Adenocarcinoma of the Uterine Cervix and HPV
Condition: Adenocarcinoma of the Uterine Cervix
MeSH terms: Adenocarcinoma
Study type: Observational

Summary: 
      The present study will mainly aim to review and characterize the pathologic features,
      treatment options, and follow-up outcomes of women with in situ/microinvasive adenocarcinoma
      of the uterine cervix according to HPV status (positive versus negative high-risk HPV). It
      will evaluate the impact of HPV status on the recurrence and survival during a follow-up of
      five years. The present study will be a multi-institutional study including several
      oncological Italian Centers. Data will be retrospectively collected from January 2012 to
      December 2016 with a total follow-up of 5 years.
    

Detailed description: 
      The incidence of cervical cancer in developed countries declined considerably in the last few
      decades. This has been possible for efficient screening programs to which HPV vaccines have
      been added over the past 15 years. Despite this global reduction in cervical lesions, the
      incidence of adenocarcinoma of the uterine cervix (AC) increases in invasive and in situ
      stages. This increase mainly affects women aged 30-40, with an incidence of 11.2 per 100.000
      women. On the contrary, the squamous histological lesions revealed an increase in the
      incidence of in situ lesions and a concomitant reduction of invasive stages. These data would
      seem to suggest a delay in the diagnosis of cervical glandular lesions, a shorter interval of
      disease progression from the adenocarcinoma in situ (AIS) to infiltrating stages, or a
      different process of carcinogenesis.

      Most glandular cervical lesions occur at an early stage. The standard of treatment for in
      situ or micro-invasive lesions is extra fascial hysterectomy (AIS or stage 1A1 with no LVSI)
      or modified radical hysterectomy with pelvic lymph node dissection (stage 1A1 with LVSI, or
      1A2). In fertility-sparing treatment, conization or radical trachelectomy with pelvic lymph
      node dissection is an option.

      Another aspect that differentiates cervical adenocarcinoma from squamous lesions is the link
      with HPV infection. In 2018, the International Endocervical Criteria and Classification
      categorized cervical glandular lesions into HPV-associated and non-HPV-associated AC. Unlike
      cervical squamous lesions, which are almost all linked to high-risk HPV types, AC can be HPV
      negative in up to 15-20% of cases. The HPV 18 genotype is the most represented in AC with a
      rate of 38-50% in AIS and 50% in invasive stages. Based on some studies, it appears that
      non-HPV-related lesions have worse outcomes. This can significantly impact screening programs
      where 14 high-risk HPVs are tested.

      In a recent study including 341 surgical specimens of AC, 100% of non-HPV-related lesions
      were classified as Silva Pattern C (the worst prognostic pattern). Instead, no impact of the
      HPV genotype was found on 113 women with AC during a follow-up of 5 years. HPV 45 showed a
      shorter 5-year survival than HPV 16 or 18.

      While for advanced lesions, the stage itself represents the most important prognostic factor
      for prognosis, in situ or micro-invasive lesions may represent the best target for evaluating
      HPV status impact. This may be of interest as there is the option of conservative treatment
      in addition to standard treatment in early stages.
    

Intervention name(s): Conization and/or Hysterectomy
Intervention type(s): Procedure
Intervention description(s): Women undergoing cervical conization or simple/modified/radical hysterectomy with or without pelvic lymphadenectomy
Observational model: Case-Only
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        All women who were diagnosed with in situ or microinvasive (stage 1 A) adenocarcinoma of
        the uterine cervix, and undergoing surgical treatment, between 2012 and 2016.
      
Keywords: Cervical Adenocarcinoma; HPV Type; Screening Program; Treatment; Recurrence; Survival; Follow-up