with high-risk HPV strains such as 16, 18 and 33.

Summary for quick exam revision

Cervical cancer should be suspected in women with postcoital bleeding, intermenstrual bleeding, postmenopausal bleeding, abnormal discharge or a visibly abnormal cervix. The most important cause is persistent infection with high-risk HPV, especially types 16, 18 and 33. HPV 16 and 18 drive malignancy through viral oncogenes: E6 inhibits p53 and E7 inhibits Rb. HPV 6 and 11 cause genital warts and are low-risk strains. HPV 2 causes common skin warts and is not a major cervical cancer strain, making it a classic exam trap. Smoking is an established modifiable risk factor for cervical cancer and approximately doubles the risk. Smoking may impair local cervical immune defence and promote persistence of oncogenic HPV infection. Other risk factors include HIV, immunosuppression, early first intercourse, multiple sexual partners, high parity, lower socioeconomic status and long-term combined oral contraceptive use. Progesterone-only implant use is not a major cervical cancer risk factor. HSV-2 causes genital herpes but is not a direct major cause of cervical cancer. Obesity is not among the strongest direct risk factors for cervical cancer, although it may reduce screening uptake. The two main histological types are squamous cell carcinoma, which is more common, and adenocarcinoma. In an exam, if the option is high-risk HPV, choose HPV as the strongest risk factor; if the option is HPV 2, do not choose it. In that situation, smoking is the best answer.